FDA Okays Eteplirsen (Exondys 51) for Duchenne Muscular Dystrophy

Megan Brooks

September 19, 2016

The US Food and Drug Administration (FDA) has granted accelerated approval to eteplirsen injection (Exondys 51, Sarepta Therapeutics), the first drug approved to treat patients with Duchenne muscular dystrophy (DMD).

Eteplirsen is specifically indicated for patients with a confirmed mutation of the dystrophin gene amenable to exon 51 skipping, which affects about 13% of the roughly 9000 to 12,000 people with DMD in the United States.

"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 that the company must conduct after approval," Janet Woodcock, MD, director of the FDA's Center for Drug Evaluation and Research, said in the statement.

The road to approval for eteplirsen has been rocky. In late April, as reported by Medscape Medical News, the FDA's Peripheral and Central Nervous System Drugs Advisory Committee concluded that studies of eteplirsen failed to provide persuasive evidence that the drug is effective in DMD.

But the vote was close. Three panel members felt that substantial evidence was provided to support eteplirsen as effective for treating DMD, compared with 7 who didn't and 3 who abstained. Some panel members acknowledged that the public speakers — 52 of them during the day-long proceedings — were compelling and that there is a profound unmet need for boys with DMD.

In late May, the FDA deferred a decision on eteplirsen.

DMD is a progressive, debilitating, and ultimately fatal inherited X-linked neuromuscular disease caused by mutations of the dystrophin gene that disrupts the mRNA reading frame, resulting in a lack of dystrophin. Eteplirsen was developed to cause "skipping" of exon 51 in mRNA, which could increase production of a truncated but partially functional dystrophin protein.

The accelerated approval of eteplirsen is based on the surrogate endpoint of dystrophin increase in skeletal muscle observed in some patients treated with the drug.

"The FDA has concluded that the data submitted by the applicant demonstrated an increase in dystrophin production that is reasonably likely to predict clinical benefit in some patients with DMD who have a confirmed mutation of the dystrophin gene amenable to exon 51 skipping," the agency said.

A clinical benefit of eteplirsen, including improved motor function, has not been established, and Sarepta Therapeutics is required to do a clinical trial to confirm the drug's clinical benefit.

Specifically, the trial will assess whether eteplirsen improves motor function of patients with DMD who have a confirmed mutation of the dystrophin gene amenable to exon 51 skipping. If the trial fails to verify clinical benefit, the FDA may initiate proceedings to withdraw approval of the drug, the agency said.

The most common side effects reported by patients taking eteplirsen in clinical trials to date were balance disorder and vomiting.

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