FDA Grants Accelerated Approval to First Targeted Treatment for Rare Duchenne Muscular Dystrophy Mutation

The FDA has granted accelerated approval to golodirsen injection (Vyondys 53, Sarepta Therapeutics) to treat patients with Duchenne muscular dystrophy (DMD) who have confirmed mutation of the dystrophin gene that is amenable to exon 53 skipping.

DMD, a rare genetic disorder, is known as the most common type of muscular dystrophy. It is caused by an absence of dystrophin, a protein that helps keep muscle cells intact and leads to progressive muscle deterioration and weakness. The first symptoms usually manifest between 3 and 5 years of age and often occur in people without a known family history of the condition. The disorder primarily affects boys, occurring in approximately 1 in every 3600 male infants worldwide.

The approval is based on the surrogate endpoint of an increase in dystrophin production in the skeletal muscle observed in some patients treated with the drug. The data submitted by the applicant demonstrated an increase in dystrophin production that is reasonably likely to predict clinical benefit in patients with DMD who have a confirmed mutation, according to the FDA. However, a clinical benefit of golodirsen has not been established. The FDA considered the potential risks associated with the drug, the life-threatening and debilitating nature of the disease, and the lack of available therapy of golodirsen before making this decision.

The golodirsen injection was evaluated in a 2-part study. The first part included 12 patients with DMD, of whom 8 patients received the injection and 4 received the placebo. In the second part, the same 12 patients from the first part of the study were evaluated, with 13 additional patients who had not previously received the treatment.

The study found that dystrophin levels increased from 0.10% of normal at baseline to 1.02% of normal after 48 weeks of treatment with the drug or longer. The most common adverse effects reported by patients in the clinical studies were headache, fever, cough, vomiting, abdominal pain, cold symptoms, and nausea. In addition, hypersensitivity reactions, such as rash, fever, itching, hives, skin irritation, and skin peeling were reported by patients who were treated with the golodirsen injection.

The FDA is requiring the company to conduct a trial to confirm the drug’s clinical benefit as a part of the accelerated approval process. The ongoing study is designed to assess whether the golodirsen injection improves motor function of patients with DMD with a confirmed mutation of the dystrophin gene amenable to exon 53 skipping. The FDA may initiate proceedings to withdraw approval of the drug if the trial fails to verify clinical benefit.

Reference

FDA grants accelerated approval to first targeted treatment for rare Duchenne muscular dystrophy mutation [news release]. Silver Spring, MD; FDA: December 12, 2019. https://www.fda.gov/news-events/press-announcements/fda-grants-accelerated-approval-first-targeted-treatment-rare-duchenne-muscular-dystrophy-mutation. Accessed December 13, 2019.