Sarepta Therapeutics, Inc., a developer of innovative RNA-targeted therapeutics, announced that the US Food and Drug Administration (FDA) has granted accelerated approval for Exondys 51 (eteplirsen) as a once weekly intravenous infusion of 30 milligrams per kilogram for the treatment of Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation in the DMD gene that is amenable to exon 51 skipping.

This indication is based on an increase in dystrophin in skeletal muscles observed in some patients treated with Exondys 51. A clinical benefit of Exondys 51 has not been established. Continued approval for this indication may be contingent upon verification of a clinical benefit in confirmatory trials. The most common adverse reactions compared to a placebo group were vomiting (38%) and balance disorder (38%) with contusion, excoriation, arthralgia, rash, catheter site pain, and upper respiratory tract infection also reported more frequently than placebo (= 10%).

“Today’s accelerated approval of Exondys 51 represents a major milestone in the treatment of Duchenne Muscular Dystrophy for patients amenable to skipping exon 51 by targeting the underlying genetic cause of the disease – the lack of the dystrophin protein,” said Edward Kaye, M.D., Sarepta’s interim chief executive officer and chief medical officer. “We are grateful to the many patients and investigators who participated in Exondys 51’s clinical studies. Exondys 51 represents the culmination of many years of work across our entire organization and the Duchenne community to address a critical unmet need by bringing this novel medicine to patients. We will continue to leverage what we have learned from Exondys 51 to facilitate future development of potential new treatments targeting additional exons with the goal of one day treating all DMD patients amenable to exon skipping.”

The underlying cause of Duchenne muscular dystrophy is a mutation or error in the gene for dystrophin, an essential protein involved in muscle fiber function. Certain genetic mutations in DMD involve the deletion of exons, which interrupt proper translation of the genetic code into protein.

Duchenne muscular dystrophy is a fatal genetic neuromuscular disorder affecting an estimated one in approximately every 3,500 – 5,000 males born worldwide. It is estimated that up to thirteen percent of people with DMD have mutations addressable by Exondys 51.

DMD is an X-linked rare degenerative neuromuscular disorder causing severe progressive muscle loss and premature death. DMD is estimated to affect approximately one in every 3,500-5000 males born 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.

Exondys 51 uses Sarepta’s proprietary phosphorodiamidate morpholino oligomer (PMO) chemistry and exon-skipping technology to skip exon 51 of the dystrophin gene. Exondys 51 is designed to bind to exon 51 of dystrophin pre-mRNA, resulting in exclusion of this exon during mRNA processing in patients with genetic mutations that are amenable to exon 51 skipping. Exon skipping is intended to allow for production of an internally truncated dystrophin protein. Data from clinical studies of Exondys 51 in a small number of DMD patients have demonstrated a consistent safety and tolerability profile. The pivotal trials were not designed to evaluate long-term safety and a clinical benefit of Exondys 51 has not been established.