Duchenne Muscular Dystrophy Treatments in a State of Flux

Eteplirsen is an investigational medication produced by Sarepta Therapeutics for the treatment of Duchenne muscular dystrophy (DMD), one of the most common fatal genetic disorders and a devastating and incurable muscle wasting disease. Currently, there is no approved treatment in the United States for DMD.

Eteplirsen is designed to address the underlying cause of DMD by enabling production of a shorter, functional form of the dystrophin protein. Eteplirsen uses Sarepta’s proprietary exon-skipping technology to skip exon 51 of the dystrophin gene. Approximately 13% of the DMD population is amenable to exon 51 skipping. According to Sarepta, its data from clinical trials of eteplirsen in DMD patients showed a consistent safety and tolerability profile.

In April 2016, the FDA’s Peripheral and Central Nervous System Advisory Committee voted 6-7 against finding substantial evidence from adequate and well-controlled studies to show eteplirsen induces production of dystrophin to a level reasonably likely to predict clinical benefit. The committee also voted 3-7 (with 3 abstentions) against finding substantial evidence from the data in the study presented to show eteplirsen’s effectiveness for treatment of DMD.

Then, in late May 2016 the FDA notified Sarepta that its review and internal discussions relating to the pending New Drug Application for eteplirsen would not be completed by May 26, 2016, the date originally cited as the agency’s goal. However, the agency said it will continue to work past that date and strives to complete the work in a timely manner.

Another experimental drug for DMD from BioMarin Pharmaceutical, drisapersen (Kyndrisa), recently withdrew its European marketing application after discussions at the May 2016 meeting of the European Committee for Medicinal Products for Human Use indicated that a negative opinion would be issued for drisapersen. On May 31, 2016, BioMarin said it was discontinuing clinical and regulatory development of Kyndrisa as well as the 3 other first-generation follow-on products currently in phase 2 studies for distinct forms of DMD.

On June 2, 2016, Sarepta’s stock declined more than 25% on the news that the FDA had finalized and streamlined its expanded access (compassionate use) program for investigational drugs and biologics, widening access to investigational drugs for patients suffering from serious or immediately life-threatening diseases and for whom no comparable or satisfactory alternative therapy is available. Under the FDA’s program, drug manufacturers can charge for their direct manufacturing costs but they may not charge for administrative costs associated with providing their drug to patients whose physicians have requested that they receive the drug prior to FDA approval.