Sarepta Therapeutics Announces Publication of Eteplirsen Clinical Study Results in the Annals of Neurology

Results Show a Significant Increase in Dystrophin Production and a Stabilization of Walking Ability in Duchenne Muscular Dystrophy Patients

CAMBRIDGE, MA--(Marketwired - Aug 8, 2013) - Sarepta Therapeutics, Inc. (NASDAQ: SRPT), a developer of innovative RNA-based therapeutics, today announced the first peer-reviewed publication of the 48-week results from the Phase IIb clinical study of eteplirsen in the Annals of Neurology. Eteplirsen is an investigational medicine in development for the treatment of patients with Duchenne muscular dystrophy (DMD) who have a genotype amenable to skipping of exon 51.

Published study results showed that once-weekly treatment with eteplirsen resulted in a statistically significant increase from baseline in novel dystrophin, the protein that is lacking in patients with DMD. In addition, eteplirsen-treated patients evaluable on the 6-minute walk test (6MWT) demonstrated stabilization in walking ability compared to a placebo/delayed-treatment cohort. Eteplirsen was well tolerated in the study with no clinically significant treatment-related adverse events. These data will form the basis of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for eteplirsen planned for the first half of 2014.

"These unprecedented data for eteplirsen in DMD patients with genetic mutations correctable by skipping exon 51 represent a significant milestone in the scientific community's efforts to address the tremendous need for treatments for this devastating and deadly disease in children," said Jerry Mendell, M.D., director of the Centers for Gene Therapy and Muscular Dystrophy at Nationwide Children's Hospital, principal investigator of the Phase IIb study and lead author of the publication. "For the first time in this disease, we have a potentially disease-modifying treatment that has demonstrated strong evidence of a relationship between a biochemical effect on dystrophin production and a clinically meaningful outcome on the 6-minute walk test. In addition, we believe this technology can potentially be applied to target additional genetic mutations in DMD in the future."

DMD is a rare degenerative neuromuscular disorder that causes progressive muscle loss, leading to severe disability and premature death. It 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 leads to loss of ambulation, limitations in activities of daily living, and serious cardiac and respiratory dysfunction. The condition is universally fatal, and patients typically die from complications of the disease in their twenties.

"The peer-reviewed publication of these data is an important achievement as we continue to advance eteplirsen through late-stage clinical development with the goal of bringing to patients and their treating physicians a safe and effective therapy that addresses the underlying cause of this devastating disease," said Edward Kaye, M.D., senior vice president and chief medical officer of Sarepta Therapeutics and a co-author of the publication. "The results published today provide the foundation of efficacy and safety data that we continue to build upon with our ongoing study of eteplirsen in DMD patients, with consistent results now seen through 84 weeks of treatment. We would like to thank all of the patients, families, physicians and healthcare providers who have diligently worked on the successful execution of this important clinical study of eteplirsen."

Summary of the Phase IIb Study and Key Results Through Week 48

The safety and efficacy of eteplirsen were evaluated in a 24-week randomized, double-blind, placebo-controlled study (Study 201). The study enrolled twelve boys aged seven to 13 years with a confirmed genotype amenable to treatment with an exon-51 skipping drug. These patients were randomized to one of three treatment arms including placebo (n=4), eteplirsen 30 mg/kg (n=4) and eteplirsen 50 mg/kg (n=4), and received eteplirsen or placebo weekly by intravenous infusion. After 24 weeks, all placebo-treated patients initiated weekly eteplirsen treatment at 30 mg/kg (n=2) or 50 mg/kg (n=2). After Week 28, all patients were rolled over into a long-term open-label extension study (Study 202), which continues to follow patients on clinical and safety measures with data reported through 84 weeks.

Dystrophin Production: The primary efficacy endpoint in Study 201 and Study 202 was the change from baseline in the percent of dystrophin-positive fibers present in muscle biopsies. Pre-treatment muscle biopsies were collected from all patients in the study. To evaluate the effect of eteplirsen dose and treatment duration on dystrophin production, a second biopsy was collected at week 12 from the four patients in the 50 mg/kg cohort and two placebo-treated patients, and at Week 24 from the four patients in the 30 mg/kg cohort and two placebo-treated patients. A third biopsy was collected in all patients at Week 48.

After 48 weeks of treatment, eteplirsen administered at either 30 mg/kg or 50 mg/kg for 48 weeks (n=8) resulted in a statistically significant increase (p 0.001) in dystrophin-positive fibers to 47.3 percent of normal. The placebo/delayed-treatment cohort, which had received 24 weeks of eteplirsen at either 30 mg/kg or 50 mg/kg following 24 weeks of placebo (n=4), also showed a statistically significant increase in dystrophin positive fibers to 37.7 percent of normal (p 0.008).

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Sarepta Therapeutics Announces Publication of Eteplirsen Clinical Study Results in the Annals of Neurology