FDA Puts Off Muscular Dystrophy Drug Eteplirsen Decision

Advisors voted 7–3 against approval, but patient advocates clamor for a cure

The FDA has notified Sarepta Therapeutics that it is continuing its review and internal discussions related to the pending new drug application for eteplirsen, an investigational treatment for patients with Duchenne muscular dystrophy (DMD), and will not be able to complete its work by the Prescription Drug User Fee Act (PDUFA) goal date of May 26, 2016. The FDA has communicated that it will continue to work past the PDUFA goal date and will strive to complete its work “in as timely a manner as possible.”

The decision comes a month after an advisory panel voted 7–3, with three abstentions, that a clinical trial involving 12 patients did not provide sufficient evidence that the drug was effective for DMD patients with a specific genetic mutation. Meanwhile, patient advocates are pressuring the FDA to approve a treatment for the rare disease, which currently has no cure.

DMD is an X-linked degenerative neuromuscular disorder causing severe progressive muscle loss and premature death. One of the most common fatal genetic disorders, DMD affects approximately one in every 3,500 to 5,000 males worldwide. A devastating and incurable muscle-wasting disease, DMD is associated with specific errors in the gene that codes for dystrophin, a protein that plays a key structural role in muscle fiber function. Progressive muscle weakness in the lower limbs spreads to the arms, neck, and other areas. Eventually, increasing difficulty in breathing due to respiratory muscle dysfunction requires ventilation support, and cardiac dysfunction can lead to heart failure. The condition is universally fatal, and death usually occurs before the age of 30.

Eteplirsen is designed to address the underlying cause of DMD by restoring the dystrophin messenger RNA (mRNA) reading frame, thereby enabling the production of a shorter, functional form of the dystrophin protein. The drug uses a proprietary phosphorodiamidate morpholino oligomer (PMO) chemistry and exon-skipping technology to skip exon 51 of the dystrophin gene. Approximately 13% of the DMD population is amenable to exon 51 skipping. Promoting the synthesis of a shorter dystrophin protein is intended to slow the decline of ambulation and mobility seen in DMD patients.

Sources: Sarepta Therapeutics; May 25, 2016; and Reuters; May 25, 2016.