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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-J2000-70

Original Effective Date: 03/15/17

Reviewed: 02/08/17

Revised: 00/00/00

Subject: Nusinersen (Spinraza™)

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.

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

DESCRIPTION:

Spinal muscular atrophy (SMA) is a group of genetic disorders characterized by a loss of motor neurons. While there are numerous gene mutations that can cause the different forms of SMA, 95% of cases result from a homozygous deletion or mutation in the 5q13 survival of motor neuron (SMN1) gene. This deficiency results in degeneration of motor neurons causing muscle atrophy, particularly in the limbs and the muscles that control the mouth, throat and respiration. A second gene, SMN2, is nearly identical to SMN1 but does not produce much functional (i.e., full length, stable) SMN protein. While there is generally one SMN1 per chromosome, there is a variable number of SMN2 gene copies.

The severity of SMA (an autosomal recessive disorder) is highly variable and correlates mainly with the number of SMN2 gene copies. The clinical features can be classified based on the age of onset and maximum motor function (table 1).

Table 1. SMA Classification

Type

Age of onset

Highest Function

Natural Age of Death

Copies of SMN2

0

Prenatal

Respiratory failure

< 1 month

1

I (Werdnig-Hoffman disease)

0-6 months

Never sit

< 2 years

2

II (Dubowitz disease)

< 18 months

Never stand

> 2 years

3, 4

III (Kugelberg-Welander disease)

18 months-21 years

Stand or ambulatory

Adult

3, 4

IV (adult onset)

> 21 years

Ambulatory

Adult

4-8

The incidence of SMA is approximately 1 in 11,000 live births and it is reported to be the leading genetic cause of infant death. Carrier frequencies are estimated at 1 in 40 to 1 in 60. SMA can be diagnosed by DNA analysis detection of SMN1 deletion in both SMN1 alleles. This is approximately 95% sensitive (100% specific) for patients with clinical features suspicious for SMA.

There is no known cure for SMA. Treatment is designed to address the primary and secondary effects of muscle weakness and includes management of pulmonary complications, nutritional and gastrointestinal support, orthopedic care, rehabilitative interventions, and end-of-life care.

Nusinersen (Spinraza), an antisense oligonucleotide, was approved by the U.S. Food and Drug Administration (FDA) in December 2016 for the treatment of the treatment of spinal muscular atrophy (SMA) in pediatric and adult patients. The approval was based on positive interim results of a phase III, double-blind, controlled clinical trial (ENDEAR).

The safety and efficacy of nusinersen were evaluated in in infants, aged 7 months or younger at study entry, who were diagnosed with symptomatic infantile-onset SMA (Type I). Patients were required to have a confirmatory diagnosis of SMA consistent with type I severity as determined by identification of two copies of SMN2, age of onset (symptom onset before 6 months of age), and symptom severity. A total of 82 infants out of 121 enrolled were included in the interim analysis. Study participants were enrolled 2:1 and all infants included in the interim analysis had died, withdrawn or completed at least 183 days (6 months) of treatment. Baseline disease characteristics were similar between study arms with the exception of the nusinersen-treatment group having a higher percentage of paradoxical breathing, pneumonia, respiratory symptoms, swallowing/feeding difficulty and need for respiratory support. Despite the treatment group having more severe symptoms at baseline, the trial found 40% of those treated, compared with 0% of those in the control arm, demonstrated improvement in motor milestones such as head control, sitting, crawling and standing (p<0.0001). Furthermore, as assessed by the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND), 63% (n=33) of infants treated with nusinersen improved by at least 4-points, whereas only 3% (n=1) achieved this improvement in the control arm. Similarly, 40% (n=12) of the control arm worsened by at least 4-points on the CHOP-INTEND test whereas only 4% (n=2) of the treatment arms experienced this decline in motor function. The adverse events that occurred in the treatment arm more often than the control arm were respiratory infections and constipation. Atelectasis, a serious adverse reaction, was more frequent in the treatment arm (14%) compared to the control arm (5%).

Currently, there is no published clinical data regarding the safety and efficacy of nusinersen in patients with symptom onset after six months of age.

POSITION STATEMENT:

Initiation of nusinersen (Spinraza) meets the definition of medical necessity when all of the following criteria are met:

1. Indication for use is spinal muscular atrophy (SMA)

2. Member’s diagnosis has been confirmed by:

a. Homozygous deletion of SMN1 gene exon 7 (with or without deletion of exon 8) – laboratory documentation must be provided

b. Single copy of SMN1 with sequencing of the coding region to confirm a mutation rendering a homozygous dysfunction of the gene – laboratory documentation must be provided

3. Treatment is prescribed by or in consulation with a board certified neurologist

4. Dose does not exceed 12 mg x 4 doses

Approval duration: 6 months

Continuation of nusinersen (Spinraza) meets the definition of medical necessity when all of the following criteria are met:

1. Authorization/reauthorization has been previously approved by Florida Blue in the past two years for treatment of spinal muscular atrophy (SMA), OR the member has previously met all indication-specific initiation criteria

2. Member has demonstrated a beneficial response in SMA-assocated symptoms – documentation from medical record must be provided

3. Treatment is prescribed by or in consulation with a board certified neurologist

4. Dose does not exceed 12 mg every 4 months (3 doses/year)

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

• The recommended dosage is 12 mg (5 mL) per administration

• Initiate treatment with 4 loading doses; the first three loading doses should be administered at 14-day intervals; the 4th loading dose should be administered 30 days after the 3rd dose; a maintenance dose should be administered once every 4 months thereafter

Dose Adjustments

• None

Drug Availability

• Injection: 12 mg/5 mL (2.4 mg/mL) in a single-dose vial

PRECAUTIONS:

Boxed Warning

• None

Contraindications

• None

Precautions/Warnings

• Thrombocytopenia and Coagulation Abnormalities: Increased risk for bleeding complications; testing required at baseline and before each dose

• Renal Toxicity: Quantitative spot urine protein testing required at baseline and prior to each dose

BILLING/CODING INFORMATION:

The following codes may be used to describe:

HCPCS Coding

J3490

Unclassified drug

ICD-10 Diagnoses Codes That Support Medical Necessity

G12.0

Infantile spinal muscular atrophy, type I [Werdnig-Hoffmann]

G12.1

Other inherited spinal muscular atrophy

G12.8

Other spinal muscular atrophies and related syndromes

G12.9

Spinal muscular atrophy, unspecified

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

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

DEFINITIONS:

None

RELATED GUIDELINES:

None

OTHER:

None

REFERENCES:

  1. American College of Obstetricians and Gynecologists (ACOG) committee opinion 432 on spinal muscular atrophy can be found in Obstet Gynecol 2009 May;113(5):1194, reaffirmed 2014 Dec.
  2. Arnold WD, Kassar D, Kissel JT. Spinal muscular atrophy: diagnosis and management in a new therapeutic era. Muscle Nerve. 2015 Feb;51(2):157-67.
  3. Biogen. Spinraza (nusinersen) injection, for intrathecal use. 2016. [cited 02/08/17]. In: DailyMed [Internet]. Bethesda (MD): National Library of Medicine. Available from: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=dd70cd5f-b0fc-4ba4-a5ea-89a34778bd94.
  4. Clinical Pharmacology [Internet]. Tampa (FL): Gold Standard, Inc.; 2017 [cited 02/08/17]. Available from: http://www.clinicalpharmacology.com/.
  5. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine; 2000 Feb 29 - [cited 02/08/17]. Available from: http://clinicaltrials.gov/.
  6. DRUGDEX® System [Internet]. Greenwood Village (CO): Thomson Micromedex; Updated periodically [cited 02/08/17]. Available from: http://www.thomsonhc.com/.
  7. Kolb SJ, Kissel JT. Spinal Muscular Atrophy. Neurol Clin. 2015 Nov;33(4):831-46.
  8. Markowitz JA, Singh P, Darras BT. Spinal muscular atrophy: a clinical and research update. Pediatr Neurol. 2012 Jan;46(1):1-12.
  9. Mercuri E, Bertini E, Iannaccone ST. Childhood spinal muscular atrophy: controversies and challenges. Lancet Neurol. 2012 May;11(5):443-52.
  10. Orphan Drug Designations and Approval [Internet]. Silver Spring (MD): US Food and Drug Administration; 2017 [cited 02/08/17]. Available from: http://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm/.
  11. Prior TW, Russman BS. Spinal muscular atrophy. GeneReviews 2013 Nov 14
  12. Wang CH, Finkel RS, Bertini ES, et al; Participants of the International Conference on SMA Standard of Care. Consensus statement for standard of care in spinal muscular atrophy. J Child Neurol. 2007 Aug;22(8):1027-49.

COMMITTEE APPROVAL:

This Medical Coverage Guideline (MCG) was approved by the BCBSF Pharmacy Policy Committee on 02/08/17.

GUIDELINE UPDATE INFORMATION:

03/15/17

New Medical Coverage Guideline.

Date Printed: June 23, 2017: 11:37 AM