Sarepta Therapeutics announced positive results from its interim analysis of muscle biopsies at week 48, comparing casimersen treatment to placebo in the ESSENCE study, also known as study 4045-301. ESSENCE is a global, randomized double-blind, placebo-controlled Phase 3, 96-week study evaluating the efficacy and safety of casimersen and golodirsen in patients amenable to skipping exons 45 or 53, respectively.

Interim analysis found statistically significant increase in dystrophin production as measured by western blot in casimersen-treated participants compared to baseline and placebo. Based on these positive results, Sarepta intends to schedule a pre-NDA meeting with FDA and plans to submit an NDA for casimersen in the middle of 2019. We are hopeful that the ESSENCE study continues to yield positive results.

Read the Press Release from Sarepta

Sarepta Therapeutics Announces Positive Expression Results from the Casimersen (SRP-4045) Arm of the ESSENCE Study

— Interim analysis found statistically significant increase in dystrophin production as measured by western blot in casimersen-treated participants compared to baseline and placebo —

— Based on positive results, Company intends to schedule a pre-NDA meeting with FDA and plans to submit an NDA for casimersen in the middle of 2019 —

— Results once again validate the Company’s exon-skipping platform for the treatment of DMD —

CAMBRIDGE, Mass., March 28, 2019 (GLOBE NEWSWIRE) — Sarepta Therapeutics, Inc. (NASDAQ:SRPT), the leader in precision genetic medicine for rare diseases, today announced results from its interim analysis of muscle biopsy endpoints comparing casimersen treatment to placebo in the ESSENCE study, also known as study 4045-301. ESSENCE is a global, randomized double-blind, placebo-controlled Phase 3 study evaluating the efficacy and safety of casimersen and golodirsen in patients amenable to skipping exons 45 or 53, respectively.

After soliciting feedback from the FDA, Sarepta conducted an interim analysis for levels of dystrophin protein expression in those patients who are amenable to exon 45 skipping to determine the potential for a New Drug Application (NDA) filing based on dystrophin as a surrogate endpoint. With these results, the Company intends to work toward submission of an NDA for casimersen in the middle of 2019.

Patients amenable to exon 45 skipping were randomized to receive a once-weekly intravenous (IV) infusion of casimersen dosed at 30mg/kg (N=27) or placebo (N=16) for 96 weeks. The interim analysis was performed on data from biopsies of the bicep muscle at baseline and on-treatment at Week 48.

Key findings from the interim analysis include:

• In the casimersen arm, mean dystrophin protein (% normal dystrophin as measured by western blot) increased to 1.736% of normal compared to a mean baseline of 0.925% of normal (p<0.001).
• A statistically significant difference in the mean change from baseline to week 48 in dystrophin protein was observed between the casimersen-treated arm compared to the placebo arm (p=0.009).
• Of the 22 patients receiving casimersen who have been tested for increased exon-skipping mRNA using reverse transcription polymerase chain reaction (RT-PCR), all have displayed an increase in skipping exon 45 (p<0.001) over their baseline levels, representing a 100% response rate.
• A statistically significant positive correlation between exon 45 skipping and dystrophin production was observed (Spearman rank correlation = 0.635, p<0.001).
• The study is ongoing and remains blinded to collect additional efficacy and safety data.

“We are pleased to see that the anticipated exon skipping after treatment resulted in a statistically significant mean increase of dystrophin protein, as measured by western blot,” said Professor Francesco Muntoni, University College London. “This is the third exon-skipping agent to have shown a statistically significant increase in dystrophin production, and reinforces our confidence in the exon-skipping approach for treating Duchenne patients with amenable mutations.”

“The casimersen results and submission of our application for golodirsen earlier this year further validate our RNA research engine,” said Doug Ingram, Sarepta Therapeutics’ president and chief executive officer. “If golodirsen and casimersen are approved, nearly a third of the boys and young men living with DMD in the United States could benefit from our RNA therapies. We continue to advance toward our ultimate goal of profoundly improving the lives of as many patients around the world with DMD as possible.”

Dystrophin is a protein found in muscle cells that, while present in extremely small amounts (about 0.002 percent of total muscle protein), is crucial in strengthening and protecting muscle fibers. 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 of the body. The condition is universally fatal, and death usually occurs before the age of 30 generally due to respiratory or cardiac failure.

Casimersen uses Sarepta Therapeutics’ proprietary phosphorodiamidate morpholino oligomer (PMO) chemistry and exon-skipping technology to skip exon 45 of the DMD gene. Casimersen is designed to bind to exon 45 of dystrophin pre-mRNA, resulting in exclusion, or “skipping”, of this exon during mRNA processing in patients with genetic mutations that are amenable to exon 45 skipping. Exon skipping is intended to allow for production of an internally truncated dystrophin protein.

About the ESSENCE Study

The ESSENCE study is a double-blind, placebo-controlled, multi-center study to evaluate the efficacy and safety of casimersen (SRP-4045) and golodirsen (SRP-4053). Eligible patients with out-of-frame deletion mutations amenable to exon 45 or 53 skipping are randomized to receive once weekly intravenous (IV) infusions of 30 mg/kg SRP-4045 or 30 mg/kg SRP-4053 respectively (combined-active group) or placebo for up to 96 weeks. This is followed by an open label extension period in which all patients will receive open-label active treatment for 48 weeks, up to Week 144 of study.

Clinical efficacy is being assessed at regularly scheduled study visits, including functional tests such as the six-minute walk test (6MWT). All patients undergo a muscle biopsy at baseline and will undergo a second muscle biopsy either at Week 48 or Week 96.

Safety is being assessed through the collection of adverse events, laboratory tests, electrocardiograms (ECGs), echocardiograms (ECHOs), vital signs, and physical examinations throughout the study.

The study is titled, “A Double-Blind, Placebo-Controlled, Multi-Center Study With an Open-Label Extension to Evaluate the Efficacy and Safety of SRP-4045 and SRP-4053 in Patients With Duchenne Muscular Dystrophy.”

Read full press release.