TYSABRI® (natalizumab) COVERAGE AND REIMBURSEMENT

TYSABRI® (natalizumab) COVERAGE AND REIMBURSEMENT

Please see full Prescribing Information, including Boxed Warning, as well as Important Safety Information about TYSABRI on pages 66-70. DECISIVE ACTION MATTERS

Prescribing TYSABRI

Ordering TYSABRI

Claims Information for TYSABRI

Patient Support

Healthcare Reform

Important Safety Information

FAQs and Glossary

TYSABRI (natalizumab) COVERAGE AND REIMBURSEMENT Biogen™ is committed to providing support on behalf of patients with relapsing multiple sclerosis (RMS) who are prescribed TYSABRI® therapy. This document is designed to provide information materials that can help practice administrators and other key practice staff understand the various aspects of the administrative needs and reimbursement process for TYSABRI. In addition, this document contains links to sample forms that illustrate how to meet specific health plan requirements. 1

HOW TO USE YOUR TYSABRI COVERAGE AND REIMBURSEMENT GUIDE

2

1

The main sections are listed across the top of the document and enable you to move from one section to the next.

2

On the main page of each section, you will find a list of the contents that that section comprises. You can simply click on the information you wish to view and go right to that page. Additional information or support material can be found through the www.TYSABRIHCP.com site. To find this information, links with this symbol will take you there.

The information is intended for informational purposes only and does not represent legal or billing advice. For specific guidance in this area, consult your own legal/billing advisor and billing/coding specialist, because it remains your responsibility to ensure the accuracy of the claims your office submits. The content here is based on information current as of June 2015 and may have changed. Any product, ancillary supplies, or services received free of charge cannot be billed to third-party payers, because doing so could be a violation of federal and/or state laws and/or third-party–payer requirements.

Please see full Prescribing Information, including Boxed Warning, as well as Important Safety Information about TYSABRI on pages 66-70. -2-

DECISIVE ACTION MATTERS

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TYSABRI (natalizumab) COVERAGE AND REIMBURSEMENT

FAQs and Glossary

Important Safety Information

(CONT’D)

Additional Help:

FINANCIAL & INSURANCE SUPPORT IS AVAILABLE TO HELP WITH QUESTIONS REGARDING A PATIENT’S HEALTH PLAN COVERAGE FOR TYSABRI® AND CAN CONNECT YOU WITH AN INFUSION REIMBURSEMENT ACCOUNT MANAGER, WHEN NEEDED:

1-800-456-2255

Please see full Prescribing Information, including Boxed Warning, as well as Important Safety Information about TYSABRI on pages 66-70. -3-

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PRESCRIBING TYSABRI (natalizumab) The TOUCH® Prescribing Program and Enrollment Process Understanding Insurance Coverage for TYSABRI® Completing a Prior Authorization or Pre-Certification Requesting a Medical Exception

Please see full Prescribing Information, including Boxed Warning, as well as Important Safety Information about TYSABRI on pages 66-70.

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THE TOUCH PRESCRIBING PROGRAM Due to the risk of progressive multifocal leukoencephalopathy (PML), TYSABRI® (natalizumab) is available only through the TOUCH® Prescribing Program, which stands for TYSABRI Outreach: Unified Commitment to Health. Prescribers should educate patients on the benefits and risks of treatment with TYSABRI, ensure that patients receive the Medication Guide, and encourage them to ask questions. The TOUCH Prescribing Program restricts the availability of TYSABRI to certified prescribers, infusion sites, pharmacies, and patients enrolled in the program.

The TOUCH Prescribing Program was designed to:

Inform

Warn

Promote

prescribers, infusion sites, and patients about the risk of PML associated with TYSABRI, including the increased risk of PML with longer treatment duration, prior immunosuppressant use, and the presence of John Cunningham virus (JCV) antibodies

against concurrent use with antineoplastic, immunosuppressant, or immunomodulating agents and in patients who are immunocompromised

early diagnosis of PML and timely discontinuation of TYSABRI in the event of suspected PML

Remember, patients can receive TYSABRI through only a TOUCH-authorized infusion site. For a comprehensive list of TOUCHauthorized sites, click here Infusion Site Locator. The Biogen Infusion Reimbursement Account Manager team will work with you to locate additional TOUCH-authorized sites so that your patients have options. The Infusion Reimbursement Account Manager team can potentially train and authorize the site based upon established criteria.

Please see full Prescribing Information, including Boxed Warning, as well as Important Safety Information about TYSABRI on pages 66-70. -5-

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THE TOUCH PRESCRIBING PROGRAM ENROLLMENT PROCESS Getting Started in the TOUCH Prescribing Program The first step to getting a patient started on TYSABRI® (natalizumab) is to review, complete, and sign the TOUCH® Prescribing Program Prescriber/ Patient Enrollment Form pictured below. To learn more about enrolling in the TOUCH Prescribing Program, contact a Support Coordinator from Above MS™ at Biogen™, by calling toll free: 1-800-456-2255.

For more information on the TOUCH Prescribing Program, please click below to visit TOUCH On-Line. TOUCH Prescribing Program

If your office has questions about the TOUCH Prescribing Program Prescriber/Patient Enrollment form, please contact a Support Coordinator from Above MS at 1-800-456-2255 Monday through Friday from 8:30 am to 8:00 pm (ET).

Please see full Prescribing Information, including Boxed Warning, as well as Important Safety Information about TYSABRI on pages 66-70. -6-

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THE TOUCH PRESCRIBING PROGRAM ENROLLMENT PROCESS (CONT’D) Your office and the patient will receive a Notice of Patient Authorization (pictured to the right) to confirm enrollment in the TOUCH® Prescribing Program. This is specific to the TOUCH Prescribing Program and is NOT an indication of insurance coverage. Upon completing the FIRST TOUCH Prescribing Program Prescriber/Patient Enrollment Form, a provider will receive a TOUCH ID. This alphanumeric code is your unique identifier as a participant in the TOUCH Prescribing Program, and it may be referenced by Biogen™ or pharmacies as part of communication about program compliance or ordering TYSABRI® (natalizumab). Each patient will also be assigned a unique TOUCH ID as part of enrollment in the TOUCH Prescribing Program. This alphanumeric code will be on the Notice of Patient Authorization that notifies providers that a patient is authorized to receive TYSABRI. Only authorized patients may receive TYSABRI, and TYSABRI may be administered only at TOUCHauthorized infusion sites.

Sample Notice of Patient Authorization

Please see full Prescribing Information, including Boxed Warning, as well as Important Safety Information about TYSABRI on pages 66-70. -7-

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UNDERSTANDING INSURANCE COVERAGE Benefit Investigation Once your office and the patient are enrolled in the TOUCH® Prescribing Program, the next step is to determine the patient’s drug and medical coverage. Payers have different requirements for coverage, and it is important to know the key clinical and coverage criteria. This information is acquired through a Benefit Investigation. If requested on the TOUCH Prescribing Program Prescriber/Patient Enrollment form, a Benefit Investigation can be conducted by Above MS™ support coordinators. A Benefit Investigation helps clarify patient coverage including any Prior Authorization or Pre-Certification, step therapy, or Pre-Determination requirements set forth by a patient’s payer. Most patients will have either a copay or coinsurance responsibility for the drug and the administration of TYSABRI® (natalizumab).

To discuss a patient’s Above MS Benefit Investigation, your office can contact a Support Coordinator from Above MS by calling 1-800-456-2255.

Please see full Prescribing Information, including Boxed Warning, as well as Important Safety Information about TYSABRI on pages 66-70. -8-

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Important Safety Information

BENEFIT INVESTIGATION FOR TYSABRI (natalizumab) If the patient is going to be infused in the office, your office will be asked to select one of 3 choices on the TOUCH® Prescribing Program Prescriber/ Patient Enrollment Form: 1

2

3

When filling out the TOUCH Prescribing Program Prescriber/Patient Enrollment Form, your office will need to indicate where the patient is going to be infused and what services may be required.

1

“No services required”

2

“ Forward this prescription to a specialty pharmacy provider to investigate pharmacy coverage and coordinate delivery to prescriber’s office”

This means that Above MS™ will provide no further services. Your office would select this if there are no questions regarding patient coverage or if you prefer to do the Benefit Investigation yourself.

Above MS will forward the prescription to a specialty pharmacy, and will not conduct a Benefit Investigation. The specialty pharmacy will conduct a benefit investigation and will generally communicate benefits directly to the patient.

3

“Please conduct insurance research and procurement options for TYSABRI” Upon receiving the TOUCH Prescribing Program Prescriber/Patient Enrollment Form, Above MS will conduct a Benefit Investigation and send a completed Summary of Benefits to your office.

Please see full Prescribing Information, including Boxed Warning, as well as Important Safety Information about TYSABRI on pages 66-70. -9-

DECISIVE ACTION MATTERS

Prescribing Prescribing TYSABRI TYSABRI

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BENEFIT INVESTIGATION FOR TYSABRI (natalizumab)

Healthcare Reform

Important Safety Information

FAQs and Glossary

(CONT’D)

If your office is referring the patient to an infusion site or if it requests the TOUCH®Prescribing Program’s help in locating an infusion site, then your office will not be conducting a Benefit Investigation. Above MS™ will reach out to the infusion site to find out if they would like Above MS to investigate benefits. If the infusion site requests that Biogen™ conduct a Benefit Investigation, your office will receive a completed Summary of Benefits for your records. The TYSABRI® Benefit Investigation Worksheet (pictured right) can assist your office with an in-office Benefit Investigation. It goes through the steps of gathering the necessary information from the patient’s payer. A list of possible health plan restrictions can be found on the next page. Restrictions are requirements that your patient and your office must fulfill before the health plan will agree to cover the cost of TYSABRI.

BENEFIT INVESTIGATION WORKSHEET FOR TYSABRI® (natalizumab) – INSTRUCTIONS

Step 1: For expediency, complete basic patient information before calling insurance company. Patient Name: ___________________________ Date of Birth: ____/____/______

Policy Holder Name: _________________________

Insurance Company Name: ______________________________________________________

Phone Number: ___________________

Member #: _______________________

Group #: _______________________ Plan Type:

HMO

Insurance:

Tertiary Is there a secondary policy:

In Network:

Primary

Secondary

Yes

No

PPO

POS Yes

Other________ No

Physician Name/Site of Care: ___________________________ Tax ID: ______________________ Provider #: ____________________

Step 2: Be sure to capture basic call details for easier follow-up. Researched date: ____/____/____ Time:__________ Person(s) you spoke with:___________________________________________ Policy year is:

Calendar

Benefit

Effective date: ____/____/______

Termination date: ____/____/______

Diagnosis: 340 NDC Code: 64406-0008-01 Unique Drug Code: J2323 Procedure Code: 96413 Billing Preference: _____________

Step 3: Carefully assess patient benefit options to find the best fit for you and your patient. When TYSABRI is covered under the medical benefit, patients may have the option of physician purchase and bill or specialty pharmacy (AOB). Other patients will have only one option available to them. It is possible that some patients will not be covered under either Major Medical option. In that case, coverage under the patient’s pharmacy benefit should be investigated. Infusion Administration Benefit (The physician bills for the infusion and receives reimbursement from the health plan)

Outcome:

Covered

TYS covered:

Not Covered —

Deductible:

Enter amount: $

Deductible met:

Enter amount: $

Out-of-pocket maximum: Out-of-pocket maximum met: Lifetime maximum:

Specialty Pharmacies in network*

Drug Copay / Coinsurance:

Specialty Pharmacy Option Through Major Medical Benefit

Specialty Pharmacy Option Through Prescription Drug Benefit

(The site of care purchases TYSABRI, bills for the drug, and receives reimbursement from the health plan)

(Benefits are assigned to a network specialty pharmacy. The specialty pharmacy bills for the cost of TYSABRI)

(TYSABRI is covered under the pharmacy benefit. The specialty pharmacy bills for the cost of TYSABRI)

Covered Yes:

Not Covered

No:

Enter amount: $

Enter amount: $

Enter amount: $

Enter amount: $

—

Enter % or $ amount:

—

Enter % or $ amount:

Includes Deductible

Not Covered

No:

Enter amount: $ Enter amount: $

Enter amount: $ Excludes Deductible

Covered Yes:

Enter amount: $

Enter amount: $ Includes Deductible

Not Covered

No:

Enter amount: $

Enter amount: $ Excludes Deductible

Covered Yes:

Enter amount: $

Enter amount: $ Includes Deductible

Physician Purchase Option Through Major Medical Benefits

Enter amount: $ Excludes Deductible

Includes Deductible

Enter amount: $

Enter amount: $

Enter amount: $

Enter amount: $

Name:

Name:

Phone #:

Phone #:

Name:

Excludes Deductible

Name:

Phone #:

Phone #:

Name:

Name:

Phone #:

Phone #:

Enter % or $ amount:

Enter % or $ amount:

Pharmacy cap:

—

—

Enter amount: $

Enter amount: $

Pharmacy cap met:

—

—

Enter amount: $

Enter amount: $

Enter any important details here

Enter any important details here

Enter any important details here

Enter any important details here

Additional Benefit Information:

Please see Full Prescribing Information, including Boxed Warning, as well as Important Safety Information about TYSABRI on pages 9-11.

Benefit Investigation Worksheet

Please see full Prescribing Information, including Boxed Warning, as well as Important Safety Information about TYSABRI on pages 66-70. - 10 -

DECISIVE ACTION MATTERS

Prescribing Prescribing TYSABRI TYSABRI

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BENEFIT INVESTIGATION FOR TYSABRI (natalizumab)

Healthcare Reform

FAQs and Glossary

Important Safety Information

(CONT’D)

When conducting a Benefit Investigation, suggested specific items to research are: Prior Authorization and required documentation

Step Edit

• Does the patient need

• Does the payer require

approval from the payer before receiving TYSABRI treatment, in order for it to be covered?

prior usage of one or more MS therapies before TYSABRI can be used?

• Does the payer require specific documentation— for example, Letter of Medical Necessity, package insert, FDA approval letter, pricing sheet, and clinical reprint—before approving?

• It is important to determine how each payer defines “failure” on an MS drug, for example, 6 months on therapy

Medical Exception

• If the payer does not cover TYSABRI or if it denies coverage, then your office can seek a Medical Exception

Acquisition requirements

• Does the payer require your office to acquire TYSABRI from a designated specialty pharmacy?

• Each payer has a

Coding and claims submission details

Patient financial responsibility

• When submitting a

• Depending on the

claim to the insurance company, your office will need to use the appropriate billing codes

patient’s payer, the copay and deductible may vary

different policy for handling Medical Exceptions

Please see full Prescribing Information, including Boxed Warning, as well as Important Safety Information about TYSABRI on pages 66-70. - 11 -

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ABOVE MS™ BENEFIT INVESTIGATION Above MSTM by Biogen™ has a service that helps patients gain access to their Biogen relapsing MS medication. In addition to performing the Benefit Investigation, a Support Coordinator from Biogen can follow up with the patient’s payer to ensure that any Prior Authorization or Step Edit requirements have been completed and approved before the patient initiates therapy. Also, Above MS offers personalized assistance to identify the best financial assistance option for your patients, including a copay assistance program for eligible patients. The goal is to ensure that no one forego Biogen treatment based solely on financial limitations. If your office requests a Benefit Investigation through the TOUCH® Prescribing Program Prescriber/Patient Enrollment Form, a Support Coordinator from Above MS will conduct the necessary Benefit Investigation, including: Researching patient’s insurance coverage for TYSABRI® (natalizumab) and providing a Summary of Benefits to your office

Working with patient’s insurance company to coordinate coverage through a specialty pharmacy when needed

Ensuring Prior Authorization and Pre-Certification requirements are met

To successfully complete a Benefit Investigation, Biogen requires the following information from your office to determine if the patient’s benefits will be considered in or out of network: 1. Your payer-specific provider ID # 1 2. Your Tax ID # 2 3. Whether you use the CMS-1500 Form for Physician Office Billing or the CMS-1450/UB-04 Form for Hospital Outpatient Billing 3 If the required information is not on file, a Support Coordinator from Biogen will contact your office to obtain the information. When this information is on file, a Support Coordinator may check in periodically to ensure that the information has not changed.

Please see full Prescribing Information, including Boxed Warning, as well as Important Safety Information about TYSABRI on pages 66-70. - 12 -

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ABOVE MS™ BENEFIT INVESTIGATION (CONT’D) Once Above MS™ researches the patient’s insurance benefits, a Support Coordinator from Biogen™ will send your office and the infusion site of care (if different) a patient-specific Summary of Benefits. This Summary of Benefits can also be viewed at TOUCH® On-Line. A sample Summary of Benefits can be found on the next page. The Summary of Benefits contains 3 sections:

1

Patient Information: The patient’s information, including insurance, and infusion administration benefit

2

3

Benefit Details: Infusion: The coverage that a patient has for the administration of TYSABRI® (natalizumab) Buy-and-Bill Option: The purchasing option that the payer will cover through the medical benefit if a provider purchases TYSABRI and submits a claim to the payer for reimbursement

Prior Authorization Requirements: Any Prior Authorization or step-therapy requirements that a provider or administration site must complete to help a patient gain access to therapy

Specialty Pharmacy Assignment of Benefits Option: The purchasing options that the payer will cover through the medical benefit with the drug shipped to the provider through an authorized TYSABRI Specialty Pharmacy  pecialty Pharmacy Prescription Drug Benefit Option: S The purchasing options that the payer will cover through prescription drug benefit with the drug shipped from the specialty pharmacy to the provider The Summary of Benefits is NOT a Pre-Certification or guarantee of payment, is not guaranteed by Biogen to be accurate, and should be used as guidance only. It is the responsibility of the infusion site, before each infusion, to confirm that coverage for the patient has not changed.

Please see full Prescribing Information, including Boxed Warning, as well as Important Safety Information about TYSABRI on pages 66-70. - 13 -

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SAMPLE SUMMARY OF BENEFITS Patient Insurance Overview 1 Patient Information

Determine Prior Authorization and Documentation Requirements 3 Prior Authorization Requirements

Determine Access Restrictions and Purchasing Options 2 Benefit Details

Sample Summary of Benefits The Summary of Benefits is NOT a Pre-Certification or guarantee of payment, is not guaranteed by Biogen™ to be accurate, and should be used as guidance only. It is the responsibility of the infusion site before each infusion to confirm that coverage for the patient has not changed.

Please see full Prescribing Information, including Boxed Warning, as well as Important Safety Information about TYSABRI on pages 66-70. - 14 -

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PRIOR AUTHORIZATIONS AND PRE-CERTIFICATIONS Depending on the type of insurance and on a patient’s specific plan or benefits, your office may need to obtain Prior Authorization, Pre-Certification, or a referral from the patient’s primary care physician before the payer agrees to cover the cost of TYSABRI® (natalizumab) and TYSABRI administration.

Prior Authorization

PreCertification

The physician is required to obtain approval from a payer before prescribing a specific medication or before performing a medical service. Without this prior approval, a payer may not provide coverage or pay for the patient’s medication or service.

Some payers require pre-approval, also known as Pre-Certification, for certain types of healthcare services, such as surgery or hospital visits. This means that your office or patient must contact the insurer to obtain approval before receiving care; otherwise, the insurer may not cover it.

Not all payers and/or services will require pre-approval, but when in doubt, it is best to contact the payer before providing any type of drug or medical service. Payers may change coverage guidelines, which could impact a patient’s ability to access therapy through their insurance. This is most common at the start of each new year. It is a best practice to check with the payer to ensure that nothing has changed. If your office does have questions about payer changes, your Biogen Infusion Reimbursement Account Manager is also available to help.

Please see full Prescribing Information, including Boxed Warning, as well as Important Safety Information about TYSABRI on pages 66-70. - 15 -

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PRIOR AUTHORIZATIONS AND PRE-CERTIFICATIONS

Healthcare Reform

Important Safety Information

FAQs and Glossary

(CONT’D)

Quick Tips for Prior Authorization and Pre-Certification Review a patient’s Summary of Benefits to understand payer-specific guidelines and requirements

Identify if a Prior Authorization for TYSABRI® (natalizumab) or a Pre-Certification for the entire service is needed

Submit Prior Authorization and other required documentation directly to the payer, as required

Ask for processing time frame, monitor progress, and confirm that authorization is approved before infusing patient

Resources to Complete Prior Authorization and Pre-Certification

Summary of Benefits

Sample Summary of Benefits

TYSABRI Benefit Investigation Worksheet

Payer-specific Prior Authorization form, found on the insurance company website

Sample Benefit Investigation Worksheet

If a payer requires a separate Letter of Medical Necessity, but does not mandate a specific format, click below for sample letters Sample Letters of Medical Necessity

Please see full Prescribing Information, including Boxed Warning, as well as Important Safety Information about TYSABRI on pages 66-70. - 16 -

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STEPS TO OBTAINING A PRIOR AUTHORIZATION Above MS™ Prior Authorization Services First, research the patient’s insurance benefits to determine if a Prior Authorization is required. (This is also available in the Summary of Benefits that can be provided by Above MS™). Be specific in what your office is requesting to be authorized. In most cases, you are asking for authorization of the infusion and TYSABRI® (natalizumab) coverage. When requesting a Prior Authorization, it is important to understand that each payer has different requirements and that your office will need to be familiar with these specific requirements. When obtaining details on the Prior Authorization process, your office will want to:

✔

Determine if the information can be phoned in, faxed, emailed, or submitted through the payer website

✔

Keep—with the authorization—a copy of everything that your office submits

✔

Find out how long it will take for a decision to be made

✔

Log any calls your office makes about the request

✔

Make sure that your office identifies the site of care for the infusion; it may make a difference

✔

Follow up with the payer if your office does not receive notification of the decision in a timely manner

Remember that your Biogen Infusion Reimbursement Account Manager is also available to assist your office with access- and reimbursement-related inquiries.

Please see full Prescribing Information, including Boxed Warning, as well as Important Safety Information about TYSABRI on pages 66-70. - 17 -

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STEPS TO OBTAINING A PRIOR AUTHORIZATION (CONT’D) Identify specific documentation that must be submitted with the request. (This is also available in the Summary of Benefits). Some types of documentation that the payer may request are:

Your office will also need to determine the Prior Authorization coverage parameters. These can include:

Letter of Medical Necessity

Number of visits or infusions

Chart notes

Time limits of authorization

Specific payer Prior Authorization form 

Diagnosis limitations

Relevant literature 

Required use of specific specialty pharmacy

MRI and other clinical data related to disease

Submission requirements

Documented failure of another product

Definition of failure on previous therapies

Steps to Obtaining a Prior Authorization

Please see full Prescribing Information, including Boxed Warning, as well as Important Safety Information about TYSABRI on pages 66-70. - 18 -

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STEPS TO OBTAINING A PRIOR AUTHORIZATION (CONT’D) Above MS™ Prior Authorization Services As a follow-up to the Benefit Investigation, the Above MS™ team provides a Prior Authorization service that can help manage the requirements of a Prior Authorization to help patients access TYSABRI® (natalizumab). Simply inform the Above MS team of how that patient will obtain TYSABRI. If a Prior Authorization is required, the service will automatically be activated for your office and your patient. Prior Authorizations often need to be renewed after a certain restriction, such as a time limit or a number of infusions, no longer applies. It’s important to keep track of these parameters and to seek renewal of a Prior Authorization in advance of when it is due. The Above MS team also provides a Prior Authorization Renewal service to help keep track of Prior Authorization expiration dates to ensure that patients don’t have an interruption in therapy because of a Prior Authorization renewal requirement.

To effectively manage Prior Authorization requests, maintain a summary sheet of each payer’s requirements for your most common payers.

Please see full Prescribing Information, including Boxed Warning, as well as Important Safety Information about TYSABRI on pages 66-70. - 19 -

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Prescribing Prescribing TYSABRI TYSABRI

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Important Safety Information

REQUESTING A MEDICAL EXCEPTION A Medical Exception is a request by your office to the payer to bypass Step Edits or other coverage restrictions so that the patient can immediately begin treatment with a nonpreferred drug. An effective Letter of Medical Necessity is tailored to your patient’s needs. Be clear about your patient’s individual circumstance—your letter should state whether you are initiating or changing treatment, or whether you want to continue your patient’s therapy but their health insurance benefits have changed. The response time from payers on Medical Exceptions is usually no more than 5 days, with some responding in less time. Some payers will do an expedited review if your office believes that the patient needs to begin treatment without delay.

Key Considerations When Writing a Letter of Medical Necessity Provide background on your patient’s condition •S  ummarize their clinical status citing diagnostic disease measures, such as magnetic resonance imaging (MRI) data and Expanded Disability Status Scale (EDSS) score

Explain why the insurer’s suggested treatment is not appropriate for your patient • L ist side effects or adverse events that the patient experienced on an insurer’s suggested treatment, if applicable

• If appropriate, list any failed medications, and provide clinical evidence of their inadequate response

•C  ite experience on similar therapies and why they are not suitable for your patient, if applicable

Explain why the treatment you recommend is the appropriate choice for your patient

• L ist any compliance concerns, if applicable

•P  rovide a clinical justification supporting the treatment you have chosen for your patient •R  eview previous treatments you have tried and what results they produced

•D  escribe individual patient considerations that impact the choice of treatment, as appropriate • If your office is associated with an MS specialist, many health plans value indicating this information in the Letter of Medical Necessity

•S  tate any patient-specific reasons for the treatment choice, such as efficacy, tolerability issues, or route of administration, if applicable •C  ite relevant literature

Please see full Prescribing Information, including Boxed Warning, as well as Important Safety Information about TYSABRI on pages 66-70. - 20 -

DECISIVE ACTION MATTERS

Prescr Prescr bb ng TYSABR TYSABR

Order ng TYSABR

C a ms n orma on or TYSABR

REQUESTING A MEDICAL EXCEPTION

Pa en Suppor

Hea hcare Re orm

mpor an Safe y nforma on

FAQs and G ossary

(CONT’D)

Additional documentation that supports your decision will strengthen your request. Be sure to include clinical and other appropriate documentation to help the health plan understand your patient’s needs. Requesting a Medical Exception

Examples of Supporting Documentation

Key Components for Consideration Coverage Approved Coverage Approved

Product Clinical Cards Immunosuppression/Infections

• The immune system effects of TYSABRI may • In Study MS1, increase certain types of infections—including the risk for infections. gastroenteritis, vaginal infections, pneumonias and treated patients tooth urinary tract infections than in placebo-treated infections, tonsillitis, and herpes infections—occurred (including serious prolonged course, patients. One cases), was observed opportunistic in a patient who more often in • In Studies MS1 TYSABRIreceived TYSABRI infection, a cryptosporidial and MS2, an PLEGRIDY ® gastroenteritis increase in infections corticosteroids. in Study MS1. with a However, the (peginterferon increase in infections was seen in patients concurrently to the increase in placebo-treated in TYSABRI-treated Demonstratedthe clinical receiving short beta-1a) • Concurrent patients who courses of patients who and MRI Efficacy on Physical had a statistically use of antineoplastic, received steroids. received steroids endpoints infections over was similar Disability the risk observed immunosuppressant, or immunomodulating at 1 year 1 Progression Clinical significant 42% AVONEX delays physical with use of TYSABRI • In Studies MS1 relative endpoints * disability reduction agents may further effect on progression and MS2, the alone. rate of any type increase the risk treated patients • 36% relative in the risk of increased 12 weeks vs of infection was of and placebo-treated placebo risk reduction physical disability Meaningful efficacy across multiple endpoints approximately • In Study MS1, patients. 1* vs 0.29) 1.5 per patient-year 37% reduction in risk of increased P=0.0007) (0.17 sustained for in annualized the † ‡ physical in bothreduction treated patients. incidence of serious infections disability 49% relative of 2relapse of patients relapsed ) at 2 with yearsAVONEX [TECFIDERA 27% (n=410) relapse TYSABRI- in risk at years vs(proportion 1 • 39% placebo83% Most patients (p=0.02) was approximately rate (ARR)† relative of TYSABRI did not interrupt vs placebo 46% (n=408); P<0.0001]1 risk reduction 3% in TYSABRI-treated (PLEGRIDY patients P=0.0003) treatment with Laboratory were free 0.26 vs patients and in the TYSABRI during § progression Test Abnormalities proportion ofplacebo placebo in placebo-in annualized relapse rate reduction at 2 •years [TECFIDERA 0.172 (n=410) vs 12-week sustained infections. 53% relative at 2 0.40; AVONEX significantly (ARR) of patients physical years vs 71% 38% • In clinical trials, reduces relapses relative 0.364 (n=408); P<0.0001]1 and with relapsesdisability of risk effective TYSABRI was forplacebo reduction patients with multiple sclerosis (MS) clinically placebois proven patients early signs observed to induce basophils, and (PLEGRIDY of in the (p<0.001) 0.11; ofP=0.0383) 1 syndrome nucleated red *Study Design: A 2-year double-blind, placebo-controlled study in 1234 patients forisolated the Determination the Efficacy and Safety of Oral Fumarate in (CIS) proportion 0.19 vs placebo blood cells. Observedincreases in circulating lymphocytes, returning to baseline of patients Relapsing-Remitting MS (DEFINE). Patients experienced Proven at least 1 relapse over the year preceding the trial or had a brain magnetic resonance imaging 0.29; changes persisted levels usually monocytes, with disability 32% reduction in (MRI) scaneosinophils, demonstrating at least 1 gadolinium-enhancing (Gd+) lesionReduction within 6 weeks randomization and had an Expanded Disability Status Scale TYSABRI induces within 16 weeks MRIofyear annualized of(ARR) during TYSABRI relapse Relapse endpoints mild decreases progression after the last among (EDSS) score ranging from 0 to 5. MRI evaluations were at baseline, month 6,rate 1, and year 2 in a patients subset of patients (44% in DEFINE). Rates exposure, completing 2* 2 performed years (p=0.002) in hemoglobin dose. Elevations but were reversible, (PLEGRIDY levels that are Relapses were defined as new or recurrent neurologic symptoms not associated•with fever or infection that lasted for at least 24 hours and were 67% 67% Adverse Reactions 0.07 vs frequently transient.of neutrophils relative relative were by new *When the analysis includes patients observed. reduction accompaniednot objective neurologic findings. riskinreduction who (PLEGRIDY did not complete • The most common 2annualized yearsofon by 18% inmany (0.22 vs placebo therelapses AVONEX Proportion of patients relapsed is the number of patients who had a relapse the course howtherapy, thosereduced ARR relapse 3.6independent 1 of a trial, (0.67 vsover mean vs 0.82, 0.67) 1 respectively; adverse reactions rateofat 2 years placebo number p=0.04).vs placebo were patients had. • 86% relative 10.9; P<0.0001) reported at an new or newly vs placebo headache (38% incidence of ≥10% 51% risk reduction inpatient-years vs 33%), fatigue (21% vs 17%), clinically definite ARR=the total number of relapses divided by reduction the number of in the study. enlarging placebo multiple with TYSABRI sclerosis arthralgia (19% (27% (CDMS) conversion in the mean T2 hyperintense 1.4; at 3 years vs placebo and ≥2% difference 67% P<0.0001) withnumber vs 14%), depression vs 21%), infusion reactions AVONEX gastroenteritis (adjusted, of TYSABRI p<0.001; 44% 1,3 with unadjusted, p=0.002) (11% vs 9%), lesions (24% || patients (19% vs 16%), and vaginitis were urinary tract infectionsefficacy on physical • The most frequently pain in extremity vs 18%),Demonstrated disability progression free of relapse of Gd-enhancing lesions patients (10% vs 6%). Subcutaneous (16% vs 14%), (p<0.001) 1 at 2 years vs (PLEGRIDY urinary tract infectionreported serious adverse (12%risk 38%rash relative reduction in disability at 2 years 16% (n=410) vs placebo 27% vs 9%), 41% of placebo dosing reactions in Study *Study[TECFIDERA 0.2 vs AVONEX (0.8% vs 0.3%) hasprogression been shown to significantly population: including anaphylaxis/anaphylactoid once every MS1 were infections and pneumonia (n=408); P=0.0050]1 of 0.0–5.0 reduceThe brain lesions study (0.6% vs 0%), (3.2% vs 2.6% included and ≥2 relapses 14 days attempt [0.6% acute reaction [0.8% placebo), including Study design: vs 0.3%]), and within the patients with2-year Established vs 0%]), depression hypersensitivity reactions relapsingstudy Approximately 5 out of 6 (84%) TECFIDERA patients experienced no disability progression over the cholelithiasis 3 years • Based on animal Reduction MS (1.1% vs 0.3%, 1512 patients The efficacy of prior to 75% reduction (1.0% vs 1.0%, (1.0% vs 0.3%). 1 in gadolinium-enhancing inrelapsing the study, who had a baseline PLEGRIDY MRI activity data, TYSABRI period (vs 73% of placebo patients) with including (Gd+) with at least new or newly lesions suicidal was assessed Expanded benefit justifies may cause fetal vs baseline at 2 years1†‡ ideation or MS. The 1 within Disability enlarging the potential harm. TYSABRI primary from the 12 months the placebo-controlled 92% Status Scale Disability progression is defined as at least a 1-point increase from baseline EDSS aofbaseline ≥1.0 (or at least a T2 1.5-point increase for patients withfrom baseline risk to the fetus. endpoint hyperintense relative should be used prior to (EDSS) score EDSS score reduction excluded EDSS of 0) sustained for 12 weeks. 91% reduction lesions, and was ARR. Secondary during pregnancy randomization. first in the of 1, or patients inplacebo T2 lesion volume time to confirmed mean only if the potential a 1.5-point endpoints year (48 weeks) with progressive number †Primary increase of of a 2-year (0.1 included vs placebo at 18 months vsendpoint. disability Gd+ lesions 1§ǁ 1.2; p<0.001) for patients (p<0.001) study, including 2 forms of MS.1,2 progression, the proportion at with

Clinical

Attributes CLINICAL ATTRIBUTES

Requesting a Medical Exception

Clinical Attributes CLINICAL ATTRIBUTES

Key Components for Consideration Coverage Approved Coverage Approved

Health Plan Determination Product not covered and Medical Exception needed

Requesting a Medical Exception Medical Exception Guide

Product Clinical Cards

Health Plan Determination Coverage Denied

Clinical

Attributes CLINICAL ATTRIBUTES

PLEGRIDY Clinical Attributes CLINICAL ATTRIBUTES

1,2

(peginterferon

Demonstratedthe clinical Efficacy on and MRI Physical

beta-1a) had a statistically endpoints Disability Progression at 1 year significant * effect on risk of increased physical disability for

Clinical 42% relative AVONEX delays physical endpoints In the DEFINE* Study: reduction disability progression in the

12 weeks

vs placebo (0.17 Meaningful efficacy across multiple endpoints vs 0.29) 37% reduction

sustained in risk of increased physical disability 49% relative reduction in risk at of 2relapse of patients relapsed ) at 2 with years [TECFIDERA 27% (n=410) years vs(proportion AVONEX placebo83% (p=0.02) of TYSABRI patients vs placebo 46% (n=408); P<0.0001] were freevsofplacebo progression 12-week sustained 53% relative reduction in annualized rate (ARR) at 2 years (n=410) at [TECFIDERA AVONEXrelapse 2 years vs0.172 significantly reduces relapses physical disability 71% placebo 0.364 (n=408); P<0.0001] and is proven effective of multiple sclerosis (MS) clinically for patients with patients early signs (p<0.001) isolated syndrome (CIS) of

· Step therapy required · A Prior Authorization was denied

Proven

Reduction 32% reduction in annualized MRI endpoints of(ARR) Relapse Rates among patients completing 2 years (p=0.0 relapse rate 02)

67% relative reduction in annualized (0.22 vs 0.67) relapse rate at 2 years vs placebo

51% reduction in clinically definite multiple sclerosis at 3 years vs placebo (CDMS) conversion with 67% (adjusted, AVONEX of TYSABRI p<0.001; 44% unadjusted,

p=0.002) patients were Demonstrated efficacy on physical disability progression free of relapse patients Subcutaneous (p<0.001)

at

2 years 38% relative risk reduction in disability 2 years [TECFIDERA 16%dosing (n=410) vs placebo 27% AVONEX hasprogression been shown at once every to significantly reduce brain (n=408); P=0.0050] lesions 14 days Established Approximately 5 out of 6 (84%) patients experienced no disability progression over the 2-year study Reduction 75%TECFIDERA reduction in gadolinium-enhancing inlesions MRI activity period (vs 73% of placebo patients) (Gd+) vs baseline at 2 years 92% relative

vs 41% of placebo

reduction

91% reduction in T2 lesion in the placebovolume vs placebo at 18 months (0.1 vs 1.2; p<0.001) mean number of Gd+ lesions (p<0.001) at 2 years vs Significant impact on MRI activity TYSABRI, please The exact relationship between see pages 1 through85% relative reduction in the Indication including Boxed 83% magneticT2-weighted number of new or newly enlarging hyperintense over 2 years resonance imaging relative (MRI) lesions 3 Warning. reduction and a patient’s clinical status [TECFIDERA 2.6 (n=152) vs placebo 17 (n=165); P<0.0001] in the meanfindings is unknown. lesions AVONEX Indication number of new at 2hypointense and Important yearsSafety (1.9lesions 72% relative reduction in the number of new T1-weighted over 2 years [TECFIDERA 1.5 or enlarging vsInformation 11.0; T2-hyperintense p<0.001) Indication (n=152) vs placebo 5.6 (n=165); P<0.0001] AVONEXin the (interferon 90% relative odds reduction number beta-1a) of Gd+ lesions at 2 years [TECFIDERA 0.1 (n=152) vs placebo 1.8 isImportant indicated for the treatment of patients (n=165); P<0.0001] multiple sclerosis to slow the accumulation Safety with relapsing forms

For additional Important Safety and enclosed Information about full Prescribing Information,

Information of physical disability

of

exacerbations. and decrease Patients frequency of clinical Percentage of patients with Gd+ lesions at 2 years—0 lesions: 93% TECFIDERA (n=152) vs 62% placebothe (n=165); with multiple sclerosis in whom efficacy whovs has been demonstrated have 1 lesion: 5% TECFIDERA 10%experienced placebo; 2 lesions: TECFIDERA TECFIDERA include patients a first <1% clinical episode vs 8% placebo; 3 to 4 lesions: 0% vs 9% placebo; 5 or more lesions: <1% TECFIDERA vs 11% placebo and have MRI features consistent with multiple

Indication

Important Safety Information  Patients and their caregivers

sclerosis.

should to their prescribing physician.

be advised report immediately Tecfidera (dimethyl fumarate) indicatedor forpsychosis the treatment of patients withto relapsing forms of multiple suicidalisideation, anysclerosis. symptoms have been

These symptoms,

of depression,

reported with increased frequency and cases of suicide, Selected Important Safety Information with patients receiving AVONEX. depression or other severe psychiatric

If a patient

develops symptoms, cessation TECFIDERA is contraindicated in patients with known hypersensitivity to dimethyl fumarate or anytherapy of the of AVONEX  Severe hepatic should be considered. injury, excipients of TECFIDERA, as TECFIDERA canincluding cause anaphylaxis angioedema. Progressive multifocal cases of and hepatic failure, has beenofreported Patients leukoencephalopathy AVONEX. (PML) occurred in ashould patient be who received TECFIDERA the setting prolongedrarely in patients taking monitored for signs ofinhepatic AVONEX caution exercised when used concomitantly for 3.5 years). TECFIDERA mayinjury causeand lymphopenia lymphopenia (lymphocyte counts is predominantly <0.5x10 /Lwith alcohol or other drugs associated with hepatic injury. and flushing. The most common adverse reactions associated with TECFIDERA are flushing and gastrointestinal events. Elevations in hepatic transaminases and mean eosinophil counts have been reported. TECFIDERA should be used during pregnancy only if clearly needed and if the potential benefit justifies the potential For Important risk to the fetus. Safety Information and enclosed about TYSABRI, full Prescribing Information, includingplease see pages 2 through 4 Boxed Warning.

You can request an external review if you disagree with the denial.

†

2

‡

2

These clinical cards will be valuable reference tools as you complete your Letter of Medical Necessity.

§

TECFIDERA may cause flushing (e.g. warmth, redness, itching, and/or burning sensation). 40% of patients taking TECFIDERA reported flushing which was mostly mild to moderate in severity. Three percent of patients discontinued TECFIDERA for flushing and <1% had serious flushing events that led to hospitalization. Taking TECFIDERA with food may reduce flushing. Alternatively, administration of non-enteric coated aspirin prior to dosing may reduce the incidence or severity of flushing.

trials, 2% of patients experienced lymphocyte counts <0.5 x 10 /L for at least six months. In these patients, the majority of lymphocyte counts remained <0.5x10 /L with continued therapy. A complete blood count including lymphocyte count should be obtained before initiating treatment, after 6 months, every 6 to 12 months thereafter and as clinically indicated. Consider treatment interruption if lymphocyte counts <0.5 x 10 /L persist for more than six months and follow lymphocyte counts until lymphopenia is resolved. Consider withholding treatment in patients with serious infections until resolved. Decisions about whether or not to restart TECFIDERA should be based on clinical circumstances.

This guide includes what you need to submit to assist in the process of accessing the correct therapy of choice for your patients.

 Rare cases of anaphylaxis have been reported. Other allergic reactions have included orolingual edema, skin rash dyspnea, and urticaria. Indication  While beta interferons do not Tecfidera (dimethyl fumarate) is indicated the treatment of patients with relapsing forms of multiple sclerosis. have any known for direct cardiac toxicity, cases of congestive cardiomyopathy, and cardiomyopathy heart failure, with congestive heart failure Important Safety Information without known have been reported in patients predisposition. Patients with pre-existing conditions TECFIDERA is contraindicated in patientsthese with known hypersensitivity to dimethyl or any of the excipients of worsening shouldfumarate of their cardiac be monitored condition during for initiationand TECFIDERA can cause anaphylaxis angioedema the first dose or at any time during treatment. and continuedafter treatment  DecreasedTECFIDERA. with AVONEX. peripheral blood counts Patients experiencing signs and of anaphylaxis and angioedema (which have included difficulty breathing, in symptoms all cell lines, including rare pancytopenia have beenurticaria, reported andfrom swelling of the throat and tongue) should discontinue TECFIDERAand and thrombocytopenia, seek immediate medical care. postmarketing experience.  Seizures have A fatal casereported of progressive multifocal leukoencephalopathy (PML) occurred in a patient who received TECFIDERA. been in patients using AVONEX, including is an opportunistic viral infection of the brain caused by theinJCpatients virus (JCV) that only occurs in patients seizure. It PML with is not notypically known prior history whether these events were who are immunocompromised, and that usually leads to death or severe disability. The symptomsof associated related the effects to AVONEX, of multiple or to aare sclerosis combination of both. with PML diverse, progress over days to weeks, and include progressive weakness on one alone, side of the body or  Autoimmune clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion disorders of multiple target organs been reported. patients anddisorder, personality changes. At the first sign or have withhold TECFIDERA autoimmune develop a newand perform an consider stopping therapy. symptom suggestive of IfPML, appropriate diagnostic evaluation.  Routine periodic blood chemistry, liver function, TECFIDERA may decreasehematology, lymphocyte counts; in clinical and trialsthyroid there was a mean decrease of ~30% in lymphocyte recommended function tests are during the first year with AVONEX. counts duringtreatment which then remained stable. Four weeks after stopping TECFIDERA, mean lymphocyte  There are no counts increased not to baseline. Six percent of TECFIDERA patients and <1% of placebo patients had lymphocyte adequate andbut well-controlled studies in pregnant women. during pregnancy counts <0.5x10 has not been studied in patients with AVONEX pre-existing low lymphocyte should only if /L. be used counts. theTECFIDERA potential benefit justifies the potential in patients to the fetus.  The most common There wasside no increased incidence of serious infections observedrisk with lymphocyte counts <0.8x10 /L or effects associated with AVONEX in controlled trials, although one patient intreatment an extension developed PML in the setting of prolonged arestudy chills, fever,<0.5x10/L flu-like symptoms myalgia, and asthenia. including uncontrolled clinical lymphopenia (lymphocyte counts predominantly <0.5x10 /L for 3.5 years). In controlled and

Understand Coverage · Encourage your patients to understand their insurance coverage and the action steps they can take if a treatment is not covered · For one-on-one phone support from Above MS™, call 1-800-456-2255 to speak with a Support Coordinator.

Important AVONEX Indication and Important Safety Information Safety Information (cont’d) Important Safety Information (cont’d)

Treatment Choice You and your patient agree on a course of treatment.

TECFIDERA may cause gastrointestinal (GI) events (e.g., nausea, vomiting, diarrhea, abdominal pain, and dyspepsia). Four percent of TECFIDERA patients and <1% placebo patients discontinued due to GI events. The incidence of serious GI events was 1%. The most common adverse reactions associated with TECFIDERA versus placebo areFor flushing additional Important (40% vs 6%) and GI events: abdominal pain (18% vs 10%), diarrhea (14% vs 11%), nausea (12% vs 9%). and Safety Information enclosed full Prescribing Information, about TYSABRI, please Elevations in hepatic transaminases have been reported. A transient increase in mean eosinophil counts was seen see pages 1, including Boxed 2, and 4, Warning. during the first two months. TECFIDERA should be used during pregnancy only if the potential benefit justifies 1. PLEGRIDY [Prescribing 2. Calabresi PA, Kieseier BC, Information].the potential risk to the fetus. Encourage patients who become pregnant while taking TECFIDERA to enroll in the Cambridge, MA:pregnancy registry by calling 1-866-810-1462 or visiting www.TECFIDERApregnancyregistry.com. Arnold DL, et beta-1a for relapsing-remitting TECFIDERA al; for the Biogen; August 2014. multiple sclerosis ADVANCE Study Investigators. Lancet Neurol . 2014;13(7):657-665. (ADVANCE): a Pegylated interferon randomised, phase 3, double-blind study.

Relapsing Multiple Sclerosis (RMS) Diagnosis

Biogen is here to assist you The Above MS™ program from Biogen is committed to helping people living with MS and provides extra support, such as: Support Coordinators who offer general MS information, one-on-one MS support over the phone, additional injection training, and financial and insurance support

Accessing Your Medication Understanding your health insurance to get the relapsing multiple sclerosis (RMS) therapy you and your doctor have chosen

Peer Community that helps you connect with others living with MS, share personal experiences, and stay positive and motivated

Financial and Insurance Support to help you find the best solutions in terms of insurance counseling, Benefit Investigation, our $0 Copay Program, and copay assistance, if eligible

Nurse Educators who provide additional support to you and your care partner with injection technique and to respond to questions related to MS and treatment. They are available by phone 24/7

Letters of Medical Necessity

Your patient’s medication and/or coverage may change. These sample templates will help as you tailor your letters.

You and your doctor have chosen a therapy that is right for you

Biogen offers eligible patients: Comprehensive financial assistance, including a Copay Program*

$0

*Depending on your income or, in some cases, if your medication is obtained from an out-of-network provider, there may be an annual cap that limits the amount of assistance that you can receive over one year. People covered by Medicare, Medicaid, the VA/DoD, or any other federal plans are not eligible to enroll.

An important part of managing your MS is understanding your coverage— Above MS can help you and your doctor navigate your health insurance coverage. Call them at 1-800-456-2255 (Mon - Fri, 8:30 am - 8:00 pm ET) References: 1. US Department of Health & Human Services Website. Appealing health plan decisions. http://www.hhs.gov/ healthcare/rights/appeal/appealing-health-plan-decisions.html. Accessed May 13, 2015. 2. National MS Society. Health insurance appeal letters: a toolkit for clinicians, 2nd edition. 2009;1-162. http://www.nationalmssociety.org/NationalMSSociety/media/ MSNationalFiles/Brochures/Paper-Health-Insurance-Appeal-Letters-Toolkit.pdf. Accessed May 13, 2015.

© 2015 Biogen.

All rights reserved.

Printed in the U.S.A.

06/15

FCH-US-0829

Not an actual patient.

Working with your doctor, you have found the RMS therapy option that is most appropriate for you—now what?

Patient Brochure

Treatment-Naïve Letter You are initiating treatment for a patient who, until now, has not received RMS therapy.

2

||

2

For additional Important Safety and enclosed full Prescribing Information about TYSABRI, Information, including please see pages

Continue Letter You want to continue treatment, but your patient’s insurance has changed.

Significant impact on MRI activity

The exact relationship between magneticT2-weighted Indication 83% or newly enlarging hyperintense lesions over 2 years resonance imaging 1 through85% relative reduction in the number of new relative

a baseline

2 years defined vs as

EDSS score

of subjects relapsing, at least 1-point of 0, sustained increase

References: 1. for 12 weeks. Boxed Warning. (MRI) findings and a patient’s 3 TYSABRI [Prescribing The trial clinical status is unknown. [TECFIDERA 2.6 (n=152) vs placebo 17 (n=165); P<0.0001]1,2 reduction in the mean O’Connor PW, Information]. lesions AVONEX Indication number of new PLEGRIDY Havrdova E, et Cambridge, MA: at 2 hypointense and Important years® Safety al. A randomized, N Engl J Med. (peginterferon (1.9lesions in the number of new T1-weighted over 2 years [TECFIDERA 1.5 or enlarging vsInformation 2006;354(9):899-910. 11.0; of multiple placebo-controlled Biogen; May 2015. 2. Polman 72% relative reduction T2-hyperintense p<0.001)2 Indication 1,3 beta-1a) trial of natalizumab sclerosis. CH, (n=152) vs placebo 5.6 (n=165); P<0.0001] is indicated Results of AFFIRM for relapsing multiple for the treatment AVONEXin® the (NAtalizumab (interferon sclerosis. 90% relative odds reduction number of Gd+ lesions at 2 yearsSafety 0.1 (n=152) vs placebo 1.8 beta-1a) multicenter, is indicated and EFFIcacy Important for [TECFIDERA of double-blind the treatment of inpatients Relapsing-Remitting parallel-group (n=165); P<0.0001]1 multiple sclerosismonotherapy with relapsing forms of patients with relapsing to slow the(300 trial that accumulation Multiple Sclerosis), randomized ofSafety physical mg by intravenous Information disability forms exacerbations. Patients and 942 (30 at decrease patients a 2-year, global, infusions). the 1,2• PLEGRIDY infusion (n=152) with multiple (infrequency Percentage of patients with Gd+ lesions 2 years—0 lesions: 93% TECFIDERA placebo (n=165); a 2:1 ratio)of [n=627])vs sclerosis is contraindicated in whom efficacy or 62% to clinical placebo receive either whovs interferon (n=315) been0% have demonstrated 1 lesion: 5% TECFIDERA 10%experienced placebo; 2 lesions: <1% TECFIDERA vs 8% placebo; 3in topatients 4has lesions: TECFIDERA TYSABRI every 4 include a beta weeks forpatients *The primary first clinical episode or peginterferon, have MRI features 1 and up to 28 months endpoint at with consistent vs 9% placebo; 5 or more lesions: <1% TECFIDERA placebo years was •vs2 11% with multiple sustained time to onset sclerosis. for 12 weeks,Severe or any other a history hepatic of hypersensitivity of sustained or ≥1.5-point increase in disability, injury, Important SafetyofInformation a relapse. increase on component have including the EDSS defined as an been reported from baselinehepatitis, to natural increase of ≥1.0 of the EDSS=0 that point on the or recombinant Indication formulation. was sustained with interferon  Patients and their caregiversreported, autoimmune EDSS from baseline for 12 weeks. EDSS ≥1.0 that Increase excluded should beand hepatitis, in some beta. Asymptomatic advised Contraindications enzymes report immediately patients and raredisability confirmation within 30was Tecfidera® (dimethyl fumarate) indicated forpsychosis the treatment of patients withto relapsing forms of multiple suicidalisideation, any sclerosis. symptoms or has recurred days cases of of depression, hepatic injury to theirand elevation prescribing • TYSABRI is of ALT severe hepatic physician. upon rechallenge These symptoms, have been reported have been and AST hepatic and cases of of withcontraindicated increased failure, transaminases above observed in patients and was frequency • TYSABRI Selected Important Safety Information withsuicide, with 5 times patients who with PLEGRIDY receiving interferon is contraindicated havethe depression <1% in PLEGRIDY-treated AVONEX. has also or have or other severe upper If a patient had psychiatric develops beta. Elevations in patients who PML. been limit patients in clinical of of cessation normal TECFIDERA is contraindicated in patients with known hypersensitivity or any the should have fumarate for symptoms, Indication studies. The hadofa AVONEX signs of to dimethyl therapy in hepatic  Severe hepatic was hypersensitivity be considered. hepatic injury. patients injury, in PLEGRIDY-treated incidence (<1% placebo), including reaction 2% excipients of TECFIDERA, as TECFIDERA can(natalizumab) cause anaphylaxis angioedema. Progressive multifocal cases of and TYSABRI® to TYSABRI. hepatic of elevations failure, has Consider been AVONEX. Patients rarely in respectively. patients discontinuation is indicated patients taking be leukoencephalopathy (PML) occurred in ashould patient who received TECFIDERA the setting ofreported prolonged monitored of multiple as monotherapy for signs ofinhepatic sclerosis. of PLEGRIDY Monitor liver function(1% placebo) AVONEX forinjury and TYSABRI caution the used treatment exercised concomitantly increases for 3.5 years).orTECFIDERA may cause lymphopenia lymphopenia (lymphocyte counts is predominantly <0.5x109/L when TYSABRI, with of patients tests and alcohol the riskdrugs physicians other with relapsing if hepatic injury of PML. associated should with When with and hepatic consider occurs. forms initiating and flushing. The most common adverse reactions associated TECFIDERA are flushing and gastrointestinal injury. this risk. whether the See Important continuing © 2015 Biogen. expected benefit treatment with Safety Information All rights reserved. events. Elevations in hepatic transaminases and mean eosinophil counts have been reported. TECFIDERA of TYSABRI is Printed in the regarding sufficient to offset the risk ofthe U.S.A. 06/15 additional should be used during pregnancy only if clearlyFor needed and if the potential benefit justifies potential PML TYS-US-0557 with TYSABRI. Important For Importantplease see reverse Safety Information risk to the fetus. For additional Important 4 SafetySafety Information side Information andTYSABRI, about and enclosed about PLEGRIDY, about AVONEX, enclosed please see reverse full Prescribing side and enclosed please full Prescribing full Prescribing see pages 2 Information, Information. through 4 including Boxed Information. For additional Important Safety Information about TECFIDERA, please see reverse side

Convert Letter You need to change your patient’s treatment to a non-preferred drug.

A successful Medical Exception request clearly communicates your treatment decision for a patient based on their individual circumstances. This guide provides information and considerations for preparing a complete Medical Exception package—from submitting the correct Letter of Medical Necessity to providing the right supporting documentation.

Coverage Denied You can request an external review if you disagree with the denial.

Warning.

and enclosed full Prescribing Information and Patient Information.

3

1 FOLD

PLG-US-0300

Printed

© 2015 Biogen. All rights reserved. Printed in the U.S.A. 06/15 in the U.S.A. 06/15 © 2015 Biogen. All rights reserved. PrintedAVX-US-0193

in the U.S.A.

06/15

TEC-US-0650

References: 1. TECFIDERA [Prescribing Information]. Cambridge, MA: Biogen; April 2015. 2. Gold R, Kappos L, Arnold DL, et al. N Engl J Med. 2012;367:1098-1107. Erratum in: N Engl J Med. 2012;367:2362. 3. Biogen, Data on file.

These clinical cards will be valuable reference tools as you complete your Letter of Medical Necessity. 3

3

§

‡

†

AVONEX Indication and Important Important Safety Information (cont’d) Safety Information Important

This guide includes what you need to submit to assist in the process of accessing the correct therapy of choice for your patients.

BIMS-000034_PLEGRIDY_ClinicalCard_PRINT_DR1_GG.indd

1

7/1/15 11:48 AM

Biogen is here to assist you The Above MS™ program from Biogen is committed to helping people living with MS and provides extra support, such as: Support Coordinators who offer general MS information, one-on-one MS support over the phone, additional injection training, and financial and insurance support

Accessing Your Medication Understanding your health insurance to get the relapsing multiple sclerosis (RMS) therapy you and your doctor have chosen

Peer Community that helps you connect with others living with MS, share personal experiences, and stay positive and motivated

Financial and Insurance Support to help you find the best solutions in terms of insurance counseling, Benefit Investigation, our $0 Copay Program, and copay assistance, if eligible

Nurse Educators who provide additional support to you and your care partner with injection technique and to respond to questions related to MS and treatment. They are available by phone 24/7

Your patient’s medication and/or coverage may change. These sample templates will help as you tailor your letters.

You and your doctor have chosen a therapy that is right for you

Biogen offers eligible patients: Comprehensive financial assistance, including a Copay Program*

$0

*Depending on your income or, in some cases, if your medication is obtained from an out-of-network provider, there may be an annual cap that limits the amount of assistance that you can receive over one year. People covered by Medicare, Medicaid, the VA/DoD, or any other federal plans are not eligible to enroll.

An important part of managing your MS is understanding your coverage— Above MS can help you and your doctor navigate your health insurance coverage. Call them at 1-800-456-2255 (Mon - Fri, 8:30 am - 8:00 pm ET) References: 1. US Department of Health & Human Services Website. Appealing health plan decisions. http://www.hhs.gov/ healthcare/rights/appeal/appealing-health-plan-decisions.html. Accessed May 13, 2015. 2. National MS Society. Health insurance appeal letters: a toolkit for clinicians, 2nd edition. 2009;1-162. http://www.nationalmssociety.org/NationalMSSociety/media/ MSNationalFiles/Brochures/Paper-Health-Insurance-Appeal-Letters-Toolkit.pdf. Accessed May 13, 2015.

© 2015 Biogen.

All rights reserved.

Printed in the U.S.A.

06/15

FCH-US-0829

Not an actual patient.

Working with your doctor, you have found the RMS therapy option that is most appropriate for you—now what?

Treatment-Naïve Letter You are initiating treatment for a patient who, until now, has no

Patient Brochure

•P  rovide documentation of clinical evidence for treatment failure such as inadequate response, adverse events, or side effects, as appropriate •O  ther relevant patient information may also be included, as appropriate

Medical Exception Guide

In the DEFINE* Study:

· Step therapy required · A Prior Authorization was denied

Health Plan Determination

ǁ

TM

Support. Elevated.

• If appropriate, general medical history listing comorbidities and any medication history, including contraindications

Product not covered and Medical Exception needed

Requesting a Medical Exception

All rights reserved.

•E  DSS scores, MRI data, and relapse history

Health Plan Determination

Safety Information • Depression, (cont’d) Contraindications suicidal  Rare cases of anaphylaxis have been reported. than in patients ideation, and suicide • TYSABRI is Other allergic reactions have receiving contraindicated suicidal orolingual included dyspnea, occur more edema, placebo. skinThe ideation rash and in patients who urticaria.frequently • TYSABRI is was Indication have or have overall incidence was similar contraindicated 8% in both in patients had PML.  and While in patients who ® thedo interferons receiving lessbeta PLEGRIDY of adverse not Tecfidera (dimethyl fumarate) is indicated for the treatment of patients with relapsing forms of multiple sclerosis. depression have had a hypersensitivity haveand than any known interferon 1% in both events related TYSABRI TOUCH toxicity, cases orcardiomyopathy, placebo direct cardiac suicidal of congestive beta groups. reaction to TYSABRI. Prescribing consider heart failure, groups. ideation.and cardiomyopathy to depression Advise with Program The incidence stopping congestive If a patient • Because of patients heart failure have been reported Important Safety Information and treatment without the risk of PML, to develops known predisposition. • Seizures with Patients TYSABRI is available immediately of serious events in patients depression the with withreport are associatedTECFIDERA pre-existing conditions isPLEGRIDY. contraindicated in patientsthese to dimethyl or any of the excipients of TOUCH® Prescribing Program. orknown only through a any worsening with should fumarate other hypersensitivity less than be monitored symptom of their cardiac severe psychiatric restricted distribution for • Patients must condition the use 1% in patients TECFIDERA. during initiationand TECFIDERA can cause anaphylaxis angioedema thesymptoms, first doseofor at any time during treatment. and be enrolled in of interferon continuedafter program under to patients Decreased treatment receiving the TOUCH Prescribing with AVONEX. associated with a REMS called beta. peripheral with a PLEGRIDY blood counts Patients experiencing signs and symptoms of anaphylaxis and angioedema (which have included difficulty breathing, TYSABRI and Thelines, Program, read in all cell incidence and placebo. complete and including • Anaphylaxis haveseizure disorder. the Medication rare pancytopenia of seizures sign the Patient-Prescriber beenurticaria, reported andfrom swelling of the throat and tongue) should discontinue TECFIDERAand and thrombocytopenia, seek immediate medical care. Guide, Exercise and other Herpes Encephalitis postmarketing in clinical caution experience. Less than Enrollment Form. understand the risks serious allergic studies was when administering and Meningitis 1% ofSeizures PLEGRIDY-treated have • TYSABRI increases reactions A fatal casereported of progressive multifocal leukoencephalopathy (PML) occurred in a patient who received TECFIDERA. been urticaria. in patients PLEGRIDY are rare using AVONEX, including Discontinue the risk of developing patients complications zoster viruses. patients is an opportunistic viral infection of the brain caused by theinJC virus (JCV) that only occurs in patients seizure.PLEGRIDY with It PML notypically is not experienced prior history encephalitis and known • Injection whether of of treatment these and events meningitis caused a serious a serious site reactions, who are if related immunocompromised, thatwere usually leads or severe disability. The symptoms associated• Serious, life-threatening, to death the effects with allergic reaction to AVONEX, of multiple allergic by herpes simplex beta. The interferon sclerosis or to a combination including reaction and sometimes of both. and varicella incidence beta. on one alone, with PML are diverse, progress over days to weeks, and include progressive weakness side of the body or sclerosis patients injection occurs. such fatal cases have as angioedema was 66% of injection site necrosis, receiving TYSABRI.  Autoimmune been reported in the disorders • The duration of limbs, disturbance of occur vision, and changes in thinking, memory, and orientation leading to confusion site reactions can of multiple or PLEGRIDYclumsiness in the postmarketing target patient out of treatment organs have been (e.g., group reported.ofIfPML, the setting in multiple patients autoimmune of 1468 and personality changes. At injection the first sign orwith symptom suggestive withhold TECFIDERA use (3% were develop of subcutaneous a newand perform an• Monitor patients receiving with TYSABRI prior to onset ranged consider patients disorder, discontinue site erythema, stopping severe) who received from a few months TYSABRI for signs and therapy. appropriate diagnostic evaluation. therapy meningitis occurs, interferon  Routine necrosis. following to several years. and symptoms PLEGRIDY 11% in the placebo pain, pruritus, or periodic TYSABRI should blood chemistry, If therapy necrosis of meningitis should be administered. edema) hematology, experienced group be discontinued, liver function, at adecrease and encephalitis. is continued, healed. (0% TECFIDERA may lymphocyte counts; in clinical trials there a meantests decrease of ~30% in lymphocyte and single injection thyroid and appropriate werewas recommended function injection If multiple If herpes encephalitis severe). during administration are treatment for siteFour with lesions occur, AVONEX. site remained One TECFIDERA, mean lymphocyte necrosis. countsavoid duringtreatment the first year which then weeksDecisions after stopping should bestable. or herpes encephalitis/meningitis • Congestive  Hepatotoxicity discontinue based on patients of PLEGRIDY are no heartThere toof placebo patients had lymphocyte adequate counts increased not to baseline. Six percent of TECFIDERA andbut the extentand <1% failure, PLEGRIDY well-controlled patients near studies cardiomyopathy,9 the affected in pregnant of the low lymphocyte counts. • Clinically significant receiving until women. during healing counts <0.5x10 has not been occurs. studied in patients with AVONEX pre-existing pregnancy liver injury, including interferon area only /L. and placebo theTECFIDERA potential until it is should be used with TYSABRI benefit justifies cardiomyopathy beta. The if and acute liver failure the potential risk to in the postmarketing fully treatment incidence the fetus. cardiac requiring transplant,  The most groups. with congestive There wasside no increased of serious infections observed in patients with lymphocyte counts <0.8x10•9/L or of liver setting. Signs common condition ofincidence effects associated Monitor cardiovascular has been reported injury, including 9 withone during initiation AVONEX heart failure markedly elevated <0.5x10 /L in patients controlledwith trials, although patient intreatment an extension developed PML in the setting of prolonged as six days after in patients treated • Interferon arestudy events flu-like chills, fever, myalgia, occursymptoms including significant was 7%9 and continuation the first dose; serum hepatic and asthenia.counts beta in signs of liver lymphopenia (lymphocyte predominantly <0.5x10 /Linfor 3.5 years). In controlled and uncontrolled clinical • TYSABRI should of pancytopeniacan cause decreased injury have also enzymes and elevated total of treatment cardiac disease 9 both PLEGRIDY be discontinued bilirubin, occurred for/Lworsening been reported and severe trials, 2%peripheral of patients experienced lymphocyte <0.5 x 10 for at least six months. In these patients, the majority of laboratory withcounts in patients with occurred for the first time PLEGRIDY. evidence). as early blood additional thrombocytopenia. of their jaundice or other in 7%For Important after multiple of patients lymphocyteSafety countsInformation remained counts <0.5x109in /LAVONEX, with continued therapy. A complete blood count including lymphocyte count should evidence of significant significant doses. all please receiving cell see reverse Decreasesabout decreases sidePLEGRIDY Hypersensitivity/Antibody and before liver injury (e.g., enclosed including full Prescribing be obtained initiating treatment, after lines, 6 months, every 6 to 12 months thereafter and as clinically indicated. in white and platelet in lymphocyte Information. rare blood cell and in 1% Formation counts (below • Hypersensitivity counts receiving persist for more than six months and follow Consider treatment interruption if lymphocyte counts <0.5 xbelow 109/Linstances counts groups. (below placebo. 100 x 10 9 reactions have Monitor Results from the Multiple 0.5 3.0treatment x 10 9/L), is resolved. Consider Sclerosis x 10 9/L in patients with serious infections (e.g., anaphylaxis) The incidence /L) Collaborative patients occurred in patients lymphocyte counts until lymphopenia withholding cell counts, were Research Group (MSCRG) neutrophil all less of the efficacyfor trial, a 2-year, pivotal, randomized,of which occurred infections, of treatment differential than with AVONEXDecisions clinically double-blind, in 301 patients • Reactions usually at an incidence receiving TYSABRI, including until resolved. about or not tocounts restart(below TECFIDERA should be based on clinical 1%whether placebo-controlled bleeding, Patients diagnosed andwith phase IIIcircumstances. white blood of 1.0 to 3.5. CDMS trial similar for at least 1 year of <1%. serious systemic with myelosuppression who had1.0 baseline in both placebo x 10 9Expanded cell counts, and symptoms include urticaria, occur within 2 hours of the reactions /L), Disability Status Scale scores • Autoimmune Compared with a 30% start of TECFIDERA may cause flushing (e.g.of warmth, redness, itching,and and/or burning sensation). 40% of patients dizziness, fever, anemia. and platelet reduction may PLEGRIDY vs baseline Monitor for placebo. require rash, rigors, pruritus,the infusion. Symptoms associated • If a hypersensitivity counts disorders complete morereported hypothyroidism, Results from taking TECFIDERA flushing which wastreatment mostly mild to moderate during nausea, flushing, of the reaction occurs, intensive Controlled with these reactions multiple High-Risk Subjects AVONEX bloodin severity. Three percent of patients who monitoring Multiple hypotension, target organs Sclerosisand and controlled Prevention can with phase III trial autoimmune Studyserious discontinued for flushing <1% had flushing events that led to hospitalization. Taking experience a hypersensitivity discontinue administration autoimmune (CHAMPS), dyspnea, and of the efficacy PLEGRIDY. a 3-year, of blood ofTECFIDERA pivotal, treatment randomized, double-blind, including with AVONEX after a first clinical of TYSABRI and chest pain. • reaction should disorders cell counts. hepatitis event and had MRI features event (N=383). idiopathic develop initiate appropriate with food maywere reduce flushing. Alternatively, administration of non-enteric coatedplaceboaspirin priorHypersensitivity to not be re-treated Patients had experienced consistent have reactions were was less TECFIDERA with MS. Results a first acute demyelinating a new autoimmune adjusted for age, been thrombocytopenia, not develop antibodies with TYSABRI. more frequent Gd+ lesions shown therapy. Patients qualifying event, baseline MRI reported onthan MRI. 1%may in both T2 lesion in patients with dosing reduce the incidence or severity of flushing. with to TYSABRI in • The most PLEGRIDY disorder, interferon hyper- andvolume, and baseline number of antibodies to • Patients who Change from baseline both MS and common consider TYSABRI in T2 lesion and beta. receive

Understand Coverage · Encourage your patients to understand their insurance coverage and the action steps they can take if a treatment is not covered · For one-on-one phone support from Above MS™, call 1-800-456-2255 to speak with a Support Coordinator.

FOLD

Treatment Choice You and your patient agree on a course of treatment.

volume:stopping CD studies placebo 28 mm (AVONEX) vs 313 compared with The incidence TYSABRI after adverse associated mm (placebo). TECFIDERA may cause gastrointestinal (GI)treatment events (e.g., nausea, vomiting, diarrhea, abdominal pain, and dyspepsia). hypersensitivity patients who an extended period PLEGRIDY. with PLEGRIDY reactions (incidence of did reactions. without treatment myalgia, References: treatment Four percent of TECFIDERA patients and <1% placebo groups. patients discontinued If patients due to GI events. The incidence of serious 1. AVONEX [Prescribing greater chills, injection Information]. may be at higher Cambridge, MA: Biogen; August 2014. than are injection Collaborative risk of 10% 2. Jacobs GI events was 1%.site The interferon most common adverse reactions associated TECFIDERA versus placebo areFor flushing siteResearch LD, Cookfairwith (MSCRG). and Intramuscular DL, Rudick pain, Group at least RA, et al; Multiple Sclerosis additional Important For additional beta-1a for disease erythema, 3. Jacobs LD, Beck RW, asthenia, progression 2% in relapsing Simon JH, injection (40% vs et6%) and GIStudy events: abdominal pain (18% vs more 10%), diarrhea vsAnn 11%), nausea (12% vs 9%).and multiple(14% al; influenza-like CHAMPS sclerosis. Safety Information Important than Neurol Group. . 1996;39(3):285-294. Intramuscular please see enclosed full sclerosis. Safety placebo) interferon illness, N Engl J Med. 2000;343(13):898-904. site pruritus, beta-1a therapy initiated Prescribing Information, about TYSABRI, please during a first demyelinating reverse pyrexia, Information andhave in multiple arthralgia. side and Elevationsabout in hepatic transaminases been reported. A transient increase in mean event eosinophil counts was seen headache, see pages 1, including Boxed enclosed 2, and 4, PLEGRIDY, References: Warning. full Prescribing during the first two months. TECFIDERA should be used during pregnancy only if the potential benefit justifies 1. PLEGRIDY [Prescribing 2. Calabresi PA, the fetus. Encourage patients who become pregnant while taking TECFIDERA to enroll in the Information].the potential risk toInformation. Kieseier BC, Arnold Cambridge, MA:pregnancy registry by calling 1-866-810-1462 or visiting www.TECFIDERApregnancyregistry.com. beta-1a for relapsing-remitting DL, et al; for the Biogen; August ADVANCETECFIDERA 2014. Study Investigators. multiple sclerosis Lancet Neurol Pegylated . 2014;13(7):657-665. (ADVANCE): For additional Important Safety Information about TECFIDERA, please see reverse side interferon a randomised, and enclosedphase full Prescribing 3, double-blindInformation and Patient Information. study.

Relapsing Multiple Sclerosis (RMS) Diagnosis

© 2015 Biogen .

Details from the patient’s medical record

Convert Letter You need to change your patient’s treatment to a non-preferred drug.

A successful Medical Exception request clearly communicates your treatment decision for a patient based on their individual circumstances. This guide provides information and considerations for preparing a complete Medical Exception package—from submitting the correct Letter of Medical Necessity to providing the right supporting documentation.

Other documentation • L etters from consultants or other medical professionals that support your treatment choice •C  linical information regarding your treatment choice, such as the product’s US Prescribing Information Medical Exceptions Guide TYSABRI® (natalizumab) Clinical Attributes Not all payers and/or services will require a Letter of Medical Necessity, but when in doubt, it is best to contact the payer before providing any type of drug or medical service. Payers may change coverage guidelines, which could impact a patient’s ability to access therapy through their insurance. This is most common at the start of each new year. It is a best practice to check with the payer to ensure that nothing has changed. If your office does have questions about payer changes or about the Medical Exceptions process, your Biogen Infusion Reimbursement Account Manager is also available to help.

Please see full Prescribing Information, including Boxed Warning, as well as Important Safety Information about TYSABRI on pages 66-70. - 21 -

DECISIVE ACTION MATTERS

Prescribing Prescribing TYSABRI TYSABRI

Ordering TYSABRI

Claims Information for TYSABRI

REQUESTING A MEDICAL EXCEPTION

Patient Support

Healthcare Reform

FAQs and Glossary

Important Safety Information

(CONT’D)

There are various scenarios in which a patient may need your office to prepare and submit a Letter of Medical Necessity to obtain coverage for TYSABRI® (natalizumab). The types of letters your office may need are: •S  tep Requirement Not Met for a Treatment-Naïve Patient: Although the patient has not met the step-therapy requirement, the healthcare provider wants to start the patient on TYSABRI based on their clinical presentation •S  tep Requirement Not Met for a Patient Converting Treatment: The patient is not having an adequate response to their current therapy, but has not fulfilled the TYSABRI step-therapy requirement; however, the healthcare provider believes that TYSABRI is the appropriate clinical option for that patient •S  tep Requirement Not Met for a Patient Change of Coverage: The patient is currently being treated with TYSABRI but either the patient switches health plans or their current health plan undergoes a policy change that requires the patient to go on another therapy to fulfill the step requirement; however, the physician believes that TYSABRI continues to be an appropriate choice and does not want the patient to change therapies To download Letters of Medical Necessity templates for treatment-naïve patients, patients wishing to convert therapy, and patients wishing to remain on their current therapy who have experienced a coverage change, click below. Patient to convert to another therapy

Treatment-naïve Patient

RE: [Patient Name], [Patient Insurance ID Number] [Patient Date of Birth] Dear [Health Plan Contact Name]: This letter is regarding your coverage policy of [Enter Product Name] for my patient. I have reviewed your prescription drug policy; however, I feel that the most appropriate treatment for my patient falls outside the established policy. The most appropriate medication for initiating therapy for [his/her] relapsing multiple sclerosis (RMS) is [Enter Product Name]. I have evaluated my patient’s clinical symptoms and have provided a summary below:   

[MRI data] [Physical Disability] [Relapse]

I am prescribing [Enter Product Name] for my patient because I have concluded that it is the most appropriate therapeutic option, for the following reason(s):    

[Reason(s) this treatment is most appropriate for patient] [Choose an item.] [Further explanation for treatment choice] [Choose an item.] [Further explanation for treatment choice] [Choose an item.] [Further explanation for treatment choice]

[If a step therapy before [Product Name] is required, include reason(s) why the step therapy would not be appropriate treatment for this patient.] Also, I ask that you review any clinical information I have submitted regarding my patient when considering my request. Below, I have indicated the additional information that I have submitted with this letter: ☐ Relevant medication history ☐ Anti-JCV antibody status ☐ MRI data ☐ Patient’s history of relapses ☐ DSS history [Provide reason that [Product Name] is the most appropriate treatment for this patient based on medical history, positive or negative anti-JCV antibody status, MRI data, history of relapses, or EDSS history.] Please feel free to contact me if you require further information regarding this request, and I look forward to your response as soon as possible. Sincerely,

Letter of Medical Necessity Treatment-Naïve Patient

Letter of Medical Necessity

[Insert Date] RE: [Patient Name], [Patient Insurance ID Number] [Patient Date of Birth]

[Insert Date]

Dear [Health Plan Contact Name]:

RE: [Patient Name], [Patient Insurance ID Number] [Patient Date of Birth]

This letter is regarding your coverage policy of [Enter Product Name] for my patient. I have reviewed your prescription drug policy; however, I feel that the most appropriate treatment for my patient falls outside the established policy. The appropriate therapy at this juncture is to discontinue [Enter Product Name] and to prescribe [Enter Product Name] to treat my patient’s relapsing multiple sclerosis (RMS). I have been working with my patient since [Insert Date] to manage their disease. They have been on [Enter Product Name] since [Insert Date]. My main concerns regarding my patient’s current medication include  [Reason(s) previous treatment(s) unsuitable]  [Choose an item.]  [Choose an item.] Therefore, I am prescribing [Enter Product Name] for my patient because I have concluded that it is the most appropriate therapeutic option for the following reason(s):    

Dear [Health Plan Contact Name]: This letter is regarding your coverage policy that requires me to take my patient off of [Enter Product Name]. I have reviewed your prescription drug policy; however, I feel that the most appropriate therapy at this time is to continue on [Enter Product Name] for my patient’s relapsing multiple sclerosis (RMS). I have been working with my patient since [Insert Date] to manage their disease. My patient has been on [Enter Product Name] since [Insert Date], and during this time my patient has been stable on therapy, as summarized below:  

[No new lesions as evidenced by MRI data] since [Insert Date] [No decline in disability status] as of [Insert Date]

In my medical opinion, I believe that converting therapy is not the right choice based on my clinical judgment for the following reason(s): [Insert reason(s)].

[Reason(s) this treatment is most appropriate for patient] [Choose an item.] [Further explanation for treatment choice] [Choose an item.] [Further explanation for treatment choice] [Choose an item.] [Further explanation for treatment choice]

I have included additional documentation regarding my patient, which supports my decision. I ask that you review the information I have indicated below when considering my request:

[If a step therapy before [Product Name] is required, include reason(s) why the step therapy would not be appropriate treatment for this patient.] Additionally, I ask that you review the clinical information I have submitted, which supports my decision to change medication. Below, I have indicated the additional information that I have submitted with this letter: ☐ Relevant medication history ☐ Anti-JCV antibody status ☐ MRI data ☐ Patient’s history of relapses ☐ EDSS history

☐ ☐ ☐ ☐ ☐

Relevant medication history Anti-JCV antibody status MRI data Patient’s history of relapses EDSS history

[Provide the reason that [Product Name] is the most appropriate treatment for this patient based on medical history, positive or negative anti-JCV antibody status, MRI data, history of relapses, or EDSS history.]

[Provide reason that [Product Name] is the most appropriate treatment for this patient based on medical history, positive or negative anti-JCV antibody status, MRI data, history of relapses, or EDSS history.]

Please feel free to contact me if you require further information regarding this request, and I look forward to your response as soon as possible.

Please feel free to contact me if you require further information regarding this request and I look forward to your response as soon as possible.

Sincerely, [Name]

Sincerely, [Name]

[Name]

Patient to remain on current therapy

Letter of Medical Necessity

Letter of Medical Necessity [Insert Date]

Letter of Medical Necessity Patient Converting Treatment

Please see full Prescribing Information, including Boxed Warning, as well as Important Safety Information about TYSABRI on pages 66-70. - 22 -

Letter of Medical Necessity Patient Change of Coverage

DECISIVE ACTION MATTERS

Prescribing TYSABRI

Ordering Ordering TYSABRI TYSABRI

Claims Information for TYSABRI

Patient Support

Healthcare Reform

FAQs and Glossary

Important Safety Information

ORDERING TYSABRI (natalizumab) Acquisition Options Ordering Requirements by Type of Coverage Specialty Pharmacy Network for TYSABRI®

Please see full Prescribing Information, including Boxed Warning, as well as Important Safety Information about TYSABRI on pages 66-70.

DECISIVE ACTION MATTERS

Ordering Ordering TYSABRI TYSABRI

Prescribing TYSABRI

Claims Information for TYSABRI

Patient Support

Healthcare Reform

FAQs and Glossary

Important Safety Information

THREE ACQUISITION OPTIONS FOR ORDERING TYSABRI (natalizumab) Biogen™ has provided several options for acquiring TYSABRI®. These options are designed to provide flexibility based on the services your office provides and on your patients’ needs. Some payers may require a specific acquisition method. When researching the patient’s insurance benefits, look into all of the options that are available, to identify the one that is best for your office and your patient.

Option

Option

Option

1

2

3

Purchase from your current wholesaler

Purchase direct

Purchase TYSABRI through a Specialty Pharmacy that is authorized to distribute TYSABRI and is covered by the patient’s insurance company Note: If a Benefit Investigation is requested, your office will be informed of the particular specialty pharmacy that is required by the payer. Above MS™ support coordinators can also help identify this information through the TOUCH®Prescribing Program and get the TYSABRI prescription to the right specialty pharmacy.

If your office has questions when choosing an option regarding the services you provide, please contact your Biogen Infusion Reimbursement Account Manager. Only those orders from infusion sites and central pharmacies that are enrolled in, and are authorized by, the TOUCH Prescribing Program will be processed. If your office is using a specialty pharmacy, the order must be placed through the TOUCH Prescribing Program. The way in which TYSABRI is obtained may influence the financial responsibility of the patient. Your office may want to discuss these options with the patient before determining how TYSABRI will be ordered.

Please see full Prescribing Information, including Boxed Warning, as well as Important Safety Information about TYSABRI on pages 66-70. - 24 -

DECISIVE ACTION MATTERS

Prescribing TYSABRI

Ordering Ordering TYSABRI TYSABRI

Claims Information for TYSABRI

Patient Support

Healthcare Reform

FAQs and Glossary

Important Safety Information

ORDERING REQUIREMENTS BY TYPE OF COVERAGE Ordering requirements may differ based on the patient’s payer coverage. These options can be researched during the Benefit Investigation. Private Payers

Medicaid

Medicare

Many private payers (including some Medicare Advantage and Managed Medicaid plans) use a specialty pharmacy to purchase TYSABRI®(natalizumab). It is important to determine procurement options before treatment with TYSABRI.

Some Medicaid plans use a specialty pharmacy; some require buy-and-bill.

Traditional Medicare is currently buy-and-bill only.

The way in which TYSABRI is purchased may influence the financial responsibility for the patient. Your office may want to discuss these options and requirements with the patient before determining how TYSABRI will be ordered.

Please see full Prescribing Information, including Boxed Warning, as well as Important Safety Information about TYSABRI on pages 66-70. - 25 -

DECISIVE ACTION MATTERS

Prescribing TYSABRI

Ordering Ordering TYSABRI TYSABRI

Claims Information for TYSABRI

Patient Support

Healthcare Reform

FAQs and Glossary

Important Safety Information

SPECIALTY PHARMACY NETWORK FOR TYSABRI (natalizumab) If you need to check on the status of your TYSABRI® shipments or to follow up on TYSABRI reorders, you can either call the specialty pharmacy directly or check the status on www.TOUCHprogram.com. The following specialty pharmacy providers have been authorized by Biogen™ to supply TYSABRI under the restricted distribution requirements of the TOUCH® Prescribing Program. When calling a specialty pharmacy, ask to speak with a member of the TYSABRI team.

Specialty Pharmacy Name

Phone

Fax

AcariaHealth

1-877-928-5120

1-877-928-5121

Accredo

1-866-898-0034

1-877-201-4499

Aetna Specialty Pharmacy

1-866-782-2779

1-860-907-3862

BioScrip Specialty Pharmacy

1-877-517-9299

1-952-516-8805

CarePlus Pharmacy (a CVS Caremark company)

1-800-498-5601

1-888-615-4490

Cigna Specialty Pharmacy Services

1-800-351-3606

1-800-351-3616

CVS Caremark Specialty Pharmacy

1-800-237-2767

1-800-323-2445

OptumRX

1-866-440-0941

1-800-853-3844

Walgreens Specialty Pharmacy

1-888-884-8714

1-877-231-8302

Please see full Prescribing Information, including Boxed Warning, as well as Important Safety Information about TYSABRI on pages 66-70. - 26 -

DECISIVE ACTION MATTERS

Prescribing TYSABRI

Ordering TYSABRI

Claims Claims Information Information for TYSABRI for TYSABRI

Patient Support

Healthcare Reform

FAQs and Glossary

Important Safety Information

CLAIMS INFORMATION FOR TYSABRI (natalizumab) Claims Information for TYSABRI® Physician Office Billing Hospital Outpatient Billing Payer Coverage and Payment for Drugs and Services Appealing Denied Claims

Please see full Prescribing Information, including Boxed Warning, as well as Important Safety Information about TYSABRI on pages 66-70.

DECISIVE ACTION MATTERS

Prescribing TYSABRI

Ordering TYSABRI

Claims Claims Information Information for TYSABRI for TYSABRI

Patient Support

Healthcare Reform

Important Safety Information

FAQs and Glossary

CLAIMS INFORMATION FOR TYSABRI (natalizumab) (CONT’D) Once your patient has received each TYSABRI® infusion, your office may submit a claim to the patient’s insurance plan. Depending on the patient’s benefits, your office may submit a claim for the drug, for the administration services, or for both. The information within this section reviews some of the codes commonly associated with the administration of TYSABRI. However, your office should check directly with the patient’s insurance plan to verify coding recommendations.

Quick Tips for Coding • ICD-10-CM (International Classification of Diseases, Tenth Revision, Clinical Modification) Diagnosis Code: G35 (Multiple Sclerosis)1 –A  s of October 1, 2015, Centers for Medicare & Medicaid Services (CMS) requires the use of the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) as the medical code set for medical diagnoses and inpatient hospital procedures.2,3 The transition to ICD-10-CM is also required for all individuals covered by the Health Insurance Portability and Accountability Act (HIPAA).4 These codes replace the ICD-9-CM codes that were previously used •H  CPCS (Healthcare Common Procedure Coding System): J2323 (Injection, natalizumab, 1 mg)5 •D  rug Units: 300 (Dose of TYSABRI is 300 mg) •N  ational Drug Code: 64406-008-01 (10-digit format)6 •C  PT (Current Procedural Terminology) Administration Code: 96413 (Chemotherapy administration, intravenous infusion technique up to 1 hour, single or initial substance/drug). Some payers may require the use of CPT code 96365 (Intravenous infusion, for therapy, prophylaxis, or diagnosis [specify substance or drug]; initial, up to 1 hour)7 The National Drug Code (NDC) for TYSABRI is 64406-008-01.6 Although FDA uses a 10-digit format when registering NDCs, payers often require an 11-digit NDC format on claim forms for billing purposes. It is important to confirm with your payer which NDC format they require. Guidelines for reporting the NDC in the appropriate format, quantity, and unit of measure vary by state and by payer and should be reviewed prior to submitting a claim. Providers accessing TYSABRI through the specialty pharmacy will not need to submit a claim for reimbursement for TYSABRI, because it is being ordered by the specialty pharmacy, but will have to submit a claim for reimbursement for administration services associated with TYSABRI. Patients are invoiced directly for any applicable copayments or coinsurances that they are responsible for.

Please see full Prescribing Information, including Boxed Warning, as well as Important Safety Information about TYSABRI on pages 66-70. - 28 -

DECISIVE ACTION MATTERS

Prescribing TYSABRI

Ordering TYSABRI

Claims Claims Information Information for TYSABRI for TYSABRI

Patient Support

Healthcare Reform

FAQs and Glossary

Important Safety Information

PHYSICIAN OFFICE BILLING Physician offices that administer TYSABRI® (natalizumab) to patients submit claims on the CMS-1500 claim form or its electronic equivalent. The following codes may be appropriate for TYSABRI and related services when provided in a physician office.

Diagnosis Code

Location on CMS-1500 Payer Form (Electronic Equivalent)1

Code and Description

Active Code as of October 1, 2015

ICD-10-CM1

G35 (Multiple Sclerosis)

Inactive Code as of October 1, 2015

Field 21 (Loop: 2300; Segment: HI01-2)

340 (Multiple Sclerosis)

ICD-9-CM8

It is important to know that as of October 1, 2015, CMS will NOT accept ICD-9-CM codes on any claims submissions (electronic or paper) that have a date of service or a date of discharge on or after October 1, 2015. Failure to use ICD-10-CM codes will result in the return or rejection of reimbursement claims.9 HCPCS Code5

Description

Location on CMS-1500 Form

Units

Location on CMS-1500 Form

J2323

Injection, natalizumab, 1 mg

Field 24D

300

Field 24G

When filling in the HCPCS Code, remember that, because J2323 is per 1 mg, it does not represent the entire vial of drug. To report the use of an entire vial of TYSABRI, you must report 300 units in Field 24G.5

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CPT Code7

Description

Location on CMS-1500 Form

Units

Location on CMS-1500 Form

96413*

Chemotherapy administration intravenous infusion technique; up to 1 hour, single or initial substance/drug

Field 24D

1

Field 24G

Typically, administration of TYSABRI® (natalizumab) requires approximately 1 hour of infusion. The total number of hours (from when the medication starts dripping until it stops) is reported in the “Days or Units” column (Field 24G) of the CMS-1500 claim form. One (1) unit of code 96413 may be used to report the time from the start of the infusion until 60 minutes into the infusion. In instances where the infusion requires from 61 to 150 minutes, 1 unit of 96415 (chemotherapy administration, intravenous infusion technique; each additional hour, 1 to 8 hours) may also be billed.7 *Some payers may require the use of CPT code 96365 (intravenous infusion, for therapy, prophylaxis, or diagnosis [specify substance or drug]; initial, up to 1 hour). If the payer requires CPT code 96365 for the initial hour of the infusion, use CPT code 96366 (intravenous infusion, for therapy, prophylaxis, or diagnosis [specify substance or drug]; each additional hour) to report each additional hour.7

Please see full Prescribing Information, including Boxed Warning, as well as Important Safety Information about TYSABRI on pages 66-70. - 30 -

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Physician Office Coding Summary for Electronic Claim Submission for TYSABRI (natalizumab) The table below provides examples of relevant codes when billing for TYSABRI® when administered in the physician office setting, and where these codes are reported within your electronic claims software. Requirements and location of information will vary by payer.

EXAMPLES OF RELEVANT CODES FOR TYSABRI AND ELECTRONIC BILLING LOCATIONS; PHYSICIAN OFFICE10 Information

Code

CMS-1500 Location

Electronic Loop

Equivalent Segment

HCPCS Code5

J2323

Field 24D

2400

SV101

HCPCS Units

300

Field 24G

2400

SV104

CPT Code7

96413

Field 24D

2400

SV101

CPT Code Units

1

Field 24G

2400

SV104

ICD-10-CM Code1 (primary)

G35 (multiple sclerosis)

Field 21

2300

HI01-2 through HI12-2

National Provider Identification (NPI) Number

Provider specific

Field 17B

2310A

NM109

Prior Authorization Number

Payer specific

Field 23

2300

REF02

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SAMPLE CMS-1500 CLAIM FORM Sample CMS-1500 Claim Form: Private Payer and Medicare

Field 17B: Indicate the National Provider Identification (NPI) number here. Field 21: Indicate the most medically appropriate diagnosis code. ICD-10-CM code G35 may be appropriate to report MS.

Field 23: If required, report Prior Authorization number here.

Field 24D: For TYSABRI® (natalizumab), use the HCPCS code required by the payer. Also include appropriate codes to report drug administration procedures. NOTE: For TYSABRI obtained through a specialty pharmacy, report the drug administration codes here. Check with the payer to identify how to report the drug that was infused if needed.

Field 24G: Indicate the appropriate HCPCS and/or CPT code units.

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HOSPITAL OUTPATIENT BILLING Hospital outpatient departments (eg, hospital-based infusion sites) that administer TYSABRI®(natalizumab) to patients submit claims on the CMS-1450/UB-04 claim form or its electronic equivalent. The following codes may be appropriate for TYSABRI and related services when provided in a hospital outpatient department.

Diagnosis Code

Location on CMS-1450/UB40 Form (Electronic Equivalent)1

Code and Description

Active Code as of October 1, 2015

ICD-10-CM1

G35 (Multiple Sclerosis)

Field 67

Inactive Code as of October 1, 2015

340 (Multiple Sclerosis)

ICD-9-CM8

It is important to know that as of October 1, 2015, CMS will NOT accept ICD-9-CM codes on any claims submissions (electronic or paper) that have a date of service or a date of discharge on or after October 1, 2015. Failure to use ICD-10-CM codes will result in the return or rejection of reimbursement claims.9 HCPCS Code5

Description

Location on CMS-1450/UB-04 Form

Units

Location on CMS-1450/UB-04 Form

J2323

Injection, natalizumab, 1 mg

Field 44

300

Field 46

Because J2323 is per 1 mg, it does not represent the entire vial of drug. To report the use of an entire vial of TYSABRI, you must report 300 units in Field 46.5 Some payers prefer that the units of service in Field 46 be equal to the number of vials used. We recommend verifying which method of reporting units of service each payer prefers. Please see full Prescribing Information, including Boxed Warning, as well as Important Safety Information about TYSABRI on pages 66-70. - 33 -

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Revenue codes are required for hospital outpatient billing and will vary depending on the revenue center to which your hospital maps TYSABRI® (natalizumab). Typically, TYSABRI will be reported using revenue codes such as:

Revenue Code11

Description

0250

Drugs and Biologics

0636*

Hemophilia blood clotting factors

0510

Clinic visit

0260

IV infusion

Location on CMS-1450/UB-04 Form

Field 42†

*For Medicare, revenue code 0636 must be used in conjunction with HCPCS code 96413. Private payers may also require revenue code 0636 for TYSABRI. † The appropriate revenue code should be entered into Field 42 of the CMS-1450/UB-04 claim form.

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CPT Code7

Description

Location on CMS-1450/UB-04 Form

Units

Location on CMS-1450/UB-04 Form

96413*

Chemotherapy administration intravenous infusion technique; up to 1 hour, single or initial substance/drug

Field 44

1

Field 46

Typically, administration of TYSABRI® (natalizumab) requires approximately 1 hour of infusion. The total number of hours (from when the medication starts dripping until it stops) is reported in the “Days or Units” column (Field 46) of the CMS-1450/UB-04 claim form. One (1) unit of code 96413 may be used to report the time from the start of the infusion until 60 minutes into the infusion. In instances where the infusion requires from 61 to 150 minutes, 1 unit of 96415 (chemotherapy administration, intravenous infusion technique; each additional hour, 1 to 8 hours) may also be billed.7 *Some payers may require the use of CPT code 96365 (intravenous infusion, for therapy, prophylaxis, or diagnosis [specify substance or drug]; initial, up to 1 hour). If the payer requires CPT code 96365 for the initial hour of the infusion, use CPT code 96366 (intravenous infusion, for therapy, prophylaxis, or diagnosis [specify substance or drug]; each additional hour) to report each additional hour.7

Please see full Prescribing Information, including Boxed Warning, as well as Important Safety Information about TYSABRI on pages 66-70. - 35 -

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(CONT’D)

Hospital Outpatient Department Coding Summary for Electronic Claim Submission for TYSABRI (natalizumab) The table below provides examples of relevant codes when billing for TYSABRI® when administered in the hospital outpatient setting and where these codes are reported within your electronic claims software. Requirements and location of information will vary by payer. EXAMPLES OF RELEVANT CODES FOR TYSABRI AND ELECTRONIC BILLING LOCATIONS; HOSPITAL OUTPATIENT12 Information

Code

CMS-1450/UB-04 Location

Electronic Loop

Equivalent Segment

HCPCS Code5

J2323

Field 44

2400

SV202-2

HCPCS Units

300

Field 46

2400

SV205

CPT Code7

96413

Field 44

2400

SV202-2

CPT Code Units

1

Field 46

2400

SV205

ICD-10-CM Code1 (primary)

G35 (multiple sclerosis)

Field 67

2300

HI01-2

National Provider Identification (NPI) Number

Provider specific

Field 56

2010AA

NM1/85/09

Revenue Code11

0250 0636 0510 0260

Field 42

2400

SV201

Please see full Prescribing Information, including Boxed Warning, as well as Important Safety Information about TYSABRI on pages 66-70. - 36 -

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SAMPLE CMS-1450/UB-04 CLAIM FORM __

__

__ 4

3a PAT. CNTL # b. MED. REC. #

2

__

1

6

5 FED. TAX NO.

8 PATIENT NAME

9 PATIENT ADDRESS

a

11 SEX

31 OCCURRENCE CODE DATE

12

DATE

c

ADMISSION 13 HR 14 TYPE 15 SRC 16 DHR 17 STAT

32 OCCURRENCE DATE CODE

18

19

20

34 OCCURRENCE CODE DATE

33 OCCURRENCE DATE CODE

Sample CMS-1450/UB-04 Claim Form: Private Payer and Medicare

a

b

b

10 BIRTHDATE

TYPE OF BILL

7

STATEMENT COVERS PERIOD FROM THROUGH

CONDITION CODES 24 22 23

21

35 CODE

38

25

26

39 CODE

40 CODE

VALUE CODES AMOUNT

27

36 CODE

OCCURRENCE SPAN FROM THROUGH

d 28

e

29 ACDT 30 STATE

37

OCCURRENCE SPAN FROM THROUGH

41 CODE

VALUE CODES AMOUNT

VALUE CODES AMOUNT

a b c d 42 REV. CD.

44 HCPCS / RATE / HIPPS CODE

43 DESCRIPTION

45 SERV. DATE

46 SERV. UNITS

47 TOTAL CHARGES

48 NON-COVERED CHARGES

49

1

1

2

2

3

3

4

4

Field 42: Include appropriate revenue codes.

Field 44: Use appropriate HCPCS/ CPT codes to report TYSABRI®(natalizumab) and infusion.

5

6

7

8

9

10

11

12

13

14

Field 46: Indicate the appropriate HCPCS and/or CPT code units. 5

6

7

8

9

10

11

12

13

14

15

15

16

16

17

17

18

18

19

19

20

20

21

Field 67: Indicate the most PAGE OF medically appropriate diagnosis code. In this example, ICD-10-CM G35 is used to report MS.

21

22

23

50 PAYER NAME

22

TOTALS

CREATION DATE 52 REL. INFO

51 HEALTH PLAN ID

53 ASG. BEN.

23

55 EST. AMOUNT DUE

54 PRIOR PAYMENTS

A

56 NPI 57

A

B

OTHER

B

C

PRV ID

58 INSURED’S NAME

62 INSURANCE GROUP NO.

A

B

B

C

C

65 EMPLOYER NAME

64 DOCUMENT CONTROL NUMBER

63 TREATMENT AUTHORIZATION CODES

C

Field 56: Indicate the National Provider Identification (NPI) number here.

61 GROUP NAME

59 P. REL 60 INSURED’S UNIQUE ID

A

A

A

B

B

C

C

66 DX

67 I

A J

69 ADMIT 70 PATIENT DX REASON DX PRINCIPAL PROCEDURE a. 74 CODE DATE

B K a

b

C L

OTHER PROCEDURE CODE DATE

b.

OTHER PROCEDURE CODE DATE

e.

c

D M

71 PPS CODE OTHER PROCEDURE CODE DATE

E N 75

72 ECI

F O 76 ATTENDING

G P NPI

LAST c.

OTHER PROCEDURE CODE DATE

d.

OTHER PROCEDURE CODE DATE

77 OPERATING

LAST

c

79 OTHER

d UB-04 CMS-1450

APPROVED OMB NO.

78 OTHER

b

LAST

68

73

QUAL FIRST

NPI

LAST 81CC a

80 REMARKS

H Q

QUAL FIRST

NPI

QUAL FIRST

NPI

QUAL FIRST

THE CERTIFICATIONS ON THE REVERSE APPLY TO THIS BILL AND ARE MADE A PART HEREOF.

NUBC

™

National Uniform Billing Committee

LIC9213257

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PAYER COVERAGE AND PAYMENT FOR DRUGS AND SERVICES Medicare, private payers, and Medicaid have different reimbursement policies. Being familiar with these differences will enable your office to avoid potential challenges with payers.

Medicare (and Sequestration) Medicare reimburses physician services, including drug administration services, based on the Medicare Physician Fee Schedule (MPFS) at the Average Sales Price (ASP) plus 6%, as published quarterly by the Centers for Medicare & Medicaid Services (CMS).13 Medicare pays 80% of the allowed charges for TYSABRI® (natalizumab) and its administration, with the beneficiary (or supplemental insurance) responsible for the remaining 20% coinsurance.14 Medicare Part B Drug Average Sales Price (ASP) This link will take you to a website that is outside the control of Biogen™. We provide links as a public service and for informational purposes only.

Allowed Amount Fee Schedule or ASP + 6%

CPT or HCPCS

$

Effective Monday, April 1, 2013 a 2% across-the-board cut in Medicare provider payments took effect. The sequestration is required by the Budget Control Act that was signed into law in August 2011. All Medicare physician claims with a date of service on or after April 1, 2013, will be subject to a 2% payment cut.15

$

Costs for physician-administered drugs

included on the physician claim will also be subject to the 2% cut. The cut will be applied to the payment itself, not the underlying “allowed charge” in the Medicare fee schedule. As a result, beneficiary copayments and deductibles will not change. In other words, the 2% cut is imposed only on the 80% of the full allowed charge amount that a participating physician would receive directly from Medicare.16

Please see full Prescribing Information, including Boxed Warning, as well as Important Safety Information about TYSABRI on pages 66-70. - 38 -

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PAYER COVERAGE AND PAYMENT FOR DRUGS AND SERVICES (CONT’D) Medicaid and Private Payers Some payers may require prior authorization for TYSABRI® (natalizumab), or they may have other requirements. Medicaid reimbursement for TYSABRI and its administration service varies by state. For private payers, reimbursement for TYSABRI and its administration services will vary, depending on the specific provisions outlined in your contract with the payer.

CPT

Amount Determined by the State or Payer

or

Medicaid rates are updated quarterly and can be found at the link below:

HCPCS

Cost Share Varies by State or Payer

State Medicaid & Children’s Health Insurance Program (CHIP) Policies This link will take you to a website that is outside the control of Biogen™. We provide links as a public service and for informational purposes only.

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APPEALING DENIED CLAIMS If a claim for TYSABRI® (natalizumab) is denied or is improperly reimbursed, your office may consider submitting an appeal. The appeals process varies by payer, but your office may find the following steps beneficial in your approach. Above MS™ support coordinators are available to assist you during the appeals process. Resources that may be helpful as your office goes through the process are: • TYSABRI Benefit Investigation Worksheet • Summary of Benefits • The insurance company website for processes and/or forms • A sample Letter of Appeal, if the payer does not have a specific appeals format (sample Letter of Appeal can be found on following page)

1 Understand the Denial Reason Review the Explanation of Benefits for the denial reason(s). See Physician Office Billing and Hospital Outpatient Billing for appropriate codes. The most common reasons for denials include:

•U  se of incorrect CPT/HCPCS code(s) • Incorrect number of units billed • T ransposed, missing, or truncated policy numbers •N  o Prior Authorization on file •M  issing Prior Authorization number on claim •P  atient’s insurance mandates the use of a specialty pharmacy

2 Appeal the Claim Contact the payer to obtain their appeals process. Elements to consider in your inquiry include:

•Y  our ability to submit the appeal via fax or electronically (online)

•A  ddress and phone number for their appeals department

3 Monitor the Claim Check with the payer to confirm that they have received your request and to check the status of its decision. Notify the patient of instances where your office may need his or her involvement. Often, the patient, too, can submit an appeal to the payer.

•P  ayer-specific timeline and process for responding to appeal requests

•P  ayer-specific appeals form that must be completed •N  ame and phone number of your provider representative

•N  ame and address of their medical director

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(CONT’D) If a payer does not have a specific appeals format, click below

[PHYSICIAN PRACTICE LETTERHEAD]

Date: To: [Name of Insurance Company] [Address] [City], [State] [ZIP Code] Re: [Patient name]

Sample Letter of Appeal Guide to Appealing Denied Claims

Diagnosis: [Patient’s diagnosis and ICD-10-CM Code] Policy Number: Group Number: Subscriber Name: To Whom It May Concern: I am writing on behalf of my patient [insert name], policy number [insert number], to request reconsideration of a claim. [Insert drug name] was administered to [insert patient name] on [insert date of service]. [Insert drug name] has been approved by the FDA for [insert disease]. You have indicated that [insert drug name] is not covered by [insert insurance company] because [insert reason for denial from Explanation of Benefits]. [Provide a brief description of the patient’s medical history, treatments, and response to drug treatment.] [Insert patient name] has had a diagnosis of [insert diagnosis] since [insert date] at the age of [insert age]. I have administered [insert drug name] to [insert patient name] as a medically necessary part of [his/her] treatment. I would appreciate a reconsideration of the claim from [insert date of service] for [insert patient name]. To further support the medical necessity of this patient’s treatment with [insert drug name], I am including the following information: [Bullet out a list of the documentation provided with the request such as product information, clinical literature, and information from the patient’s medical record] Based on this patient’s diagnosis, disease severity, and medical history, I believe that [insert drug name] is appropriate and medically necessary for this patient, and would appreciate a reconsideration of this service. If you have any further questions, please contact me at [insert phone number] to discuss. Thank you in advance for your immediate attention to this request for treatment. Sincerely,  

[Insert physician name, practice name, and address] [Attach supporting documentation such as MRI results, chart notes, etc]

Please see full Prescribing Information, including Boxed Warning, as well as Important Safety Information about TYSABRI on pages 66-70. - 41 -

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REFERENCES 1. ICD-10 code lookup. Centers for Medicare & Medicaid Services website. https://www.cms.gov/medicare-coverage-database/staticpages/icd-10-code-lookup.aspx?KeyWord= G35&bc=AAAAAAAAAAACAA%3d%3d&. Accessed September 21, 2015. 2. ICD-10: quick start guide. Centers for Medicare & Medicaid Services website. https://www.cms.gov/Medicare/Coding/ICD10/Downloads/ICD10QuickStartGuide20150622.pdf. Accessed September 21, 2015. 3. The ICD-10 transition: an introduction. Centers for Medicare & Medicaid Services website. https://www.cms.gov/Medicare/Coding/ICD10/ Downloads/CD10Introduction20140819.pdf. Accessed September 21, 2015. 4. ICD-10. Centers for Medicare & Medicaid Services website. https://www.cms.gov/Medicare/Coding/ICD10/Index.html. Accessed September 21, 2015. 5. J Codes. HCPCS.INFO. http://www.hcpcs.info/J_Codes/default.htm. Accessed September 21, 2015. 6. TYSABRI [Prescribing Information]. Cambridge, MA: Biogen; May 2015. 7. American Medical Association Code Manager. https://ocm.ama-assn.org/OCM/CPTRelativeValueSearch.do?submitbutton=accept. Accessed September 21, 2015. 8. 2015 ICD-9-CM diagnosis code 340. ICD9Data.com website. http://www.icd9data.com/2015/Volume1/320-389/340-349/340/340.htm. Accessed September 21 2015. 9. ICD-10-CM/PCS frequently asked questions. Centers for Medicare & Medicaid Services website. https://www.cms.gov/Medicare/Coding/ICD10/Frequently-Asked-Questions.html. Accessed September 21, 2015. 10.CMS-1500 Claim form crosswalk to EMC loops and segments. Noridian Healthcare Solutions website. https://med.noridianmedicare.com/web/jeb/topics/claim-submission/ cms-1500-crosswalk-emc-loops-segments. Accessed September 21, 2015. 11.CMS manual system: Medicare claims processing. Pub. 100-04. Centers for Medicare & Medicaid Services website. http://www.cms.gov/Regulations-and-Guidance/Guidance/ Transmittals/downloads/r167cp.pdf. Accessed September 21, 2015. 12. A  NSI 837I version 5010A2 Institutional Health Care Claim to the CMS-1450 claim form crosswalk. Palmetto GBA website. http://www.palmettogba.com/Palmetto/Providers.Nsf/ files/EDI_ANSI_837I_v5010A2_crosswalk.pdf/$File/EDI_ANSI_837I_v5010A2_crosswalk.pdf. Accessed September 21, 2015. 13. O  PPS continues ASP-plus-6% reimbursement rate for 2014. American Society of Health-System Pharmacists website. https://www.ashp.org/menu/News/PharmacyNews/ NewsArticle.aspx?id=3999. Accessed September 21, 2015. 14. Medicare Part B. Plan Prescriber website. http://www.planprescriber.com/medicare-part-b/. Accessed September 21, 2015. 15. CMS Medicare FFS Provider e-News. Centers for Medicare & Medicaid Services website. http://www.cms.gov/Outreach-and-Education/Outreach/FFSProvPartProg/Downloads/ 2013-03-08-standalone.pdf. Accessed September 21, 2015. 16. Sequestration delivers cuts to family physicians, education programs. American Academy of Family Physicians website. http://www.aafp.org/news/government-medicine/20130403sequesteroutcomes.html. Accessed September 21, 2015.

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Patient Patient Support Support

PATIENT SUPPORT: ABOVE MS™ TM

Support. Elevated.

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UNDERSTANDING PATIENT FINANCIAL RESPONSIBILITY Above MS™ provides many resources to help your patients gain access to TYSABRI® (natalizumab). In addition to providing assistance with Benefit Investigations and Prior Authorizations, Above MS can help with patients’ concerns related to cost or insurance. Most patients will have either a copay or coinsurance responsibility for the drug and the administration of TYSABRI. Above MS offers personalized assistance to identify the best financial assistance option for your patients. The goal of Above MS is to ensure that no patient has to forego Biogen™ treatment due solely to financial limitations. Your office can contact a Support Coordinator from Above MS by calling 1-800-456-2255.

Copay

Coinsurance

Deductible

Typically, copay is a flat fee that patients pay each time they receive medical care. The copay may be in addition to other out-ofpocket costs, such as deductibles and coinsurance, and it varies by benefit structure.

A beneficiary cost-sharing amount that begins after the deductible is paid, coinsurance is typically based on a percentage of the cost of services, and it varies by payer.

A predetermined amount of money that the patient must spend before their payer benefits take effect.

Please see full Prescribing Information, including Boxed Warning, as well as Important Safety Information about TYSABRI on pages 66-70. - 44 -

Maximum Out-of-Pocket (OOP) Costs An annual limitation on all costsharing for which patients are responsible under a health insurance plan. This limit does not apply to premiums, balancebilled charges from out-of-network healthcare providers, or services that are not covered by the plan.

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PROVIDING FINANCIAL ASSISTANCE THROUGH ABOVE MS™ Biogen™ is committed to providing your patients with quality support services to help make their experience with TYSABRI® (natalizumab) a positive one. Biogen provides comprehensive support through: FINANCIAL ASSISTANCE

INSURANCE ASSISTANCE

$0 Copay Program from Biogen: Offering treatment for just $0 a month for eligible patients, regardless of income

Benefit Investigation: Review insurance coverage and provide assistance with prior authorizations and denied claims

Infusion Copay Assistance Program: Assistance with the cost of infusion administration for eligible patients

Insurance Counseling: Support identifying coverage options such as Medigap, COBRA, Medicaid, or options through the Health Insurance Marketplaces (HIMs)

Free Drug Program: Providing therapy to eligible patients free of charge, with no time limit to those truly in need Charitable Funding: Finding your patients assistance with premiums, copays, and other needs

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Ordering TYSABRI

Patient Patient Support Support

Claims Information for TYSABRI

Healthcare Reform

Important Safety Information

FAQs and Glossary

ABOVE MS™ FINANCIAL ASSISTANCE PROCESS • Review insurance coverage • Assistance with Prior Authorizations and Denied Claims

Benefit Investigation En

• $0 Copay Program from Biogen™ for privately insured eligible patients • Infusion Copay Assistance for eligible patients

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Insurance Counseling Free Drug

• Support finding premium, copay, and transportation assistance

• Support identifying coverage options such as Medigap, COBRA, Medicaid, or options through the Health Insurance Marketplaces (HIMs) • Free drug to those truly in need – Medicare

– Uninsured

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INITIATING THE $0 COPAY PROGRAM FROM BIOGEN This program covers the cost of the drug only and does not cover infusion-related costs.

How It Works and What Your Patients Need to Do* Have your patients contact Above MS™ to learn about enrolling in the $0 Copay Program from Biogen™

For TYSABRI® (natalizumab) obtained through a specialty pharmacy: No action is necessary on the part of the infusion site.

For TYSABRI obtained through Buy-and-Bill: If the patient qualifies for copay assistance, your office will receive a fax from the TOUCH® Prescribing Program notifying you of the patient’s eligibility. Keep the fax, because it has information that your office will need each month for administering the copay assistance.†

*Eligibility: Depending on income or, in some cases, if medication is obtained from an out-of-network provider, there may be an annual cap that limits the amount of assistance that your patient can receive over 1 year. Federal and state laws and other factors may prevent or otherwise restrict eligibility. People covered by Medicare, Medicaid, the VA/DoD, or any other federal plans are not eligible to enroll.  our office can check the specific programs that patients may be using to receive their TYSABRI using TOUCH On-Line. TOUCH On-Line lists all Y of the Above MS programs that a TYSABRI patient is currently enrolled in.

†

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INITIATING THE $0 COPAY PROGRAM FROM BIOGEN (CONT’D) For TYSABRI® (natalizumab) Obtained Through Buy-and-Bill:

Step 1

Confirm that patient is enrolled in the $0 Copay Program from Biogen™

Confirm that patient is enrolled in the $0 Copay Program from Biogen at every infusion. This information is available in TOUCH®On-Line.

Step 2

Fax an Explanation of Benefits (EOB) to Biogen

Fax an EOB to Above MS™ at 1-866-291-6114 after each infusion.*

Step 3

Charge appropriate account

Upon receipt of the Copay AUTHORIZATION FAX from Biogen, charge the copay to the authorized credit card account.

*Eligibility: Depending on income or, in some cases, if medication is obtained from an out-of-network provider, there may be an annual cap that limits the amount of assistance that your patient can receive over 1 year. Federal and state laws and other factors may prevent or otherwise restrict eligibility. People covered by Medicare, Medicaid, the VA/DoD, or any other federal plans are not eligible to enroll.

For more information on financial assistance for TYSABRI, please call 1-800-456-2255 to speak with a Support Coordinator from Above MS.

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INITIATING INFUSION COPAY ASSISTANCE This program covers the cost of the infusion only and does not cover the cost of the drug. Your office can check the specific programs that patients may be using to receive their TYSABRI® (natalizumab) using TOUCH® On-Line. TOUCH On-Line lists all of the Above MS™ programs that a TYSABRI patient is currently enrolled in.

INSURED PATIENTS*

UNINSURED PATIENTS*

1. Site of Care (SOC) infuses patient and files insurance claim.

1. S  OC infuses patient and generates detailed statement of infusion administration charges.

2. A  fter receiving Explanation of Benefits (EOB), fax to Above MS at 1-866-291-6114 after each infusion.

2. Fax detailed statement of infusion administration charges to Above MS at 1-866-291-6114 after each infusion.

3. U  pon receipt of Program AUTHORIZATION FAX from Biogen™, charge out-of-pocket (OOP) cost up to $100 to VISA account provided. Up to $100 per infusion.†

3. U  pon receipt of Program AUTHORIZATION FAX from Biogen, charge cost of infusion administration up to $100 to VISA account provided. Up to $100 per infusion.†

*People covered by any federal healthcare program—including, but not limited to, Medicare, Medicaid, the VA/DoD, TRICARE, and/or state medical or pharmaceutical assistance programs—are not eligible. Up to $1300 per year.

†

For more information on financial assistance for TYSABRI, please call 1-800-456-2255 to speak with a Support Coordinator from Above MS.

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Health Healthcare Care Health Healthcare Care Reform Reform

FAQs and Glossary

Important Safety Information

HEALTHCARE REFORM Refer to HealthCare.gov for more information. This link will take you to a website that is outside the control of Biogen™. We provide links as a public service and for informational purposes only.

Please see full Prescribing Information, including Boxed Warning, as well as Important Safety Information about TYSABRI on pages 66-70.

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HEALTHCARE REFORM On March 23, 2010, the Affordable Care Act (ACA) was signed into law to improve the insurance options available for individuals and small employers, and to reduce the number of uninsured in the United States. Included below are some key parts of the ACA that were implemented beginning January 1, 2014.1,2

Principles of Healthcare Reform and the Key Goals of the ACA Healthcare reform was founded on 4 principles1:

Improve health insurance markets

Reduce the number of uninsured

Improve quality of care

Control costs

Refer to HealthCare.gov for more information. This link will take you to a website that is outside the control of Biogen™. We provide links as a public service and for informational purposes only. Please see full Prescribing Information, including Boxed Warning, as well as Important Safety Information about TYSABRI on pages 66-70. - 51 -

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HEALTHCARE REFORM (CONT’D) The following table illustrates the primary objectives of the ACA:

Key Goals of the Affordable Care Act INSURANCE FOR INDIVIDUALS AND SMALL GROUPS

REDUCE THE NUMBER OF UNINSURED

Health Insurance Marketplaces (HIMs) enable comparison shopping3

• Subsidies for buying insurance6

Insurance sold in HIMs must meet certain standards3

• Penalty for not having insurance7

•N  o excluding patients based on pre-existing conditions2

• States have the option to expand Medicaid8

• No dropping patients without cause if they become sick4 • No lifetime or annual limits4 •M  ust offer: – Minimum required essential health benefits (EHBs)3 – Annual out-of-pocket maximums5 For more information about the Health Insurance Marketplace, please visit HealthCare.gov. This link will take you to a website that is outside the control of Biogen™. We provide links as a public service and for informational purposes only.

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ESSENTIAL HEALTH BENEFITS Plans offered in the Health Insurance Marketplace must provide essential health benefits (EHBs) to their customers. These include but are not limited to3:

Ambulatory services

Emergency services

Hospitalization

Prescription drugs

Chronic-disease management

Laboratory services

Plans may provide benefits in excess of the EHBs if they choose. However, it is important to note that MRIs are NOT included in the list of EHBs. Patients who are covered through an HIM may not be covered for MRIs. Patients should confirm that an MRI is a covered benefit under their plan.3

Refer to HealthCare.gov for more information. This link will take you to a website that is outside the control of Biogen™. We provide links as a public service and for informational purposes only.

Please see full Prescribing Information, including Boxed Warning, as well as Important Safety Information about TYSABRI on pages 66-70. - 53 -

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HELPFUL INFORMATION FOR PROVIDERS Coverage among plans in the Health Insurance Marketplace differs from traditional payer models. We have compiled some of those differences and the information that your office may need to acquire to try to ensure that your patients’ treatment and care continue.

IMPORTANT INFORMATION THAT YOUR OFFICE MAY NEED RELATING TO THE AFFORDABLE CARE ACT Marketplace plans tend to have smaller provider networks9

• A  m I in my existing patients’ new networks? • Which hospitals are in my patients’ networks? •W  hich infusion sites are in my patients’ networks?

Many patients will have plans with high out-of-pocket costs10

• What will my patients’ out-of-pocket costs be? Can they afford to pay? •A  re my patients’ MRIs, which are not an EHB, covered? • Is drug copay assistance available for patients?

Refer to HealthCare.gov for more information. This link will take you to a website that is outside the control of Biogen™. We provide links as a public service and for informational purposes only.

Please see full Prescribing Information, including Boxed Warning, as well as Important Safety Information about TYSABRI on pages 66-70. - 54 -

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FAQs and Glossary

QUESTIONS THAT YOUR PATIENTS MAY ASK ABOUT THE HEALTH INSURANCE MARKETPLACE Patients who receive their coverage from a plan in the Health Insurance Marketplace may have many questions regarding their access and coverage. Below are some frequently asked questions that patients have about the Health Insurance Marketplace. ACCESS TO PROVIDERS •A  re the patient’s providers in network? –P  atient should call their providers to confirm •W  hich hospitals are in the network? •W  ill the plan require a referral to see a specialist?

COVERED BENEFITS AND COSTS •W  hat is the copay for doctor visits? •W  hat is the copay for infusions? –P  atient should call their providers to inquire •A  re there limits on the number of services the patient may receive per year? •A  re the services that the patient expects to need covered by the plan?

COVERAGE FOR PRESCRIPTION MEDICATIONS •W  hat are the options if the provider prescribes an off-formulary drug? •A  re the patient’s medications covered on formulary? On what tier? What are the copay/coinsurance amounts? • Is drug copay assistance available for the patient’s therapies?

•P  atients should calculate their expected medical costs for the year and select the plan that best meets their costs and needs Biogen™ has a team prepared to help patients and providers become familiar with insurance options available as a result of the Affordable Care Act. Each patient’s situation differs based on the state where they reside, the plans offered in that state, and other health conditions facing the patient and/ or family. It is important that patients are educated on the options and that they make the right decision for themselves and their families.

Refer to HealthCare.gov for more information. This link will take you to a website that is outside the control of Biogen. We provide links as a public service and for informational purposes only. Please see full Prescribing Information, including Boxed Warning, as well as Important Safety Information about TYSABRI on pages 66-70. - 55 -

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HEALTHCARE REFORM RESOURCES Below are healthcare-related websites that may assist you and your patients with questions about Healthcare Reform, such as choosing insurance from the Health Insurance Marketplace, determining whether their treatment is covered by their plan, and finding answers and resources to assist with costs related to their treatment. If a patient is already enrolled, a good place to start is with the health plan website.

HealthCare.gov

National Multiple Sclerosis Society

Understanding the Affordable Care Act

These links will take you to websites that are outside the control of Biogen™. We provide links as a public service and for informational purposes only.

Please see full Prescribing Information, including Boxed Warning, as well as Important Safety Information about TYSABRI on pages 66-70. - 56 -

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Healthcare Healthcare Reform Reform

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FAQs and Glossary

REFERENCES  1. US Department of Health and Human Services. Key features of the affordable care act. HHS.gov/HealthCare website. http://www.hhs.gov/ healthcare/facts/timeline/index.html. Accessed September 21, 2015.  2. US Department of Health and Human Services. Pre-existing conditions. HHS.gov/HealthCare website. http://www.hhs.gov/healthcare/rights/preexisting/pre-existing-conditions.html. Accessed September 21, 2015.  3. What does marketplace health insurance cover? HealthCare.gov website. https://www.healthcare.gov/what-does-marketplace-health-insurancecover. Accessed September 21, 2015.   4. H  ealthcare coverage rights and protections. HealthCare.gov website. https://www.healthcare.gov/health-care-law-protections/. Accessed September 21, 2015.  5. Out-of-pocket costs. HealthCare.gov website. https://www.healthcare.gov/choose-a-plan/out-of-pocket-costs/. Accessed September 21, 2015.  6. How to save on monthly insurance premiums. HealthCare.gov website. https://www.healthcare.gov/lower-costs/save-on-monthly-premiums/. Accessed September 21, 2015.   7. T he fee you pay if you don’t have health coverage. HealthCare.gov website. https://www.healthcare.gov/fees-exemptions/fee-for-not-being-covered/. Accessed September 21, 2015.  8. Medicaid expansion & what it means for you. HealthCare.gov website. https://www.healthcare.gov/medicaid-chip/medicaid-expansion-and-you/. Accessed September 21, 2015.

Please see full Prescribing Information, including Boxed Warning, as well as Important Safety Information about TYSABRI on pages 66-70. - 57 -

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Prescribing TYSABRI

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Claims Information for TYSABRI

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Healthcare Reform

FAQs FAQs and Glossary Glossary

Important Safety Information

FREQUENTLY ASKED QUESTIONS AND GLOSSARY

Please see full Prescribing Information, including Boxed Warning, as well as Important Safety Information about TYSABRI on pages 66-70.

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FREQUENTLY ASKED QUESTIONS (FAQs) Can I report evaluation and management (E/M) services in addition to an infusion?

99215

In some instances, you may provide an E/M service in addition to the infusion within the physician office (office visit) or hospital outpatient (clinic visit). A separate and identifiable procedure must be performed in order to bill for an E/M service in addition to the drug infusion. To bill for both services, the additional service must be clearly documented in the patient’s medical record. Some payers will also require the use of the -25 modifier, which tells the payer that the additional services were performed within the same visit. If the payer allows you to bill for an E/M code in addition to the drug infusion, there are many factors that you should consider in determining which E/M code to use: • Patient status (new or established)

• Complexity of the case

• Level of decision-making required

• Time spent with the patient

The level of clinic visit billed is based on the level of service documented in the patient’s medical record and on the 1995 or 1997 E/M guidelines used by your facility to select the appropriate E/M code for clinic visits. Medicare does not pay for 99211 separately when reported on the same day as a drug-infusion service. The table to the right provides a summary of some of the E/M codes that providers may use.

Please see full Prescribing Information, including Boxed Warning, as well as Important Safety Information about TYSABRI on pages 66-70. - 59 -

99214

99213

E/M of an established patient requires 2 of these 3 key components • A comprehensive history • A comprehensive examination •M  edical decision-making of high complexity

E/M of an established patient requires 2 of these 3 key components • A comprehensive history • A comprehensive examination •M  edical decision-making of moderate complexity

E/M of an established patient requires 2 of these 3 key components • A detailed history • A detailed examination •M  edical decision-making of low complexity

99212

E/M of an established patient requires 2 of these 3 key components • An expanded focused history • An expanded focused examination •S  traightforward medical decision-making

99211

E/M of an established patient that may not require the presence of a physician. Usually, the presenting problem(s) are minimal. Typically, 5 minutes are spent performing or supervising these services.

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FREQUENTLY ASKED QUESTIONS (FAQs) (CONT’D) How do I submit a claim for an infusion of TYSABRI® (natalizumab) when I did not purchase the drug? If you have received TYSABRI at no cost (for example, either through a specialty pharmacy or through the Above MS™ program), you may not bill third-party payers for it. Although you may not bill for the drug, you may be able to bill for the administration service. Some payers may require you to enter the J-code on the claim form with a zero charge to identify which drug was administered. To verify if there are special billing guidelines for a drug obtained at no charge, it is important to check with the specific payer.

Does the patient authorization from the TOUCH® Prescribing Program have anything to do with the patient’s insurance coverage? No. It means that the patient has been authorized to receive TYSABRI. It is NOT an authorization from the insurance company; nor does it address any reimbursement-related issue.

How frequently will payers allow an infusion of TYSABRI to be given? This varies according to the guidance published by specific payers. It is important to check with the payer regarding their policy. The recommended dose of TYSABRI is 300 mg administered intravenously once every 4 weeks. What should I do if I drop a vial? Contact your specialty pharmacy or distributor and Above MS or your Infusion Reimbursement Account Manager to get more information on replacement vials.

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FREQUENTLY ASKED QUESTIONS (FAQs) (CONT’D) I received a denial because we infused the drug when the Prior Authorization was “pending.” Now what do we do? For more information on appealing claims and options for patient assistance, contact Above MS™ or your Infusion Reimbursement Account Manager.

What can I do if the Prior Authorization gets denied? For help in determining the reason(s) for denial and to explore possible options for patient assistance, contact Above MS.

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GLOSSARY Ambulatory Payment Medicare-reimbursement methodology for hospital outpatient facilities. Medicare assigns a fixed payment to group Classification: procedures that are comparable clinically and in terms of resource costs.1 Average Sales Price: Medicare-reimbursement methodology for Part B–covered drugs. ASP is the sum of gross sales less certain discounts, drawbacks, and rebates divided by the total number of units sold in the United States. Manufacturers submit ASP data to CMS by specific deadlines after the end of each quarterly period.2 Coinsurance: A beneficiary cost-sharing amount that begins after the deductible is paid, coinsurance is typically based on a percentage of the cost of services, and it varies by payer.3 Copay: A copay is a flat fee that patients pay each time they receive medical care. The copay may be in addition to other out-ofpocket costs, such as deductibles and coinsurance, and it varies by benefit structure.4 Cost Sharing: The cost for medical care that the patient pays (eg, copay, coinsurance, or deductible).3 Deductible: A predetermined amount of money that the patient must spend before their payer benefits take effect.3 Explanation of Benefits: Document received from the payer detailing specific reimbursement amounts for services rendered.5

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GLOSSARY

Claims Information for TYSABRI

Patient Support

Healthcare Reform

FAQs FAQs and Glossary Glossary

Important Safety Information

(CONT’D)

Maximum An annual limitation on all cost sharing for which patients are responsible under a health insurance plan. This limit does Out-of-Pocket Costs: not apply to premiums, balance-billed charges from out-of-network healthcare providers, or services that are not covered by the plan.3 Modifier: 2-digit numeric or alpha code used with another code to indicate that a service or procedure has been altered but is not changed in its definition or code.6 Pre-Certification: Some health insurers require pre-approval, also known as Pre-Certification, for certain types of healthcare services such as surgery or hospital visits. This means that the physician or patient must contact the insurer to obtain their approval before receiving care; otherwise, the insurer may not cover it. Not all services will require pre-approval, but when in doubt, it is best to contact the insurance company before providing any type of healthcare.7 Prior Authorization: A requirement that the physician obtain approval from a payer to prescribe a specific medication. Without this prior approval, a payer may not provide coverage or may not pay for a medication for a patient.8 Specialty Pharmacy: Distribution channel equipped to dispense specialty pharmaceuticals, which carry a unique set of needs relative to care management, reimbursement, shipping, and storage.9 Summary of Benefits: Document received from Biogen’s Above MS™ detailing Benefit Investigation information.

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Important Safety Information

REFERENCES 1. CMS manual system: Medicare claims processing. Pub. 100-04. Centers for Medicare & Medicaid Services website. http://www.cms.gov/ Regulations-and-Guidance/Guidance/Transmittals/Downloads/R167CP.pdf. Accessed September 21, 2015. 2. Social Security Act Section 1847A. Social Security Online website. http://www.ssa.gov/OP_Home/ssact/title18/1847A.htm. Accessed September 21, 2015. 3. CMS Glossary. Centers for Medicare & Medicaid Services website. http://www.cms.gov/apps/glossary/. Accessed September 21, 2015. 4. What is copay, coinsurance and deductible? Medical Billing and Coding Services website. http://www.medical-billing-coding.org/Content246.htm. Accessed September 21, 2015. 5. Explanation of benefits. Patient Advocate website. http://www.patientadvocate.org/index.php?p=441. Accessed September 21, 2015. 6. The Medical Dictionary. Modifier. Medical dictionary website. http://medical-dictionary.thefreedictionary.com/modifier. Accessed September 21, 2015. 7. The Medical Dictionary. Precertification. Medical dictionary website. http://medical-dictionary.thefreedictionary.com/precertification. Accessed September 21, 2015. 8. T he Medical Dictionary. Prior authorization. Medical dictionary website. http://medical-dictionary.thefreedictionary.com/prior+authorization. Accessed September 21, 2015. 9. What Is a specialty pharmacy? Healthworks Collective website. http://healthworkscollective.com/linda-ringquist/110611/what-specialtypharmacy. Accessed September 21, 2015.

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IMPORTANT SAFETY INFORMATION

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IMPORTANT SAFETY INFORMATION Indication TYSABRI® (natalizumab) is indicated as monotherapy for the treatment of patients with relapsing forms of multiple sclerosis. TYSABRI increases the risk of PML. When initiating and continuing treatment with TYSABRI, physicians should consider whether the expected benefit of TYSABRI is sufficient to offset this risk. See Important Safety Information regarding the risk of PML with TYSABRI. IMPORTANT SAFETY INFORMATION WARNING: Progressive Multifocal Leukoencephalopathy (PML) TYSABRI® (natalizumab) increases the risk of PML, an opportunistic viral infection of the brain that usually leads to death or severe disability. Risk factors for the development of PML include duration of therapy, prior use of immunosuppressants, and presence of anti-JCV antibodies. These factors should be considered in the context of expected benefit when initiating and continuing treatment with TYSABRI. Healthcare professionals should monitor patients on TYSABRI for any new sign or symptom that may be suggestive of PML. TYSABRI dosing should be withheld immediately at the first sign or symptom suggestive of PML. For diagnosis, an evaluation including a gadolinium-enhanced MRI scan of the brain and, when indicated, cerebrospinal fluid analysis for JC viral DNA are recommended. Because of the risk of PML, TYSABRI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the TOUCH Prescribing Program. • Infection by the JC Virus (JCV) is required for the development of PML. • There are no known interventions that can reliably prevent PML or that can adequately treat PML if it occurs. It is not known whether early detection of PML and discontinuation of TYSABRI will mitigate the disease. • PML has been reported after discontinuation of TYSABRI in patients who did not have findings suggestive of PML at the time of discontinuation. Patients should continue to be monitored for any new signs or symptoms that may be suggestive of PML for approximately 6 months after discontinuation of TYSABRI.

Please see full Prescribing Information, including Boxed Warning.

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Important Safety Information

IMPORTANT SAFETY INFORMATION (CONT’D) • Adverse events that may occur during plasma exchange include clearance of other medications and volume shifts, which have the potential to lead to hypotension or pulmonary edema. Although plasma exchange has not been studied in TYSABRI-treated patients with PML, it has been used in such patients in the postmarketing setting to remove TYSABRI more quickly from the circulation. • Immune reconstitution inflammatory syndrome (IRIS) has been reported in the majority of TYSABRI-treated patients who developed PML and subsequently discontinued TYSABRI. In almost all cases, IRIS occurred after plasma exchange was used to eliminate circulating TYSABRI. It presents as a clinical decline in the patient’s condition after TYSABRI removal (and, in some cases, after apparent clinical improvement) that may be rapid, can lead to serious neurological complications or death, and is often associated with characteristic changes in the MRI. TYSABRI has not been associated with IRIS in patients discontinuing treatment with TYSABRI for reasons unrelated to PML. In TYSABRI-treated patients with PML, IRIS has been reported within days to several weeks after plasma exchange. Monitoring for development of IRIS and appropriate treatment of the associated inflammation should be undertaken. Contraindications • TYSABRI is contraindicated in patients who have or have had PML. • TYSABRI is contraindicated in patients who have had a hypersensitivity reaction to TYSABRI. TYSABRI TOUCH Prescribing Program • Because of the risk of PML, TYSABRI is available only through a restricted distribution program under a REMS called the TOUCH® Prescribing Program. • Patients must be enrolled in the TOUCH Prescribing Program, read the Medication Guide, understand the risks associated with TYSABRI and complete and sign the Patient-Prescriber Enrollment Form.

Please see full Prescribing Information, including Boxed Warning.

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IMPORTANT SAFETY INFORMATION (CONT’D) Herpes Encephalitis and Meningitis • TYSABRI increases the risk of developing encephalitis and meningitis caused by herpes simplex and varicella zoster viruses. • Serious, life-threatening, and sometimes fatal cases have been reported in the postmarketing setting in multiple sclerosis patients receiving TYSABRI. • The duration of treatment with TYSABRI prior to onset ranged from a few months to several years. • Monitor patients receiving TYSABRI for signs and symptoms of meningitis and encephalitis. If herpes encephalitis or meningitis occurs, TYSABRI should be discontinued, and appropriate treatment for herpes encephalitis/meningitis should be administered. Hepatotoxicity • Clinically significant liver injury, including acute liver failure requiring transplant, has been reported in patients treated with TYSABRI in the postmarketing setting. • Signs of liver injury, including markedly elevated serum hepatic enzymes and elevated total bilirubin, occurred as early as six days after the first dose; signs of liver injury have also been reported for the first time after multiple doses. • TYSABRI should be discontinued in patients with jaundice or other evidence of significant liver injury (e.g., laboratory evidence). Hypersensitivity/Antibody Formation • Hypersensitivity reactions have occurred in patients receiving TYSABRI, including serious systemic reactions (e.g., anaphylaxis) which occurred at an incidence of <1%. • Reactions usually occur within 2 hours of the start of the infusion. Symptoms associated with these reactions can include urticaria, dizziness, fever, rash, rigors, pruritus, nausea, flushing, hypotension, dyspnea, and chest pain. • If a hypersensitivity reaction occurs, discontinue administration of TYSABRI and initiate appropriate therapy. Patients who experience a hypersensitivity reaction should not be re-treated with TYSABRI. • Hypersensitivity reactions were more frequent in patients with antibodies to TYSABRI compared with patients who did not develop antibodies to TYSABRI in both MS and CD studies • Patients who receive TYSABRI after an extended period without treatment may be at higher risk of hypersensitivity reactions.

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IMPORTANT SAFETY INFORMATION (CONT’D) Immunosuppression/Infections • The immune system effects of TYSABRI may increase the risk for infections. • In Study MS1, certain types of infections—including pneumonias and urinary tract infections (including serious cases), gastroenteritis, vaginal infections, tooth infections, tonsillitis, and herpes infections—occurred more often in TYSABRI-treated patients than in placebo-treated patients. One opportunistic infection, a cryptosporidial gastroenteritis with a prolonged course, was observed in a patient who received TYSABRI in Study MS1. • In Studies MS1 and MS2, an increase in infections was seen in patients concurrently receiving short courses of corticosteroids. However, the increase in infections in TYSABRI-treated patients who received steroids was similar to the increase in placebo-treated patients who received steroids. • Concurrent use of antineoplastic, immunosuppressant, or immunomodulating agents may further increase the risk of infections over the risk observed with use of TYSABRI alone. • In Studies MS1 and MS2, the rate of any type of infection was approximately 1.5 per patient-year in both TYSABRI-treated patients and placebotreated patients. • In Study MS1, the incidence of serious infections was approximately 3% in TYSABRI-treated patients and in placebo-treated patients. Most patients did not interrupt treatment with TYSABRI during infections. Laboratory Test Abnormalities • In clinical trials, TYSABRI was observed to induce increases in circulating lymphocytes, monocytes, eosinophils, basophils, and nucleated red blood cells. Observed changes persisted during TYSABRI exposure, but were reversible, returning to baseline levels usually within 16 weeks after the last dose. Elevations of neutrophils were not observed. TYSABRI induces mild decreases in hemoglobin levels that are frequently transient.

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IMPORTANT SAFETY INFORMATION (CONT’D) Adverse Reactions • The most common adverse reactions reported at an incidence of ≥10% with TYSABRI and ≥2% difference with placebo were headache (38% vs 33%), fatigue (27% vs 21%), infusion reactions (24% vs 18%), urinary tract infections (21% vs 17%), arthralgia (19% vs 14%), depression (19% vs 16%), pain in extremity (16% vs 14%), rash (12% vs 9%), gastroenteritis (11% vs 9%), and vaginitis (10% vs 6%). • The most frequently reported serious adverse reactions in Study MS1 were infections (3.2% vs 2.6% placebo), including urinary tract infection (0.8% vs 0.3%) and pneumonia (0.6% vs 0%), acute hypersensitivity reactions (1.1% vs 0.3%, including anaphylaxis/anaphylactoid reaction [0.8% vs 0%]), depression (1.0% vs 1.0%, including suicidal ideation or attempt [0.6% vs 0.3%]), and cholelithiasis (1.0% vs 0.3%). • Based on animal data, TYSABRI may cause fetal harm. TYSABRI should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

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Please see full Prescribing Information, including Boxed Warning, as well as Important Safety Information about TYSABRI on pages 66-70.

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10/15

TYS-US-0631

DECISIVE ACTION MATTERS