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Amondys-45™ (casimersen)

Policy Number: PH-0593

 

Intravenous

Last Review Date: 05/02/2024

Date of Origin: 04/06/2021

Dates Reviewed: 04/2021, 07/2021, 08/2021, 10/2021, 08/2022, 08/2023, 05/2024

  1. Description of Procedure or Service

Amondys-45 (formerly SRP-4045) is an antisense oligonucleotide designed to bind to exon 45 of dystrophin pre-mRNA. This results in the exclusion or skipping of exon 45 which allows for production of dystrophin that is truncated, but still partially functional. It is estimated that approximately 8% of patients may be amenable to exon 45 skipping. Dystrophin is the protein that is absent in patients with Duchenne Muscular Dystrophy (DMD) which results in muscle damage and progressive dysfunction.

  1. Policy

Amondys-45™ (casimersen) is considered not medically necessary for all indications including treatment of Duchenne’s muscular dystrophy.

Note: There is insufficient clinical evidence for demonstrated efficacy.

  1. Key Points 1-6

Current treatment options for DMD focus on symptomatic management and prevention of complications. The mainstay of treatment is to offer patients glucocorticoids which have been confirmed to improve motor strength and function, pulmonary function, reduce the risk of scoliosis, and may delay the onset of cardiomyopathy. Current guidelines recommend initiation of glucocorticoids (such as prednisone) once patients reach a plateau of motor skill development, generally at age 4-6 years, but prior to onset of motor decline. Other therapies include ACE-inhibitors or Beta-blockers for cardiac disease, immunizations, pain management, respiratory support, and comorbidity surveillance. Eteplirsen was approved September of 2016 for the treatment of DMD in patients with a confirmed mutation of the DMD gene that is amenable to exon 51 skipping. Golodirsen and viltolarsen were approved (December 2019 and August 2020 respectively) for the treatment of DMD in patients with a confirmed mutation of the DMD gene that is amenable to exon 53 skipping.

In much the same way as the aforementioned exon-skipping therapies, casimersen approval occurred following priority review as an accelerated approval allowing for use of a surrogate endpoint (contingent upon verification of a clinical benefit in ongoing confirmatory clinical trials) of dystrophin increase in skeletal muscle observed in patients. Sarepta received FDA approval February 25, 2021. Whether the increase in truncated dystrophin level seen in the trial is reasonably likely to confer a clinical benefit remains to be elucidated. The below excerpts from the clinical study elaborate upon the question of clinical benefit posited with casimersen treatment.

  1. Clinical Trials and FDA Review 1-7

Study 1/ESSENCE/4045-301 (NCT02500381)

Patients in this Phase 3 trial were required to be ambulatory males between 7 and 13 years of age (median 9 years) on a stable dose of corticosteroids for at least 24 weeks with a mutation in the DMD gene amenable to exon 45 skipping. This is an ongoing, multicenter, two-part study. Part 1 is a double-blind, placebo-controlled 96-week treatment period which will be followed by a 48-week open-label treatment period (Part 2). Interim efficacy was assessed based on change from baseline in dystrophin biopsy at week 48 of Part 1. There were 43 evaluable patients (n=27 casimersen; n=16 placebo) assessed for dystrophin by Sarepta Western blot. The change from baseline mean were 0.22 and 0.81 for placebo and casimersen respectively which equates to a between group mean difference of 0.59 (p=0.004). The primary outcome measure is change from baseline in the total distance walked during 6MWT at Week 96 with an estimated primary completion date for the study of May 2022 (estimated study completion date May 2023).

  1. Billing Code/Availability Information

HCPCS Code:

  • J1426 – Injection, casimersen, 10 mg; 1 billable unit = 10 mg

NDC:

  • Amondys 45 100 mg/2 mL single-dose vial: 60923-0227-xx

  1. References
  1. Amondys 45 [package insert]. Cambridge, MA; Sarepta Therapeutics, Inc.; March 2023. Accessed March 2024.
  2. Topaloglu H, Gloss D, Moxley RT 3rd, et al. Practice guideline update summary: Corticosteroid treatment of Duchenne muscular dystrophy: Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2016 Jul 12;87(2):238.
  3. Bushby K, Finkel R, Birnkrant DJ, et al. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. Lancet Neurol; 2010 Jan; 9(1):77‑93.
  4. Bushby K, Finkel R, Birnkrant DJ, et al. Diagnosis and management of Duchenne muscular dystrophy, part 2: implementation of multidisciplinary care. Lancet Neurol; 2010 Jan; 9(2):177-189.
  5. Sarepta Therapeutics. A Double-Blind, Placebo-Controlled, Multi-Center Study With an Open-Label Extension to Evaluate the Efficacy and Safety of SRP-4045 and SRP-4053 in Patients With Duchenne Muscular Dystrophy. Available from: h https://clinicaltrials.gov/ct2/show/NCT02500381?term=NCT02500381&draw=2&rank=1. NLM identifier: NCT02500381. Accessed March 28, 2024.
  6. Darras BT, Urion DK, Ghosh PS. Dystrophinopathies. GeneReviews. www.ncbi.nlm.nih.gov/books/NBK1119/. Initial Posting: September 5, 2000; Last Revision: January 20, 2022. Accessed on March 28, 2024.
  7. Birnkrant DJ, Bushby K, Bann CM, et al. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management. Lancet Neurol 2018; 17:251.
  8. Birnkrant DJ, Bushby K, Bann CM, et al. Diagnosis and management of Duchenne muscular dystrophy, part 2: respiratory, cardiac, bone health, and orthopaedic management. Lancet Neurol 2018; 17:347.
  9. Moxley RT 3rd, Ashwal S, Pandya S, et al. Practice parameter: corticosteroid treatment of Duchenne dystrophy: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology. 2005;64:13–20.
  10. Gloss D, Moxley RT 3rd, Ashwal S, Oskoui M. Practice guideline update summary: Corticosteroid treatment of Duchenne muscular dystrophy: Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2016 Feb 2;86(5):465-72. Doi: 10.1212/WNL.0000000000002337. Reaffirmed on January 22, 2022.
  11. Childs, AM, Turner, C, Astin, R, et al. (2023). Development of respiratory care guidelines for Duchenne muscular dystrophy in the UK: key recommendations for clinical practice. thorax.
  12. Landfeldt, Erik. Measuring health-related quality of life in Duchenne muscular dystrophy: Current perspectives and recommendations. Journal of the Neurological Sciences 446 (2023).

Appendix 1 – Covered Diagnosis Codes

ICD-10

ICD-10 Description

G71.01

Duchenne or Becker muscular dystrophy

Appendix 2 – Centers for Medicare and Medicaid Services (CMS)

The preceding information is intended for non-Medicare coverage determinations. Medicare coverage for outpatient (Part B) drugs is outlined in the Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 Drugs and Biologicals. In addition, National Coverage Determinations (NCDs) and/or Local Coverage Determinations (LCDs) may exist and compliance with these policies is required where applicable. Local Coverage Articles (LCAs) may also exist for claims payment purposes or to clarify benefit eligibility under Part B for drugs which may be self-administered. The following link may be used to search for NCD, LCD, or LCA documents: https://www.cms.gov/medicare-coverage-database/search.aspx. Additional indications, including any preceding information, may be applied at the discretion of the health plan.

Medicare Part B Covered Diagnosis Codes (applicable to existing NCD/LCA/LCD): N/A

Medicare Part B Administrative Contractor (MAC) Jurisdictions

Jurisdiction

Applicable State/US Territory

Contractor

E (1)

CA, HI, NV, AS, GU, CNMI

Noridian Healthcare Solutions, LLC

F (2 & 3)

AK, WA, OR, ID, ND, SD, MT, WY, UT, AZ

Noridian Healthcare Solutions, LLC

5

KS, NE, IA, MO

Wisconsin Physicians Service Insurance Corp (WPS)

6

MN, WI, IL

National Government Services, Inc. (NGS)

H (4 & 7)

LA, AR, MS, TX, OK, CO, NM

Novitas Solutions, Inc.

8

MI, IN

Wisconsin Physicians Service Insurance Corp (WPS)

N (9)

FL, PR, VI

First Coast Service Options, Inc.

J (10)

TN, GA, AL

Palmetto GBA

M (11)

NC, SC, WV, VA (excluding below)

Palmetto GBA

L (12)

DE, MD, PA, NJ, DC (includes Arlington & Fairfax counties and the city of Alexandria in VA)

Novitas Solutions, Inc.

K (13 & 14)

NY, CT, MA, RI, VT, ME, NH

National Government Services, Inc. (NGS)

15

KY, OH

CGS Administrators, LLC