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This medical policy (medical coverage guideline) is Copyright 2017, Blue Cross and Blue Shield of Florida (BCBSF). All Rights Reserved. You may not copy or use this document or disclose its contents without the express written permission of BCBSF. The medical codes referenced in this document may be proprietary and owned by others. BCBSF makes no claim of ownership of such codes. Our use of such codes in this document is for explanation and guidance and should not be construed as a license for their use by you. Before utilizing the codes, please be sure that to the extent required, you have secured any appropriate licenses for such use. Current Procedural Terminology (CPT) is copyright 2017 American Medical Association. All Rights Reserved. No fee schedules, basic units, relative values, or related listings are included in CPT. The AMA assumes no liability for the data contained herein. Applicable FARS/DFARS restrictions apply to government use. CPT® is a trademark of the American Medical Association. The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

09-J1000-30

Original Effective Date: 01/01/11

Reviewed: 09/13/17

Revised: 10/15/17

Subject: Fingolimod (Gilenya™) Capsule

THIS MEDICAL COVERAGE GUIDELINE IS NOT AN AUTHORIZATION, CERTIFICATION, EXPLANATION OF BENEFITS, OR A GUARANTEE OF PAYMENT, NOR DOES IT SUBSTITUTE FOR OR CONSTITUTE MEDICAL ADVICE. ALL MEDICAL DECISIONS ARE SOLELY THE RESPONSIBILITY OF THE PATIENT AND PHYSICIAN. BENEFITS ARE DETERMINED BY THE GROUP CONTRACT, MEMBER BENEFIT BOOKLET, AND/OR INDIVIDUAL SUBSCRIBER CERTIFICATE IN EFFECT AT THE TIME SERVICES WERE RENDERED. THIS MEDICAL COVERAGE GUIDELINE APPLIES TO ALL LINES OF BUSINESS UNLESS OTHERWISE NOTED IN THE PROGRAM EXCEPTIONS SECTION.

           
Position Statement Dosage/ Administration Billing/Coding Reimbursement Program| Exceptions Definitions
           
Related Guidelines Other References Updates  
           

DESCRIPTION:

Multiple sclerosis (MS) is a chronic disease affecting the central nervous system (CNS). It is characterized by triad of inflammation, demyelination, and scarring of the central nervous system and manifests as pathological (immune-mediated CNS demyelination and axonal injury) and clinical (exacerbations, disability progression) dissemination in time and space. Although the clinical course of the disease is capricious, MS has been categorized into four types: relapsing-remitting (RRMS), secondary progressive (SPMS), primary progressive (PPMS), and progressive-relapsing (PRMS). The most common type is RRMS, which is characterized by acute attacks followed by periods of remission.

Fingolimod is an immunomodulatory agent that is used to reduce the frequency of relapses and delay the accumulation of physical disability in patients with RRMS. Fingolimod has a novel mechanism of action and exerts its physiologic effects through attachment to the sphingosine-1 phosphate receptor, which is plays a role in immune function regulation.

Clinical practice guidelines set forth by the American Academy of Neurology (AAN) and the Multiple Sclerosis Therapy Consensus Group (MSTCG) do not include recommendations for the use of fingolimod, as these guidelines were updated prior to the approval of fingolimod. However, both the U.S. Food and Drug Administration (FDA) and the National Multiple Sclerosis Society recognize fingolimod as a first-line therapy for the treatment of relapsing MS.

POSITION STATEMENT:

Comparative Effectiveness

The Food and Drug Administration has deemed the drug(s) or biological product(s) in this coverage policy to be appropriate for self-administration or administration by a caregiver (i.e., not a healthcare professional). Therefore, coverage (i.e., administration) in a provider-administered setting such as an outpatient hospital, ambulatory surgical suite, physician office, or emergency facility is not considered medically necessary.

NOTE: Aubagio, Avonex, Betaseron, Copaxone, Gilenya, Glatopa, Plegridy, Rebif, and Tecfidera are preferred products for treatment of relapsing forms of multiple sclerosis.

Initiation of fingolimod (Gilenya™) meets the definition of medical necessity when ALL of the following criteria are met:

1. The member is diagnosed with a relapsing form of multiple sclerosis (i.e., relapsing remitting multiple sclerosis [RRMS], secondary progressive MS [SPMS], progressive-relapsing MS [PRMS]).

2. Fingolimod will not be used in combination with ANY of the following:

a. Alemtuzumab (Lemtrada)

b. Daclizumab (Zinbryta)

c. Dimethyl fumarate (Tecfidera)

d. Glatiramer acetate (Copaxone, Glatopa)

e. Interferon beta-1a (Avonex, Rebif)

f. Interferon beta-1b (Betaseron, Extavia)

g. Mitoxantrone (Novantrone)

h. Natalizumab (Tysabri)

i. Ocrelizumab (Ocrevus)

j. Peg-interferon beta-1a (Plegridy)

k. Teriflunomide (Aubagio)

3. The member does not have any of the following:

a. History (within the last 6 months) of myocardial infarction, unstable angina, stroke, transient ischemic attack, decompensated heart failure requiring hospitalization, or NYHA Class III/IV heart failure

b. History or presence of Mobitz Type II second- or third-degree AV block or sick sinus syndrome (unless member has a functioning pacemaker)

c. Prolonged QT interval (i.e., QTc > 500 ms)

d. Concomitant therapy with a Class Ia (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol, dofetilide) anti-arrhythmic drug

4. The dosage does not exceed 0.5 mg daily.

Approval duration: 1 year

Continuation of fingolimod therapy meets the definition of medical necessity when ALL of the following criteria are met:

1. Member has demonstrated a beneficial response to therapy for treatment of a relapsing form of multiple sclerosis (i.e., relapsing remitting multiple sclerosis [RRMS], secondary progressive MS [SPMS], progressive-relapsing MS [PRMS])

2. Authorization/reauthorization for fingolimod has been previously approved by Florida Blue or another health plan in the past 2 years, OR the member currently meets all indication-specific initiation criteria

3. Fingolimod will not be in combination with ANY of the following:

a. Alemtuzumab (Lemtrada)

b. Daclizumab (Zinbryta)

c. Dimethyl fumarate (Tecfidera)

d. Glatiramer acetate (Copaxone, Glatopa)

e. Interferon beta-1a (Avonex, Rebif)

f. Interferon beta-1b (Betaseron, Extavia)

g. Mitoxantrone (Novantrone)

h. Natalizumab (Tysabri)

i. Ocrelizumab (Ocrevus)

j. Peg-interferon beta-1a (Plegridy)

k. Teriflunomide (Aubagio)

4. The dose does not exceed 0.5 mg daily.

Approval duration: 1 year

DOSAGE/ADMINISTRATION:

THIS INFORMATION IS PROVIDED FOR INFORMATIONAL PURPOSES ONLY AND SHOULD NOT BE USED AS A SOURCE FOR MAKING PRESCRIBING OR OTHER MEDICAL DETERMINATIONS. PROVIDERS SHOULD REFER TO THE MANUFACTURER’S FULL PRESCRIBING INFORMATION FOR DOSAGE GUIDELINES AND OTHER INFORMATION RELATED TO THIS MEDICATION BEFORE MAKING ANY CLINICAL DECISIONS REGARDING ITS USAGE.

FDA-Approved: Fingolimod is approved for the treatment of adult members with relapsing forms of multiple sclerosis to reduce the frequency of clinical exacerbations and to delay the accumulation of physical disability. Fingolimod should be administered as 0.5 mg capsule once daily, with or without food.

First Dose Monitoring:

• The first dose of fingolimod should be administered in a setting that has adequate resources to manage symptomatic bradycardia that occurs following initiation of treatment. The heart rate typically decreases within an hour and the Day 1 nadir generally occurs within approximately 6 hours. The nadir can be observed up to 24 hours following the first dose in some patients. Hourly pulse and blood pressure should be performed

• An ECG should be obtained prior to initiation and at end of observation period

Monitor symptomatic bradycardia with ECG until resolved. Continue overnight and repeat first-dose monitoring.

Observe patients overnight if at higher risk of symptomatic bradycardia, heart block, prolonged QTc interval, or if taking drugs with known risk of torsades de pointes.

• Additional observation should be performed if at the end of the 6-hour period if any of the following occurs:

o If the heart rate is less than 45 beats per minute;

o If the heart rate is at the lowest value at the end of the observation period;

o If the ECG shows new onset second degree or higher AV block

Re-initiation of Therapy Following Discontinuation:

• If fingolimod therapy is discontinued for more than 14 days, after the first month of the treatment, the effects on heart rate and AV conduction may recur on reintroduction and the same precautions (first dose monitoring) should apply.

• Within the first two weeks of treatment, first dose procedures are recommended after interruption of one day or more

• Within the first three or four weeks of treatment, first dose procedures are recommended after treatment interruption of more than 7 days.

Recommended Dose Adjustments:

• Hepatic Impairment

o Dosage adjustments are not indicated for members with mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment

o Fingolimod exposure is doubled in members with severe (Child-Pugh Class C) hepatic impairment; as such, fingolimod should be used cautiously in members with severe hepatic impairment. Additionally, close monitoring should be performed because the risk of adverse reactions may be greater.

• Renal Impairment: The serum concentration of some fingolimod metabolites was increased (up to 13-fold) in individuals with renal impairment. The toxicity of these metabolites has not been fully explored and the serum concentration of these metabolites has not been assessed in patients with mild or moderate renal insufficiency.

• Special Populations: The safety and efficacy of fingolimod has not been adequately evaluated in patients over the age of 65. Fingolimod should be used with caution in this population considering the higher frequency of hepatic and renal impairment. The safety and efficacy of fingolimod has not been evaluated in individuals less than 18 years of age.

Missed Dose: recommendations for missed doses are not included in the manufacturer’s labeling; see “Re-initiation of therapy following discontinuation” above for the appropriate course of action if therapy is initiated following discontinuation or if therapy is interrupted for one day or more.

Drug Availability: Fingolimod is supplied as a 0.5 mg capsule

PRECAUTIONS:

Contraindications

Fingolimod therapy is contraindicated in the following members:

• Members with a history (within the last 6 months) of myocardial infarction, unstable angina, stroke, TIA, decompensated heart failure require hospitalization or Class III/IV heart failure

• Members with a history or presence of Mobitz Type II second- or third-degree AV block or sick sinus syndrome, unless member has a functioning pacemaker

• Members with a baseline QTc interval of ≥ 500 ms

• Members prescribed concomitant Class Ia or Class III anti-arrhythmic therapy

Members with hypersensitivity to fingolimod or its excipients

Warnings/Precautions

Bradycardia and AV Block: decreases in heart rate and/or AV conduction can occur following fingolimod initiation; members should be closely monitored (see “Dosage and Administration” for additional information).

Infection: fingolimod therapy my increase the risk of infection. A recent complete blood count (CBC) should be available prior to fingolimod initiation. Members should be monitored for signs and symptoms of infection during treatment and for two months after discontinuation. Fingolimod should not be initiated in members with active acute or chronic infections. All members receiving fingolimod should receive the varicella vaccine, or have evidence of antibodies to varicella zoster virus.

Progressive multifocal leukoencephalopathy (PML): withhold at the first sign or symptom suggestive of PML

Macular edema: macular edema can occur with or without visual symptoms. An ophthalmologic evaluation should be performed before and re-evaluated at 3-4 months following fingolimod initiation. Visual acuity should be monitored at baseline and during routine evaluation of members. Members with diabetes mellitus or a history of uveitis are at an increased risk for macular edema and should have regular ophthalmologic evaluation

Posterior reversible encephalopathy syndrome (PRES): Rare cases of PRES have occurred. Symptoms may include sudden onset of severe headache, altered mental status, visual disturbances, and seizure. If suspected discontinue

Respiratory effects: fingolimod therapy has been associated with a decrease in pulmonary function tests. Spirometry and diffusion lung capacity for carbon monoxide should be obtained when clinically indicated.

Hepatic effects: fingolimod therapy has been associated with increases in liver transaminases. Liver function tests (LFTs) should be obtained prior to fingolimod initiation and assessed if hepatic injury is suspected. If significant liver injury occurs, fingolimod should be discontinued.

Pregnancy and Nursing:

• Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women; however, in oral studies conducted in rates and rabbits, fingolimod demonstrated developmental toxicity, including teratogenicity. Female members of childbearing potential should be advised to use effective contraception during and 2 months after stopping fingolimod.

• A pregnancy registry has been established to collect information about the effect of fingolimod use during pregnancy. Healthcare providers are encouraged to enroll pregnant patients, or pregnant members may register themselves in the fingolimod pregnancy registry by calling 1-877-59807237 or visiting www.gilenyapregnancyregistry.com

• Fingolimod is excreted into the milk of lactating rats and excretion into human milk is probable. No human studies have investigated the effects of fingolimod on breast-fed infants and avoidance in nursing women is recommended.

Increased blood pressure: monitor during treatment. Increases in blood pressure occurred in clinical trials as compared to placebo.

Basal cell carcinoma (BCC): suspicious skin lesions should be evaluated. An increase in the incidence of BCC occurred in clinical trials as compared to placebo.

Immune system effects following discontinuation: Fingolimod remains in the blood for up to 2 months following the last dose. Lymphocyte counts may be affected during this time and precaution is advised with initiation of other drugs during this time.

Hypersensitivity reactions: Reactions including rash, urticaria, and angioedema have been reported.

BILLING/CODING INFORMATION:

HCPCS Coding:

J8499

Prescription drug, oral, nonchemotherapeutic, NOS

ICD-10 Diagnosis Codes That Support Medical Necessity:

G35

Multiple sclerosis

REIMBURSEMENT INFORMATION:

Refer to section entitled POSITION STATEMENT.

PROGRAM EXCEPTIONS:

Federal Employee Program (FEP): Follow FEP guidelines.

State Account Organization (SAO): Follow SAO guidelines.

Medicare Advantage Products: No National Coverage Determination (NCD) and/or Local Coverage Determination (LCD) were found at the time of the last guideline revised date.

Medicare Part D: Florida Blue has delegated to Prime Therapeutics authority to make coverage determinations for the Medicare Part D services referenced in this guideline.

DEFINITIONS:

Relapsing-remitting multiple sclerosis (RRMS): Characterized by acute attacks followed by periods of remission; primary form of MS that occurs in approximately 85% of patients.

Primary-progressive multiple sclerosis (PPMS): Steadily progressive course from onset with no acute attacks; occurs in 10-15% of patients with MS.

Secondary-progressive multiple sclerosis (SPMS): An initial period of RRMS, followed by a steadily progressive course, with or without acute relapses; 75-85% of patients diagnosed with RRMS will transition to SPMS.

Progressive-relapsing multiple sclerosis (PRMS): Steadily progressive course from onset with acute attacks, with or without recovery; occurs in less than 5% of MS patients.

RELATED GUIDELINES:

Botulinum Toxins, 09-J0000-29
Diagnosis and Treatment of Chronic Cerebrospinal Venous Insufficiency in Multiple Sclerosis, 02-35000-01

Dimethyl Fumarate (Tecfidera), 09-J1000-96

Functional Neuromuscular Stimulation, 09-E0000-54

Immune Globulin Therapy, 09-J0000-06

Magnetic Resonance Imaging (MRI) Brain and Head, 04-70540-11

Multiple Sclerosis Self Injectable Therapy, 09-J1000-39

Natalizumab (Tysabri®) IV, 09-J0000-73

Ocrelizumab (Ocrevus), 09-J2000-78

Teriflunomide (Aubagio), 09-J1000-82

OTHER:

None applicable.

REFERENCES:

  1. AHFS Drug Information. Bethesda (MD): American Society of Health-System Pharmacists, Inc; 2016 [cited 2016-09-24].
  2. Bayer. Betaseron (interferon beta-1b) injection. 2014 [cited 2015-08-25]. In: DailyMed [Internet]. Bethesda (MD): National Library of Medicine. Available from: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=66311f74-0472-4fa3-848a-06002ca0def5/.
  3. Biogen. Avonex (interferon beta-1a) injection. 2008 [cited 2015-08-25]. In: DailyMed [Internet]. Bethesda (MD): National Library of Medicine. Available from: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=84d42ba4-6eef-41a7-a1d1-2cc887ef118d/.
  4. Biogen. Plegridy (peginterferon beta-1a) injection. 2014 [cited 2015-08-25]. In: DailyMed [Internet]. Bethesda (MD): National Library of Medicine. Available from: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=08f0ea03-4e6d-195d-aef4-886e32befa95/.
  5. Biogen. Tecfidera (dimethyl fumarate) capsule. 2015 [cited 2015-08-25]. In: DailyMed [Internet]. Bethesda (MD): National Library of Medicine. Available from: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=665d7e74-036c-5f68-5b67-ab84b9b49151/.
  6. Biogen. Tysabri (natalizumab) injection. 2015 [cited 2015-08-25]. In: DailyMed [Internet]. Bethesda (MD): National Library of Medicine. Available from: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c5fdde91-1989-4dd2-9129-4f3323ea2962/.
  7. Clinical Pharmacology [Internet]. Tampa (FL): Gold Standard, Inc.; 2017 [cited 2017-08-30]. Available from: http://www.clinicalpharmacology.com/.
  8. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine; 2000 Feb 29 - [cited 2015-08-25]. Available from: http://clinicaltrials.gov/.
  9. Cohen JA, Barkhof F, Comi G, et al. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. NEJM 2010; 362:402-15.
  10. DRUGDEX® System [Internet]. Greenwood Village (CO): Thomson Micromedex; Updated periodically [cited 2017-08-30]. Available from: http://www.thomsonhc.com/.
  11. EMD Serono. Rebif (interferon beta-1a) injection. 2015 [cited 2015-08-25]. In: DailyMed [Internet]. Bethesda (MD): National Library of Medicine. Available from: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c6fcb5d2-8fcd-44fa-a838-b84ee5f44f0f/.
  12. Freedman MS. Treatment options for patients with multiple sclerosis who have suboptimal response to interferon-β therapy. Eur J Neurol 2014;21:377-87.
  13. Genzyme. Aubagio (teriflunomide) tablet, film coated. 2014 [cited 2015-08-25]. In: DailyMed [Internet]. Bethesda (MD): National Library of Medicine. Available from: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4650d12c-b9c8-4525-b07f-a2d773eca155/.
  14. Limmroth V. Treatment of relapsing-remitting multiple sclerosis: current and future algorithms. Eur J Neurol 2014;72:35-8.
  15. Multiple Sclerosis Coalition. The use of disease-modifying therapies in multiple sclerosis: principles and current evidence. Available at http://www.nationalmssociety.org/getmedia/5ca284d3-fc7c-4ba5-b005-ab537d495c3c/DMT_Consensus_MS_Coalition_color. Accessed 09/26/2016.
  16. National Clinical Advisory Board of the National Multiple Sclerosis Society. Disease management consensus statement. Available at http://www.nationalmssociety.org/about-multiple-sclerosis/what-we-know-about-ms/treatments/index.aspx Accessed 08/13/2012.
  17. National Clinical Advisory Board of the National Multiple Sclerosis Society. Disease management consensus statement. Available at http://www.nationalmssociety.org/about-multiple-sclerosis/what-we-know-about-ms/treatments/index.aspx Accessed 08/13/2012.
  18. Novartis. Extavia (interferon beta-1b) injection. 2014 [cited 2015-08-25]. In: DailyMed [Internet]. Bethesda (MD): National Library of Medicine. Available from: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4cfdb571-ec4c-478f-bedc-e0669eeea504/.
  19. Novartis. Gilenya (fingolimod hydrochloride) capsule. 2017 [cited 2017-08-30]. In: DailyMed [Internet]. Bethesda (MD): National Library of Medicine. Available from: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=cc9e1c8c-0e2b-44e2-878b-27057f786be9/.
  20. Orphan Drug Designations and Approval [Internet]. Silver Spring (MD): US Food and Drug Administration; 2016 [cited 2016-09-24]. Available from: http://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm/.
  21. Sandoz. Glatopa (glatiramer acetate) injection. 2015 [cited 2015-08-25]. In: DailyMed [Internet]. Bethesda (MD): National Library of Medicine. Available from: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5f01e40a-b6f6-40fb-b37c-3d06f1428e86/.
  22. Teva. Copaxone (glatiramer acetate) injection. 2014 [cited 2015-08-25]. In: DailyMed [Internet]. Bethesda (MD): National Library of Medicine. Available from: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aa88f583-4f5f-433b-80b4-1f4c9fb28357/.
  23. Wiendl H, Toyka KV, Rieckmann R, et.al. Basic and escalating immunomodulatory treatments in multiple sclerosis: current therapeutic recommendations. J Neurol 2008;255:1449-63.
  24. Wingerchuk DM, Carter JL. Multiple sclerosis: current and emerging disease-modifying therapies and treatment strategies. Mayo Clin Proc 2014;89:225-40.

COMMITTEE APPROVAL:

This Medical Coverage Guideline (MCG) was approved by the BCBSF Pharmacy Policy Committee on 09/13/17.

GUIDELINE UPDATE INFORMATION:

01/01/11

New Medical Coverage Guideline.

06/15/11

Review and revision to guideline; consisting of updating references.

06/15/12

Review and revision to guideline; consisting of updating description, position statement, precautions, coding and references.

10/15/12

Review and revision to guideline; consisting of revising position statement and description section, updating precautions/warnings, definition, and reference sections, adding contraindications section.

10/15/13

Review and revision to guideline; consisting of revising position statement updating references.

01/01/14

Revision to guideline; consisting of updating position statement.

10/15/14

Review and revision to guideline; consisting of reformatting position statement and updating references.

01/01/15

Revision to guideline; consisting of updating position statement.

10/15/15

Review and revision to guideline; consisting of updating the position statement and references.

11/01/15

Revision: ICD-9 Codes deleted.

01/01/17

Review and revision to guideline; consisting of updating the position statement, administration, precautions and references.

10/15/17

Review and revision to guideline; consisting of updating the position statement and references.

Date Printed: December 17, 2017: 04:14 PM