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Vyondys-53 (golodirsen)

Policy Number: PH-0520




Last Review Date: 08/04/2020

Date of Origin: 01/06/20

Dates Reviewed: 01/2020, 08/2020


FOR PEEHIP Members Only - Coverage excludes the provider-administered medication(s) outlined in this drug policy from being accessed through a specialty pharmacy. It must be obtained through buy and bill.
  1. Description of Procedure or Service

Golodirsen is an antisense oligonucleotide specifically indicated for the treatment of patients with DMD who have a confirmed mutation of the dystrophin gene that makes them more likely to respond to exon 53 skipping. Golodirsen’s intended mechanism of action is removal of exon 53 of the pre-messenger ribonucleic acid (RNA), thereby restoring the messenger RNA reading frame. This shift would enable the production of a truncated form of the dystrophin protein. By increasing the quantity of an abnormal, but potentially functional, dystrophin protein, the objective is to slow or prevent the progression of DMD.

  1. Policy

Vyondys-53 (golodirsen) 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

Duchenne muscular dystrophy (DMD), a form of muscular dystrophy, is a genetic disorder characterized by progressive muscle degeneration and weakness that predominantly affects males. It is the most common and severe form of muscular dystrophy among children and accounts for more than 50% of all cases. DMD is caused by a deficiency of dystrophin, a protein that helps strengthen muscle fibers and protect them from injury.

Prevalence in the United States is not exactly known but is estimated to be approximately 1.0-1.8 per 10,000 males age 5-24 years old. DMD appears typically in boys between ages 3 and 5 and progresses rapidly. Most people with DMD are unable to walk by age 12 and may later need a respirator to breathe. They usually die in their late teens or early 20s from heart trouble, respiratory complications, or infection.

Currently, there is no cure for DMD and therapies are supportive in nature. Physical therapy, occupational therapy, respiratory care, speech therapy, braces/wheelchairs/contractures and glucocorticoid therapy are among the many common therapies. Historically, glucocorticoids were the only pharmacologic treatment for DMD utilized to slow the progression of weakness.

  1. Clinical Trials and FDA Review

Golodirsen was approved through the FDA accelerated approval process.

“For purposes of accelerated approval, a surrogate endpoint is a marker, such as a laboratory measurement, radiographic image, physical sign, or other measure, that is thought to predict clinical benefit, but is not itself a measure of clinical benefit. Depending on the strength of the evidence supporting the ability of a marker to predict clinical benefit, the marker may be a surrogate endpoint that is known to predict clinical benefit (a validated surrogate endpoint that could be used for traditional approval), a surrogate endpoint that is reasonably likely to predict a drug’s intended clinical benefit (and that could therefore be used as a basis for accelerated approval), or a marker for which there is insufficient evidence to support reliance on the marker as either kind of surrogate endpoint (and that therefore cannot be used to support traditional or accelerated approval for a marketing application).”

Golodirsen (formerly SRP-4053) 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.

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.

In much the same way as eteplirsen, golodirsen 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. Initially, in August of 2019, the FDA voted against approval based on risk of infections related to intravenous infusion ports and renal toxicity seen in pre-clinical models of golodirsen and observed following administration of other antisense oligonucleotides. Sarepta appealed this decision and FDA approval was granted December 12, 2019. Whether the small 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 golodirsen treatment.

Taking these concerns regarding unconfirmed efficacy and clinical benefit into consideration, a pediatric neurologist specializing in the care of patients with Duchenne Muscular Dystrophy was consulted regarding the use of golodirsen. The expert opinion of this physician includes the following salient points: this drug will be offered to all patients with disease amenable to exon 53 skipping and there is currently no clinical efficacy data. This product would likely be initiated at an early age and continued indefinitely.

Study 4053-101 (NCT02310906)

Patients were required to have a mutation in the DMD gene amenable to exon 53 skipping. Part 1 was a double-blind, placebo-controlled, dose-titration study in 12 DMD patients randomized 2:1 to golodirsen, in four escalating dose levels, or placebo. Part 2 was a 168-week, open-label study at a dose of 30 mg/kg/week which included the 12 patients from Part 1 plus an additional 13 patients with DMD. Patients had a median age of 8 years and were on a stable dose of corticosteroids for at least 6 months. Muscle biopsies were obtained from all patients at baseline prior to treatment and at Week 48 of Part 2 and were analyzed using Western blot for dystrophin level (primary endpoint). Mean dystrophin levels increased from 0.095% (SD 0.07) of normal at baseline to 1.019% (SD 1.03) of normal by Week 48 of Study 1 Part 2, with a mean change in dystrophin of 0.924% (SD 1.01) of normal levels (p<0.001).

ESSENCE study (4045-301; NCT02500381)

An ongoing, currently recruiting, double-blind, placebo-controlled, multi-center, Phase 3 study to evaluate the efficacy of SRP-4045 and SRP-4053 for up to 96 weeks which will be followed by an open label extension period in which all patients will receive open-label active treatment for 48 weeks in patients with DMD amenable to skipping exon 45 and exon 53 respectively. Twice as many patients will receive active treatment as will receive placebo (2:1). Target estimated enrollment of 222 subjects, males aged 7-13 years. Clinical efficacy will be assessed via six-minute walk test. All patients will undergo a muscle biopsy at baseline and a second muscle biopsy either at Week 48 or Week 96. The estimated primary completion date is May 2023.


A Phase 3 open-label interventional extension study to evaluate the safety and tolerability of long-term treatment with casimersen or golodirsen in patients with DMD. Target estimated enrollment, by invitation, of 260 subjects (males between the ages of 7 to 23 years). The estimated primary completion date is August 2026

  1. Billing Code/Availability Information


  • J1429 – Injection, golodirsen, 10 mg


  • Vyondys-53 100 mg/2 mL single-dose vial: 60923-0465-xx
  1. References
  1. Vyondys 53 [package insert]. Cambridge, MA; Sarepta Therapeutics, Inc.; December 2019. Accessed June 2020.
  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. Kinane TB, Mayer OH, Duda PW, et al. Long-Term Pulmonary Function in Duchenne Muscular Dystrophy: Comparison of Eteplirsen-Treated Patients to Natural History. Journal of Neuromuscular Diseases 5 (2018) 47–58.
  6. Muntoni F, Frank D, Sardone V, et al. Golodirsen Induces Exon Skipping Leading to Sarcolemmal Dystrophin Expression in Duchenne Muscular Dystrophy Patients With Mutations Amenable to Exon 53 Skipping (S22.001). Neurology Apr 2018, 90 (15 Supplement) S22.001
  7. Institute for Clinical and Economic Review. Deflazacort, Eteplirsen, and Golodirsen for Duchenne Muscular Dystrophy: Effectiveness and Value. Final Evidence Report. August 15, 2019 Accessed December 2019.
  8. Khan N, Eliopoulos H, et al on behalf of the Eteplirsen Investigators and the CINRG DNHS Investigators. Eteplirsen Treatment Attenuates Respiratory Decline in Ambulatory and Non-Ambulatory Patients with Duchenne Muscular Dystrophy. J. Neuromuscular Dis, vol. 6, no. 2, pp. 213-225, 2019.
  9. Frank DE, Schnell FJ, Akana C, et al. Increased dystrophin production with golodirsen in patients with Duchenne muscular dystrophy. Neurology. 2020 May 26;94(21):e2270-e2282. doi: 10.1212/WNL.0000000000009233. Epub 2020 Mar 5



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