Leiden, The Netherlands, Sept. 8, 2014 (GLOBE NEWSWIRE) — LEIDEN, The Netherlands – September 8, 2014 – Prosensa Holding N.V. (NASDAQ: RNA), the biopharmaceutical company focusing on RNA-modulating therapeutics for rare diseases with high unmet need, today announced that the full data from its exploratory, double-blind, placebo-controlled Phase II study (DEMAND II/ DMD114117/ NCT01153932) of drisapersen in patients with Duchenne muscular dystrophy (DMD) have been published in Lancet Neurology http://bit.ly/1rSMpeJ.
The publication of the results of the study, which investigated the efficacy and safety of drisapersen given for 48 weeks, confirms the positive outcome of the DEMAND II study, which met its primary endpoint, with no reported major safety concerns.
Top line study results were first presented in April 2013. Drisapersen received Breakthrough Therapy designation in June 2013 from the FDA based upon this dataset. The DEMAND II study evaluated the effect of two different dosing regimens of drisapersen (continuous and intermittent) in 53 patients with DMD, at 13 specialist clinics in nine countries. At week 25 (primary endpoint), the mean 6-minute walk test distance (6MWD) had increased by 31•5m (SE 9•8) from baseline for continuous drisapersen, giving a mean difference in change from baseline of 35•1m (95% CI 7•59 to 62•60; p=0•014) versus placebo. This is the first time that a disease modifying therapy in DMD has shown a statistically significant and clinically meaningful treatment difference from placebo as measured by the 6MWD.
At week 49, the mean difference in 6MWD (35.9m) was clinically meaningful though no longer statistically significant (p=0.051). No statistically significant difference in 6MWD changes from baseline was observed between intermittent drisapersen and placebo at week 25 or 49, although analysis of the combined intermittent and continuous drisapersen treatment groups compared with combined placebo groups showed a significant difference in 6MWD at week 49 of 31m (95% CI 0•47 to 62•5, p=0•047). Most patients reported mild-to-moderate on-treatment adverse events; no adverse events led to withdrawal from the study.
Immunofluorescence showed increases in dystrophin protein expression in biopsies at week 25 compared with pre-treatment measures in both drisapersen groups, although no correlation with 6MWD was seen. A decrease in serum creatine kinase concentrations was seen for both drisapersen groups compared with placebosuggesting an improvement in the integrity of muscle fibers.
Lead author and principle investigator in the study, Professor Thomas Voit MD from the Institut de Myologie, Universite Pierre et Marie Curie, Paris, France said: “Publication of this key paper on drisapersen in one of the most esteemed peer-reviewed scientific journals in our field is a great endorsement of the robustness of the DEMAND II study and the clinical significance of the results. The DEMAND II study supports the efficacy of drisapersen in the context of the overall clinical program, and I am proud to be part of this important effort to deliver a much needed treatment option to DMD patients.”
Dr. Giles Campion, Prosensa’s Chief Medical Officer and co-author added “The DEMAND II study results are a positive indication that drisapersen can offer real hope as a DMD treatment as it showed a significant improvement in the primary endpoint in this group of DMD patients. These data will form an essential part of our regulatory submissions, which are currently in preparation.”
In June, Prosensa announced that the United States Food and Drug Administration (FDA) outlined a regulatory path forward for drisapersen, under an accelerated approval pathway, based upon existing data, including the DEMAND II study. Prosensa remains on track to pursuing regulatory filings for drisapersen, initially in the United States and Europe, with the FDA submission planned before the end of the year and an EMA submission shortly thereafter.
