Last Review Date: 05/02/2024

Date of Origin: 09/01/2020

Dates Reviewed: 09/2020, 01/2021, 04/2021, 08/2021, 08/2022, 08/2023, 05/2024

1. Description of Procedure or Service

Viltolarsen (formerly NS-065/NCNP-01) is an antisense oligonucleotide designed to bind to exon 53 of dystrophin pre-mRNA. This results in the exclusion or skipping of exon 53 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 53 skipping. Dystrophin is the protein that is absent in patients with Duchenne Muscular Dystrophy (DMD) which results in muscle damage and progressive dysfunction.

2. Policy

Viltepso (viltolarsen) is considered not medically necessary for all indications including treatment of Duchenne’s muscular dystrophy.

Note: There is insufficient clinical evidence for demonstrated efficacy.

3. 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 was approved December of 2019 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, viltolarsen 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. NS Pharma received FDA approval August 12, 2020. 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 studies elaborate upon the question of clinical benefit posited with viltolarsen treatment.

4. Clinical Trials and FDA Review ^1-6

Study 1 (NCT02740972)

Patients in this Phase 2 trial were required to be ambulatory males between 4 and 10 years of age (median 7 years) on a stable dose of corticosteroids for at least three months with a mutation in the DMD gene amenable to exon 53 skipping. The initial 4-week period, assessing the safety of two doses of viltolarsen, was double-blind and placebo-controlled. Period 2 was a 20 week of open-label assessment of viltolarsen for safety and efficacy of either 40 mg/kg once weekly (N=8) or 80 mg/kg once weekly (N=8). Muscle biopsies were obtained from all patients at baseline and following 24 weeks of viltolarsen, then analyzed using Western blot normalized to myosin heavy chain (primary endpoint). Mean change in dystrophin levels, for those patient in the 80 mg/kg arm, increased from 0.6% (SD 0.8) of normal at baseline to 5.9% (SD 4.5) of normal by Week 25, with a mean change in dystrophin of 5.3% (SD 4.5) of normal levels (p=0.01).

RACER53 study (NCT04060199)

An ongoing, currently recruiting, double-blind, placebo-controlled, multi-center, Phase 3 study to evaluate the efficacy and safety of viltolarsen in ambulant boys between 4 to 7 years with DMD mutations amenable to exon 53 skipping. The study will enroll approximately 74 patients who will receive 80 mg/kg viltolarsen or placebo for up to 48 weeks. Clinical efficacy will be assessed regularly using functional tests (e.g., Time to Stand Test [TTSTAND]). The estimated primary completion date is November 2024.

5. Billing Code/Availability Information

HCPCS Code:

• J1427 – Injection, viltolarsen, 10 mg; 1 billable unit = 10 mg

NDC:

• Viltepso 250 mg/5 mL single-dose vial: 73292-0011-xx

6. References

1. Viltepso [package insert]. Paramus, NJ; NS Pharma, Inc.; January 2023. Accessed April 2024.
2. Topaloglu H, Gloss D, Moxley RT 3^rd, 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. Clemens PR, Rao VK, Connolly AM, et al; CINRG DNHS Investigators. Safety, Tolerability, and Efficacy of Viltolarsen in Boys With Duchenne Muscular Dystrophy Amenable to Exon 53 Skipping: A Phase 2 Randomized Clinical Trial. JAMA Neurol. 2020 May 26. doi: 10.1001/jamaneurol.2020.1264. Avail at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7251505/
6. Bushby K, Connor E. Clinical outcome measures for trials in Duchenne muscular dystrophy: report from International Working Group meetings. Clin Investig (Lond). 2011;1(9):1217-1235
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 3^rd, 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. 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 29, 2024.
12. 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.
13. 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

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