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Exon Skipping Drugs for Duchenne Muscular Dystrophy (DMD) (Eteplirsen (Exondys 51), Golodirsen (Vyondys 53), Viltolarsen (Viltepso)), Casimersen (Amondys 45)
08.01.34d

Policy

BENEFIT EXCLUSION

Exon-skipping drugs eteplirsen (Exondys 51), golodirsen (Vyondys 53), viltolarsen (Viltepso), and casimersen (Amondys 45)​ are a benefit contract exclusion for most plans, and, therefore, not eligible for reimbursement consideration. Individual benefits must be verified. ​

EXPERIMENTAL/INVESTIGATIONAL​

For plans that do not have an exon-skipping drugs (eteplirsen [Exondys 51], golodirsen [Vyondys 53], viltolarsen [Viltepso], or casimersen [Amondys 45]) benefit contract exclusion,​ these drugs are considered experimental/investigational and, therefore, not covered for treatment of Misspelled WordD​uchenne muscular dystrophy ​because their safety and/or effectiveness cannot be established by review of the available published peer-reviewed literature.

All other uses of exon-skipping drugs (eteplirsen [Exondys 51], golodirsen [Vyondys 53], viltolarsen [Viltepso], or casimersen [Amondys 45]) ​are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the Company medical policy on off-label coverage for prescription drugs and biologics.​


REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.​

Guidelines

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, eteplirsen (Exondys 51), golodirsen (Vyondys 53), viltolarsen (Viltepso), and casimersen (Amondys 45)​ are not eligible for payment under the medical benefits of the Company's products because they are considered experimental/investigational and, therefore, not covered.

Services that are experimental/investigational are a benefit contract exclusion for all products of the Company. Therefore, they are not eligible for reimbursement consideration.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

Eteplirsen (Exondys 51)


In September 2016, eteplirsen (Exondys 51; Sarepta Therapeutics) was approved by the FDA for treatment of individuals with Duchenne muscular dystrophy who have a confirmed variant of the Duchenne muscular dystrophy gene that is amenable to exon 51 skipping. This indication was approved under accelerated approval based on an increase in dystrophin in skeletal muscle observed in some patients treated with eteplirsen (Exondys 51).


The FDA, under the accelerated approval regulations (21 CFR 314.510), requires that Sarepta conduct a confirmatory trial to demonstrate the clinical benefit of eteplirsen (Exondys 51). In the preceding 3 years after the FDA approval, there has still been no publication of a trial confirming or refuting a clinical benefit of eteplirsen (Exondys 51). The European Medicines Agency rejected marketing approval for eteplirsen (Exondys 51) in September 2018.


Golodirsen (Vyondys 53​)


In December 2019, golodirsen (Vyondys 53; Sarepta Therapeutics) was approved by the FDA for treatment of individuals with Duchenne muscular dystrophy who have a confirmed variant of the Duchenne muscular dystrophy gene that is amenable to exon 53 skipping. This indication was approved under accelerated approval based on an increase in dystrophin in skeletal muscle observed in some patients treated with golodirsen (Vyondys 53).

The FDA, under the accelerated approval regulations (21 CFR 314.510), requires that Sarepta conduct a randomized, double-blind, placebo-controlled trial of 96 weeks with an open-label extension to 144 weeks to verify the clinical benefit of golodirsen (Vyondys 53​) with the primary endpoint of a 6-minute walk test. The expected date of trial completion is October 2025 and final report submission to the FDA by October 2025.


Viltolarsen (Viltepso)


In August 2020, viltolarsen (Viltepso) was approved by the FDA for the treatment of individuals with Duchenne muscular dystrophy who have a confirmed mutation of the Duchenne muscular dystrophy gene that is amenable to exon 53 skipping. This indication was approved under accelerated approval based on an increase in dystrophin production in skeletal muscle observed in patients treated with viltolarsen (Viltepso).

The FDA, under the accelerated approval regulations (21 CFR 314.510), requires that Nippon Shinyaku Co. conduct a randomized, double-blind, placebo-controll​ed trial over 48 weeks to verify the clinical benefit of viltolarsen (Viltepso) with the primary endpoint "time to stand." The expected date of trial completion is July 2024 and final report submission to the FDA by December 2024.


Casimersen (Amondys 45) 


In February 2021, casimersen (Amondys 45) was approved by the FDA for the treatment of individuals with Duchenne muscular dystrophy who have a confirmed mutation of the Duchenne muscular dystrophy gene that is amenable to exon 45 skipping. This indication was approved under accelerated approval based on an increase in dystrophin production in skeletal muscle observed in patients treated with casimersen (Amondys 45).

The FDA, under the accelerated approval regulations (21 CFR 314.510), requires that Sarepta verify the clinical benefit of casimersen (Amondys 45) by completing Study 4045­-301 (Essence), A Double-Blind, Placebo-Controlled, Multicenter Study with an Open-Label Extension to Evaluate the Efficacy and Safety of SRP-4045 and SRP-4053 in Patients with Duchenne Muscular Dystrophy. The study includes a randomized, double-blind, placebo-controlled period of 96 weeks and concludes after an open label extension period to 144 weeks. The primary endpoint will be the 6-minute walk test. The expected date of trial completion is October 2025 and final report submission to the FDA by October 2025.

Description

DUCHENNE MUSCULAR DYSTROPHY

Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder that occurs in approximately one in every 3500 to 5000 male individuals. A small number of girls are also affected, but they are usually asymptomatic, and even when symptomatic, only present with a mild form of the disease. According to United States epidemiologic data, the first signs or symptoms of DMD are noted at a mean age of 2.5 years (range, 0.2–1 years), and the mean age at definitive diagnosis is 4.9 years (range, 0.3–8.8 years). Symptoms include motor difficulties such as running, jumping, walking up stairs, and an unusual waddling gait. Some improvement in symptoms may be seen from 3 to 6 years of age, although gradual deterioration resumes and most individuals lose ambulation by age 12 and require noninvasive ventilation by 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.

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. Duchenne muscular dystrophy 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. Genetic testing is required to determine the specific Duchenne muscular dystrophy 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.

The current standard of pharmacotherapy is corticosteroids for all individuals regardless of genetic mutation. Treatment is initiated once individuals reach a plateau of motor skill development, generally at ages 4 to 6 years, but prior to onset of motor decline. The goal of corticosteroid therapy is to preserve ambulation and minimize respiratory, cardiac, and orthopedic complications.


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 dystrophin gene, which is responsible for producing dystrophin, a cohesive protein essential for maintaining muscle support and strength. Antisense oligonucleotides are short, synthetic, single-stranded oligodeoxynucleotides that selectively bind to specific exons of the dystrophin pre-messenger RNA, causing the exon to be skipped and thereby repairing the mutated reading frame resulting in production of an internally truncated, yet functional, dystrophin protein. Four antisense oligonucleotides—eteplirsen, golodirsen, viltolarsen, and casimersen—have been approved by the US Food and Drug Administration (FDA) for the treatment of DMD. Each targets a specific exon. For example, eteplirsen targets skipping of exon 51, golodirsen and viltolarsen target skipping of exon 53, and casimersen targets skipping of exon 45.


ETEPLIRSEN (EXONDYS 51)

Eteplirsen (Exondys 51) is an antisense oligonucleotide of the phosphorodiamidate morpholino oligomer (PMO) class that induces skipping of exon 51 and thereby repairing the mutated reading frame. The PMO class comprise stable RNA analogues that selectively bind to exon 51 of the dystrophin premessenger RNA. This causes the exon to be skipped and prevents that part of the code from being read during mRNA processing, thereby repairing the mutated reading frame in the mRNA coding sequence in individuals with a deletion in exons 45–50, 47–50, 48–50, 49–50, 50, 52, or 52–63 of this gene. As a result, eteplirsen (Exondys 51) enables the production of an internally truncated, yet functional, dystrophin protein.​

For individuals with a confirmed variant of the DMD gene that is amenable to exon 51 skipping who receive eteplirsen (Exondys 51), the evidence includes one randomized controlled trial (RCT), one ongoing prospective open-label trial with a concurrent untreated control arm, and multiple post-hoc studies with historical control. Relevant outcomes are disease-specific survival, change in disease status, functional outcomes, health status measures, quality of life, and treatment-related mortality and morbidity. For the single pivotal RCT, no formal sample size calculations were conducted. A sample size of 12 total individuals was selected with four individuals in three treatment groups. There was no statistically significant difference either in the mean change from baseline in the 6-minute walk test distance or change in the North Star Ambulatory Assessment total score between eteplirsen (Exondys 51)–treated individuals and placebo-treated individuals at week 48. While eteplirsen (Exondys 51) treatment resulted in dystrophin detection in muscle biopsy specimens, suggesting the production of (truncated) dystrophin, the amount of protein produced was very limited according to the Western blot results (0.44% of normal dystrophin at week 48 [Study 301]; 0.93% at week 180 [Study 201/202]). There are no satisfactory data clearly establishing the effectiveness of the truncated dystrophin. Further, the minimum beneficial amount of dystrophin expression to be translated into a clinical benefit has yet to be established. In the absence of clinical data convincingly demonstrating a clinical effect, it cannot be concluded that the amount of dystrophin expressed with eteplirsen (Exondys 51)​ will translate into a clinical benefit to individuals. Multiple analyses of long-term follow-up data from study 201/202 and 301 on functional outcome measures such as 6-minute walk test and pulmonary function suggest that the rate of decline in eteplirsen (Exondys 51)​–treated individuals was less as compared to historical controls. However, the post-hoc nature of the analysis and the fact that the cohorts were retrospectively identified within the untreated group of individuals is of serious concern (potential selection bias) and undermines the robustness of the data. Particularly, the 6-minute walk test is subject to inter- and intrasubject variability and is influenced by training and motivation, making it a less suitable outcome measure for external control group comparison. Thus the clinical benefit of treating DMD with eteplirsen (Exondys 51), including improved motor function and pulmonary function, has not been demonstrated. A confirmatory, prospective, and adequately powered trial is necessary to assess the net health benefit of eteplirsen (Exondys 51)​ in individuals with DMD amenable to 51 skipping. 

GOLODIRSEN (VYONDYS 53)

Golodirsen (Vyondys 53) is a phosphordiamidate morpholino oligomer engineered to treat those individuals with DMD who have genetic mutations subject to skipping exon 53 of the dystrophin gene.​

For individuals with a confirmed variant of the DMD gene that is amenable to exon 53 skipping who receive golodirsen (Vyondys 53), the evidence includes a two-part multicenter study comprising a part 1 (randomized, double-blind safety and tolerability study) and a part 2 (open-label efficacy and safety study). Relevant outcomes are disease-specific survival, change in disease status, functional outcomes, health status measures, quality of life, and treatment-related mortality and morbidity. Results of interim analysis were based on 25 individuals who received a weekly intravenous infusion of golodirsen 30 mg/kg. At week 48, the mean change in dystrophin protein levels was 0.924% increase from the baseline (1.019% vs. 0.095%; P<0.001). There are no satisfactory data clearly establishing the effectiveness of the truncated dystrophin. Further, the minimum beneficial amount of dystrophin expression to be translated into a clinical benefit has yet to be established. In the absence of clinical data convincingly demonstrating a clinical effect, it cannot be concluded that the amount of dystrophin expressed with golodirsen will translate into a clinical benefit to individuals. A confirmatory, prospective, and adequately powered trial is necessary to assess the net health benefit of golodirsen (Vyondys 53) in individuals with DMD amenable to 51 skipping.

VILTOLARSEN (VILTEPSO)

Viltolarsen (Viltepso) is the third DMD antisense oligonucleotide to be approved and the second specific for DMD individuals amenable to exon 53 skipping.

​
For individuals with a confirmed variant of the Duchenne muscular dystrophy gene that is amenable to exon 53 skipping who receive viltolarsen (Viltepso), the evidence includes a two-part multicenter study comprising a part 1 (randomized, double-blind safety and tolerability study) and a part 2 (open-label efficacy and safety study). Relevant outcomes are disease-specific survival, change in disease status, functional outcomes, health status measures, quality of life, and treatment-related mortality and morbidity. In eight individuals who received a weekly intravenous infusion of viltolarsen (Viltepso) 80 mg/kg, the mean increase in dystrophin protein levels from baseline was 5.3% (±4.5) of normal levels (P=0.01) at week 25. There are no satisfactory data clearly establishing the effectiveness of the truncated dystrophin. Further, the minimum beneficial amount of dystrophin expression to be translated into a clinical benefit has yet to be established. Outcomes derived from several timed function and muscle strength tests improved among individuals treated with viltolarsen (Viltepso) compared to a matched natural history control group. However, given the variability in the natural history of DMD, comparison to a natural history cohort has limited reliability. Further, the clinical relevance of the observed differences is unknown. In the absence of clinical data convincingly demonstrating a clinical effect, it cannot be concluded that the amount of dystrophin expressed with viltolarsen (Viltepso) will translate into a clinical benefit to individuals. A confirmatory, prospective, and adequately powered trial is necessary to assess the net health benefit of viltolarsen (Viltepso) in individuals with DMD amenable to 53 skipping. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.


CASIMERSEN (AMONDYS 45)​


Casimersen (Amondys 45) is an antisense oligonucleotide of the PMO subclass. PMOs are synthetic molecules in which the five-membered ribofuranosyl rings found in natural DNA and RNA are replaced by a six-membered morpholino ring. Each morpholino ring is linked through an uncharged phosphorodiamidate moiety rather than the negatively charged phosphate linkage that is present in natural DNA and RNA. Each phosphorodiamidate morpholino subunit contains one of the heterocyclic bases found in DNA (adenine, cytosine, guanine, or thymine). Casimersen (Amondys 45) is designed to bind to exon 45 of dystrophin pre-mRNA, resulting in exclusion of this exon during mRNA processing in individuals with genetic mutations that are amenable to exon 45 skipping. Approximately 8% of individuals with DMD have out-of-frame deletion mutations amenable to exon 45 skipping. Exon skipping is intended to allow for production of an internally truncated dystrophin protein.

 

Casimersen (Amondys 45) was approved by the FDA under accelerated approval based on an increase in dystrophin production in skeletal muscle observed in individuals treated with casimersen (Amondys 45). Continued approval may be contingent upon verification of a clinical benefit in confirmatory trials.

 

The Study of SRP-4045 (Casimersen) and SRP-4053 (Golodirsen) in Participants With Duchenne Muscular Dystrophy (ESSENCE) is an ongoing 96-week, Phase 3, double-blind, placebo-controlled, randomized clinical trial that will evaluate the efficacy of golodirsen (Vyondys 53) and casimersen (Amondys 45) in ambulatory individuals with DMD with out-of-frame deletion mutations amenable to skipping exon 53 and exon 45, respectively. The study will enroll 222 boys from 7 to 13 years of age, with genotypically confirmed DMD and 6-Minutes Walking Test (6MWT) greater than or equal to 300 meters and less than or equal to 450 meters. The primary endpoint is the change from baseline to Week 96 in 6MWT. Following the 96-week double-blind period, all individuals began or are to begin an additional 48-week open-label treatment period. Interim efficacy was assessed based on change from baseline in the dystrophin protein level (measured as percentage of the dystrophin level in healthy subjects, i.e., percentage of normal determined by Western Blot) at Week 48. Interim results from 43 evaluable individual​s (n = 27, casimersen (Amondys 45); n = 16, placebo) who had a muscle biopsy at Week 48 of the double-blind period have been reported. Individuals randomly assigned to casimersen (Amondys 45) had a baseline mean dystrophin level of 0.93% of normal. At week 48, the mean dystrophin level increased 0.81% to 1.74% of normal. Individuals randomly assigned to placebo had a baseline mean dystrophin level of 0.54% of normal. At week 48, the mean dystrophin level increased 0.22% to 1.15% of normal. A clinically meaningful change in level of dystrophin has not yet been established in humans. As such, the clinical significance of these results is not clear. Casimersen (Amondys 45) has not been studied in DMD that is not amenable to exon 45 skipping, nor in other forms of muscular dystrophy (e.g., Becker muscular dystrophy).


Inclusion criteria for the ESSENCE trial (NCT02500381) are found on clinicaltrials.gov and are listed as follows:

  • Male individuals aged between 7 and 13
  • Genotypically confirmed DMD, with genetic deletion amenable to exon 45 or exon 53 skipping
  • Stable dose of oral corticosteroids for at least 24 weeks
  • Intact right and left biceps or two alternative upper muscle groups
  • Mean 6MWT greater than or equal to 300 meters and less than or equal to 450 meters
  • Stable pulmonary function: forced vital capacity (FVC) equal to or greater than 50% predicted

The estimated primary completion date for ESSENCE is October 2025. An additional open label trial (NCT03532542) that requires individuals to have completed a clinical trial evaluating either casimersen (Amondys 45) or golodirsen (Vyondys 53), per protocol, was terminated in August 2023. Participants were either transitioned to a post-trial access program or another study, or declined further treatment.​ Currently, there are no published data or trial results available for casimersen (Amondys 45).​


For individuals with a confirmed variant of the Duchenne muscular dystrophy gene that is amenable to exon 45 skipping who receive casimersen (Amondys 45), the evidence includes a single double-blind, placebo-controlled phase 3 trial. An interim analysis conducted at week 48 with data for 46 individuals with exon 45 skipping (casimersen [Amondys 45]=27 and placebo=16) is available. Compared to those who received placebo, participants who received casimersen (Amondys 45) demonstrated a statistically significant increase in dystrophin production by 0.59% at week 48 as measured by Western blot. The mean change from baseline to week 48 in dystrophin production was 0.81% versus 0.22% (P=0.004) in the casimersen (Amondys 45) versus placebo arms, respectively. There are no satisfactory data clearly establishing the effectiveness of the truncated dystrophin. Further, the minimum beneficial amount of dystrophin expression to be translated into a clinical benefit has yet to be established. In the absence of clinical data convincingly demonstrating a clinical effect, it cannot be concluded that the amount of dystrophin expressed with casimersen (Amondys 45) will translate into a clinical benefit to individuals. A confirmatory, prospective, and adequately powered trial is necessary to assess the net health benefit of casimersen (Amondys 45) in individuals with DMD amenable to 45 skipping. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

References

Alfano LN, Charleston JS, Connolly AM, et al. Long-term treatment with eteplirsen in nonambulatory patients with Duchenne muscular dystrophy. Medicine (Baltimore). 2019;98(26):e15858.


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(4):347-361.

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(3):251-267.


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;9(1):77-93.


Bushby K, Finkel R, Birnkrant DJ, et al. Diagnosis and management of Duchenne muscular dystrophy, part 2: implementation of multidisciplinary care. Lancet Neurol. 2010;9(2):177-189.

Centers for Disease Control and Prevention. Muscular Dystrophy: MD STARnet Data and Statistics. 2016. http://www.cdc.gov/ncbddd/musculardystrophy/data.html. Accessed October 13, 2023.


Center for Drug Evaluation and Research. Application Number: 206488orig1s000. Summary Review. 2016; https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/206488_summary review_Redacted.pdf. Accessed October 13, 2023.


Center for Drug Evaluation and Research. Application Number: 212154Orig1s000. Summary Review. Available at https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212154Orig1s000SumR.pdf. Accessed on October 13, 2023.

Clemens PR, Rao VK, Connolly AM, et al. 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;77(8):982-991.

Committee for Medicinal Products for Human Use (CHMP) Assessment Report: Exondys. Published September 20, 2018, Available at https://www.ema.europa.eu/en/documents/assessment-report/exondys-epar-refusal-public-assessment-report_en.pdf. Accessed October 13, 2023.

Deflazacort, Eteplirsen, and Golodirsen for Duchenne Muscular Dystrophy: Effectiveness and Value. Institute for Clinical and Economic Review. https://icer.org/wp-content/uploads/2020/10/ICER_DMD-Final-Report_081519-2-1.pdf​​. Accessed October 13, 2023.

Duchenne Muscular Dystrophy and Related Dystrophinopathies: Developing Drugs for Treatment Guidance for Industry. Published February 2018. https://www.fda.gov/media/92233/download. Accessed October 13, 2023.


Falzarano MS, Scotton C, Passarelli C, et al. Duchenne Muscular Dystrophy: From Diagnosis to Therapy. Molecules. 2015;20(10):18168-84.

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. 2017;136(13):e200-e231.

Food and Drug Administration. FDA Briefing Document: Peripheral and Central Nervous System Drugs Advisory Committee Meeting, April 25, 2016. NDA 206488. Eteplirsen. 2016; https://www.fda.gov/media/97306/download. Accessed October 13, 2023.

Frank DE, Schnell FJ, Akana C, et al. Increased dystrophin production with golodirsen in patients with Duchenne muscular dystrophy. Neurology. 2020;94(21):e2270-e2282.

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. 2016;86(5):465-72.


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. 2013;5.


Kesselheim AS, Avorn J. Approving a Problematic Muscular Dystrophy Drug: Implications for FDA Policy. JAMA. 2016;316(22):2357-2358.

Khan N, Eliopoulos H, Han L, et al. Eteplirsen Treatment Attenuates Respiratory Decline in Ambulatory and Non-Ambulatory Patients with Duchenne Muscular Dystrophy. J Neuromuscul Dis. 2019;6(2):213-225.

Kinane TB, Mayer OH, Duda PW, et al. Long-Term Pulmonary Function in Duchenne Muscular Dystrophy: Comparison of Eteplirsen-Treated Patients to Natural History. J Neuromuscul Dis. 2018;5(1):47-58.

McDonald CM, Henricson EK, Abresch RT, et al. Long-term effects of glucocorticoids on function, quality of life, and survival in patients with Duchenne muscular dystrophy: a prospective cohort study. Lancet. 2018;391(10119):451-461.

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. 2013;48(3):343-356.

Mendell JR, Goemans N, Lowes LP, et al. Longitudinal effect of eteplirsen versus historical control on ambulation in Duchenne muscular dystrophy. Ann Neurol. 2016;79(2):257-271.

Mendell JR, Rodino-Klapac LR, Sa henk Z, et al. Eteplirsen for the treatment of Duchenne muscular dystrophy. Ann Neurol. 2013;74(5):637-647.

Prescribing label VILTEPSO (viltolarsen) injection, for intravenous use. Initial U.S. Approval: 2020. Available at https://www.viltepso.com/prescribing-information. Accessed October 13, 2023.


Prescribing Label: Amondys 45 (casimersen) injection, for intravenous use. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/213026lbl.pdf. Accessed on October 13, 2023.


Prescribing Label: VYONDYS 53 (golodirsen) injection, for intravenous use. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211970s000lbl.pdf. Accessed October 13, 2023.


Woodcock J, Dunn B. FDA Presentations for the April 25, 2016 Meeting of the Peripheral and Central Nervous System Drugs Advisory Committee. 2016. https://www.fda.gov/advisory-committees/peripheral-and-central-nervous-system-drugs-advisory-committee/slides-april-25-2016-meeting-peripheral-and-central-nervous-system-pcns-drugs-advisory-committee. Accessed October 13, 2023.

Coding

CPT Procedure Code Number(s)
N/A
ICD - 10 Procedure Code Number(s)
N/A
ICD - 10 Diagnosis Code Number(s)
N/A
HCPCS Level II Code Number(s)
J1426 Injection, casimersen, 10 mg

J1427 Injection, viltolarsen, 10 mg

J1428 Injection, eteplirsen, 10 mg

J1429 Injection, golodirsen, 10 mg​
Revenue Code Number(s)
N/A

Coding and Billing Requirements

Policy History

Revisions From 08.01.34d:​

01/01/2025
This version of the policy is effective 01/01/2025.

This version of the policy has been updated to communicate that the exon-skipping drugs eteplirsen (Exondys 51), golodirsen (Vyondys 53), viltolarsen (Viltepso), and casimersen (Amondys 45) are a benefit contract exclusion for most plans, and, therefore, are not eligible for reimbursement consideration. Individual benefits must be verified. 

For plans that do not have a benefit contract exclusion for exon-skipping drugs, including eteplirsen (Exondys 51), golodirsen (Vyondys 53), viltolarsen (Viltepso), and casimersen (Amondys ​ 45), these drugs are considered experimental/investigational and, therefore, not covered for treatment of Duchenne muscular dystrophy ​because their safety and/or effectiveness cannot be established by review of the available published peer-reviewed literature.​



Revisions From 08.01.34c:

​05/01/2024​
​This policy has been reissued in accordance with the Company's annual review process.​
​11/01/2023
​This policy has been reissued in accordance with the Company's annual review process​.​
​11/16/2022This policy has been reissued in accordance with the Company's annual review process​.​
​11/03/2021

​This policy has been reissued in accordance with the Company's annual review process. Description & Reference sections have been updated with minor changes to other sections as well.
​​10/01/2021
​This version of the policy is a result of code updates effective 10/01/2021.
 
The following procedure code was deleted: C9075 

The following procedure code was added: J1426

​

Revisions From​ 08.01.34b:

08/02/2021

This version of the policy is effective as of 07/19/2021, and is in place due to a policy update to communicate Casimerse (Amondys 45) is considered experimental/
investigational and, therefore, not covered for treatment of Duchenne muscular dystrophy and all other indications because its safety and/or effectiveness cannot be established by review of the available published peer-reviewed literature.


Revisions From​ 08.01.34a:

04/01/2021

This version of the policy is effective as of 04/01/2021, and is in place due to coding updates.

 

  • Procedure code C9071 was deleted from this policy.
  • Procedure code J1427 was added to this policy.​

Revisions From 08.01.34:
01/01/2021This policy is created to communicate Company's coverage position of experimental/investigational and, therefore, not covered​ for the uses of of exon skipping drugs (eteplirsen (Exondys 51), golodirsen (Vyondys 53), or viltolarsen (Viltepso)). ​

1/1/2025
1/1/2025
08.01.34
Medical Policy Bulletin
Commercial
No