Medical Policy

Policy Num:       99.001.001
Policy Name:    Gene Therapies for Duchenne Muscular Dystrophy
Policy ID:          [99.001.001] [Ac / L / M+ / P+ ] [5.01.46]

Last Review:       April 14, 2026
Next Review:       March 15, 2027

Publication Date: May, 2026
 

Related Policies: None

Gene Therapies for Duchenne Muscular Dystrophy

Summary

Description

Duchenne muscular dystrophy (DMD) is an inherited disorder that results in progressive muscle weakness and loss of muscle mass, primarily affecting males. DMD results from non-sense or frame-shifting variant(s) in the DMD gene, which is responsible for producing dystrophin, a cohesive protein essential for maintaining muscle support and strength. Delandistrogene moxeparvovec-rokl is an adeno-associated virus vector-based gene therapy which encodes a novel, engineered protein micro-dystrophin protein. This novel micro-dystrophin protein is a shortened version (138 kDa, compared to 427 kDa size of dystrophin expressed in normal muscle cells) that contains selected domains of dystrophin expressed in normal muscle cells.

Objective

The objective of this evidence review is to determine whether use of delandistrogene moxeparvovec-rokl improves the net health outcome in individuals with a confirmed diagnosis of DMD.

Policy Statements

The use of delandistrogene moxeparvovec-rokl is considered considered medically appropriate for individuals if they meet criteria 1 through 8 for the treatment of Duchenne muscular dystrophy.

Policy Guidelines

National P&T Approved Policy

Delandistrogene moxeparvovec-rokl

Delandistrogene moxeparvovec-rokl is considered medically appropriate for individuals if they meet criteria 1 through 8 :

1. At least 4 years of age at the time of infusion.

2. Assigned male at birth.

3. Diagnosis of Duchenne muscular dystrophy confirmed by documented variant in the DMD gene.

4. Documentation that there is not a deletion in exons 8 and/or 9 in the DMD gene.

5. Member is ambulatory and not wheelchair dependent – documentation from the medical record must be submitted

6. Anti-AAVrh74 total binding antibody titers are <1:400.

7. Physician attestation confirming no concomitant use of anti-sense oligonucleotides post-administration.

8. Individual does not have a history of receiving gene therapy or under consideration for treatment for another gene therapy for Duchenne muscular dystrophy.

Delandistrogene moxeparvovec-rokl is considered investigational when the above criteria are not met.

Delandistrogene moxeparvovec-rokl is considered investigational for all other indications.

Repeat treatment with delandistrogene moxeparvovec-rokl is considered investigational.

RECOMMENDED DOSE

The recommended dose is 1.33 × 10¹⁴ vector genomes (vg)/kg for individuals weighing 10 to 70 kg; the recommended maximum dose is 9.31 × 10¹⁵ vg for individual weighing 70 kg or greater.

Dosing Limits

1 injection per lifetime.

Other Considerations

In clinical trials, immune-mediated myositis has been observed approximately 1 month following an infusion of delandistrogene moxeparvovec-rokl in individuals with deletion mutations involving exon 8 and/or exon 9 in the DMD gene. Therefore, delandistrogene moxeparvovec-rokl is contraindicated in individuals with deletion mutations in exon 8 and/or exon 9. There is limited data for delandistrogene moxeparvovec-rokl in individuals with mutations in the DMD gene in exons 1 to 17 and/or exons 59 to 71. Individuals with deletions in these regions may also be at risk for a severe immune-mediated myositis reaction.

Coding

See the Codes table for details.

Benefit ApplicatioN

According to Circular Letter 24-0513- A (Amended) with the new initiatives of the government health plan where the Puerto Rico Health Insurance Administration (PRHIA) was implemented to include in the medical benefit Gene Therapy Medications and subject to medical necessity.  Therapies will include the product Elevidys (J1413).

Background

Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is an X-linked, recessive disorder that occurs in approximately 1 in every 3500 to 5000 males.^1, It primarily affects males. However, a females are also affected, but are usually asymptomatic. Even when symptomatic, most females typically only present with a mild form of the disease. According to U.S. epidemiologic data, the first signs or symptoms of DMD are noted at a mean age of 2.5 years (range, 0.2 to 1 years). Although histologic and laboratory evidence of myopathy may be present at birth, the clinical onset of skeletal muscle weakness usually does not become evident until early childhood. The average age at diagnosis is approximately 5 years.^2, Symptoms include motor difficulties such as difficulty running, jumping, and walking up stairs, along with an unusual waddling gait. Some improvement in symptoms may be seen from 3 to 6 years of age, though gradual deterioration resumes, and most individuals lose ambulation by age 12 and require noninvasive ventilation by the late teenage years. Individuals progress from needing noninvasive ventilation only during night sleeping, followed by noninvasive ventilation during day and night sleeping, and then noninvasive ventilation during day and night over the course of 5 to 10 years. Median life expectancy more recently has increased into the fourth decade, primarily through improved respiratory management and cardiac care.

DMD occurs as a result of variant(s) in the gene responsible for producing dystrophin, a cohesive protein that is essential for maintaining muscle support and strength. DMD is the longest known human gene, and several variants can cause DMD. Most deletion variants disrupt the translational reading frame in the dystrophin messenger RNA resulting in an unstable, nonfunctional dystrophin molecule. As a result, there is progressive muscle degeneration leading to loss of independent ambulation, as well as other complications, including respiratory and cardiac complications.^3, Genetic testing is required to determine the specific DMD gene variant(s) for a definitive diagnosis, even when the absence of dystrophin protein expression has been confirmed by muscle biopsy. There are over 4700 variants in the Leiden DMD mutation database, and the most common variants are concentrated between exons 45 and 53.

Regulatory Status

In June 2023, delandistrogene moxeparvovec-rokl (Elevidys; Sarepta Therapeutics) was approved by the U.S. Food and Drug Administration (FDA) for treatment of ambulatory pediatric patients aged 4 through 5 years with DMD with a confirmed mutation in the DMD gene. This indication was approved under accelerated approval based on expression of delandistrogene moxeparvovec-rokl micro-dystrophin in skeletal muscle observed in patients treated with delandistrogene moxeparvovec-rokl. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

In June 2024, the U.S. FDA expanded the approval of delandistrogene moxeparvovec-rokl (Elevidys; Sarepta Therapeutics) for ambulatory and non-ambulatory individuals 4 years of age and older with DMD with a confirmed mutation in the DMD gene. It received a traditional approval in ambulatory individuals 4 years of age and older with DMD with a confirmed mutation in the DMD gene, and accelerated approval in non-ambulatory individuals 4 years of age and older with DMD with a confirmed mutation in the DMD gene.

References

1. Bushby K, Finkel R, Birnkrant DJ, et al. Diagnosis and management of Duchenne muscular dystrophy, part 2: implementation of multidisciplinary care. Lancet Neurol. Feb 2010; 9(2): 177-89. PMID 19945914
2. Center for Disease Control and Prevention. Muscular Dystrophy: MD STARnet Data and Statistics. Available at http://www.cdc.gov/ncbddd/musculardystrophy/data.html. Accessed July 7, 2024.
3. Falzarano MS, Scotton C, Passarelli C, et al. Duchenne Muscular Dystrophy: From Diagnosis to Therapy. Molecules. Oct 07 2015; 20(10): 18168-84. PMID 26457695
4. Duchenne Muscular Dystrophy and Related Dystrophinopathies: Developing Drugs for Treatment Guidance for Industry. Published February 2018. Available at https://www.fda.gov/media/92233/download. Accessed July 7, 2024.
5. Zambon AA, Ayyar Gupta V, Ridout D, et al. Peak functional ability and age at loss of ambulation in Duchenne muscular dystrophy. Dev Med Child Neurol. Aug 2022; 64(8): 979-988. PMID 35385138
6. McDonald CM, Henricson EK, Abresch RT, et al. The 6-minute walk test and other endpoints in Duchenne muscular dystrophy: longitudinal natural history observations over 48 weeks from a multicenter study. Muscle Nerve. Sep 2013; 48(3): 343-56. PMID 23681930
7. Henricson E, Abresch R, Han JJ, et al. The 6-Minute Walk Test and Person-Reported Outcomes in Boys with Duchenne Muscular Dystrophy and Typically Developing Controls: Longitudinal Comparisons and Clinically-Meaningful Changes Over One Year. PLoS Curr. Jul 08 2013; 5. PMID 23867975
8. Food and Drug Administration. Statistical Reviewer: Thomas Zhou. STN: 125781/34. Available at https://www.fda.gov/media/179489/download?attachment. Accessed July 24, 2024.
9. Food and Drug Administration. Center Director Decisional Memo for BLA 125781//AMENDMENT 34; Elevidys (delandistrogene moxeparvovec-rokl). Available at https://www.fda.gov/media/179485/download. Accessed July 24, 2024.
10. Food and Drug Administration. Center Director Decisional Memo for BLA 125781; Elevidys (delandistrogene moxeparvovec-rokl). Available at https://www.fda.gov/media/169707/download. Accessed July 5, 2024.
11. Mendell JR, Sahenk Z, Lehman K, et al. Assessment of Systemic Delivery of rAAVrh74.MHCK7.micro-dystrophin in Children With Duchenne Muscular Dystrophy: A Nonrandomized Controlled Trial. JAMA Neurol. Sep 01 2020; 77(9): 1122-1131. PMID 32539076
12. Mendell JR, Sahenk Z, Lehman KJ, et al. Long-term safety and functional outcomes of delandistrogene moxeparvovec gene therapy in patients with Duchenne muscular dystrophy: A phase 1/2a nonrandomized trial. Muscle Nerve. Jan 2024; 69(1): 93-98. PMID 37577753
13. Mendell JR, Shieh PB, McDonald CM, et al. Expression of SRP-9001 dystrophin and stabilization of motor function up to 2 years post-treatment with delandistrogene moxeparvovec gene therapy in individuals with Duchenne muscular dystrophy. Front Cell Dev Biol. 2023; 11: 1167762. PMID 37497476
14. Zaidman CM, Proud CM, McDonald CM, et al. Delandistrogene Moxeparvovec Gene Therapy in Ambulatory Patients (Aged ≥4 to 8 Years) with Duchenne Muscular Dystrophy: 1-Year Interim Results from Study SRP-9001-103 (ENDEAVOR). Ann Neurol. Nov 2023; 94(5): 955-968. PMID 37539981
15. Prescribing Label: Elevidys (delandistrogene moxeparvovec-rokl) suspension, for intravenous infusion. Available at https://www.fda.gov/media/169679/download. Accessed on July 5, 2024.
16. Food and Drug Administration. Sponsor Briefing Document for SRP-9001 (delandistrogene moxeparvovec) for the treatment of duchenne muscular dystrophy. Cellular, Tissue, and Gene Therapies Advisory Committee. Meeting date 12 May 2023. Available at https://www.fda.gov/media/168022/download. Accessed July 12, 2024.
17. Gloss D, Moxley RT, Ashwal S, 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. Feb 02 2016; 86(5): 465-72. PMID 26833937
18. Feingold B, Mahle WT, Auerbach S, et al. Management of Cardiac Involvement Associated With Neuromuscular Diseases: A Scientific Statement From the American Heart Association. Circulation. Sep 26 2017; 136(13): e200-e231. PMID 28838934
19. 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. Mar 2018; 17(3): 251-267. PMID 29395989
20. 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. Apr 2018; 17(4): 347-361. PMID 29395990

Codes

Policy History