The FDA has informed Sarepta Therapeutics that it will require additional time to complete its review of the new drug application (NDA) for eteplirsen for the treatment of Duchenne muscular dystrophy (DMD) amenable to exon 51 skipping. The Prescription Drug User Fee Act (PDUFA) date for eteplirsen has been extended to May 26, 2016. The rescheduled date for a meeting of the Peripheral and Central Nervous System Advisory Committee has not yet been determined.
The FDA notified Sarepta that its January 8, 2016, submission of four-year clinical efficacy data, which included additional six-minute walk test (6MWT) and loss of ambulation data compared with a historical control, has been designated as a major amendment to the NDA. The FDA stated that the PDUFA goal date has been extended by three months to allow a full review of the submission.
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. Eteplirsen uses 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.
DMD is an X-linked rare 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 boys worldwide. An 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. DMD is universally fatal, and death usually occurs before the age of 30.
Data from clinical studies of eteplirsen in DMD patients have demonstrated a consistent safety and tolerability profile and have also shown measurable dystrophin protein expression. Promoting the synthesis of a shorter dystrophin protein is intended to slow the decline of ambulation and mobility seen in DMD patients. No approved treatments for DMD are available in the U.S., and eteplirsen has not been approved by the FDA or any regulatory authority for this indication.
Source: Sarepta Therapeutics; February 8, 2016.