The first treatment for Duchenne muscular dystrophy has been greenlighted by the Food and Drug Administration.

The injectable eteplirsen (Exondys 51) was approved under the accelerated approval pathway, designed to fast-track medicines thought to exceed the benefits of existing treatments for life-threatening diseases, and was also granted priority review and an orphan drug designation. Eteplirsen is specifically indicated for patients who have a confirmed mutation of the dystrophin gene predisposed to exon 51 skipping. This includes about 13% of the population with Duchenne muscular dystrophy, which occurs in about 1 of every 3,600 male infants worldwide.

“In rare diseases, new drug development is especially challenging due to the small numbers of people affected by each disease and the lack of medical understanding of many disorders,” Janet Woodcock, MD, the FDA’s director of the Center for Drug Evaluation and Research (CDER), said in a statement .

The FDA found that data submitted by Sarepta Therapeutics sufficiently demonstrated an increase in dystrophin production, raising the possibility that there may be clinical benefit in this patient cohort; however, because eteplirsen’s actual clinical benefit has not been established, the FDA is requiring Sarepta to conduct a clinical trial. The study will assess whether eteplirsen improves motor function of this patient population. If the trial fails, the FDA is likely to withdraw approval.

“Accelerated approval makes this drug available to patients based on initial data, but we eagerly await learning more about the efficacy of this drug through a confirmatory clinical trial,” Dr. Woodcock said.

The accelerated approval of eteplirsen is based on the surrogate endpoint of dystrophin increase in skeletal muscle observed in some patients given a trial of the drug. The drug’s tentative labeling shows that in a small, randomized trial, three of eight boys who received either 30 mg/kg or 50 mg/kg per week of eteplirsen experienced balance disorder and vomiting. Contact dermatitis also was reported in two of the boys treated with eteplirsen. None of these adverse reactions were reported in four boys who received placebo.

In subsequent studies of 88 boys given either 30 mg/kg or 50 mg/kg per week of eteplirsen for up to 208 weeks, adverse reactions were reported at rates of 10% or higher, including vomiting, contusion, excoriation, arthralgia, rash, catheter site pain, and upper respiratory tract infection.

Priority review status is granted to an investigational drug based on its potential to be a significant improvement in safety or effectiveness in the treatment of a serious condition. Orphan drug designation provides incentives such as clinical trial tax credits, user fee waiver, and eligibility for orphan drug exclusivity to assist and encourage the development of drugs for rare diseases.

In a letter to CDER staff, Dr. Woodcock said that “The approval of Exondys 51 reflects FDA’s ability to apply flexibility to address challenges we often see with rare, life-threatening diseases – while remaining within our statutory framework. In this case, flexibility is warranted because of the life-threatening nature of the disease; the lack of available therapy; the fact that the intended population is a small subset of an already rare disease; and the fact that this is a life-limiting disease of children. These factors, combined with the dystrophin production data – and the drug’s low risk profile – led the Agency to approve the drug under the accelerated approval pathway.”

Dr. Woodcock noted that in April 2016, members of an advisory committee recommended that there was not substantial evidence that the drug is effective in providing clinical benefit and also voted 7-6 against accelerated approval because of uncertainties about the dystrophin data presented by the sponsor. But Sarepta later submitted additional data showing substantial evidence of dystrophin production, although the amount of dystrophin produced was only a small fraction of the normal level, she said.

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