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Prosensa announces Lancet Neurology publication of an exploratory phase II study (DEMAND II) demonstrating efficacy and safety of drisapersen in patients with Duchenne muscular dystrophy

Prosensa announces Lancet Neurology publication of an exploratory phase II study (DEMAND II) demonstrating efficacy and safety of drisapersen in patients with Duchenne muscular dystrophy

Leiden, The Netherlands – 8 September 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

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.

About Prosensa Holding N.V.
Prosensa (NASDAQ: RNA) is a biotechnology company engaged in the discovery and development of RNA-modulating therapeutics for the treatment of genetic disorders. Its primary focus is on rare neuromuscular and neurodegenerative disorders with a large unmet medical need, including Duchenne muscular dystrophy (DMD), myotonic dystrophy and Huntington’s disease.

Prosensa’s current portfolio includes six compounds for the treatment of DMD, all of which have received orphan drug status in the United States and the European Union. The compounds use an innovative technique called exon-skipping to provide a personalized medicine approach to treat different populations of DMD patients.

About DMD
Duchenne muscular dystrophy (DMD) is a severely debilitating childhood neuromuscular disease that affects up to 1 in 3,500 live male births. This rare disease is caused by mutations in the dystrophin gene, resulting in the absence or defect of the dystrophin protein. As a result, patients suffer from progressive loss of muscle strength, often rendering them wheelchair-bound before the age of 12. Respiratory and cardiac muscle can also be affected by the disease and most patients die in early adulthood due to respiratory and cardiac failure.

About exon skipping
The dystrophin gene is the largest gene in the body, consisting of 79 exons. Exons are small segments of genetic code which, via an intermediate step involving RNA, lead to the assembly of sections of protein. In DMD, when certain exons are mutated/deleted, the RNA cannot be processed past the fault. This prevents the remainder of the exons from being read, resulting in a non-functional dystrophin protein and the severe symptoms of DMD. RNA-based therapeutics, specifically antisense oligonucleotides inducing exon skipping, are currently in development for DMD. These antisense oligonucleotides skip an exon next to, or containing, the fault and thereby correct the RNA processing, enabling the production of a novel, largely functional dystrophin protein. Prosensa’s exon skipping technology was licensed from Leiden University Medical Center.

About drisapersen
Drisapersen induces exon 51 skipping in the dystrophin gene and is intended for up to approximately 13% of all DMD patients. Drisapersen has been granted orphan designation in the European Union and the United States and Breakthrough Therapy Designation in the United States.

The overall drisapersen clinical program comprises three double-blind, placebo-controlled studies (DEMAND II/DMD114117, DEMAND V/DMD114876 and DEMAND III/DMD114044) and two long term open-label extension studies (DMD114673 and DEMAND IV/DMD114349). To date, over 300 patients have participated in clinical studies of drisapersen at more than 50 trial sites in 25 countries.

About the DEMAND II study
DEMAND II was a phase 2, double-blind, exploratory, parallel group, placebo-controlled clinical study to assess two dosing regimens of drisapersen 6 mg/kg subcutaneously for efficacy, safety, and pharmacokinetics in patients with Duchenne muscular dystrophy. Thirteen specialist centres in nine countries (Australia, Belgium, France, Germany, Israel, Netherlands, Spain, Turkey, and UK) recruited patients aged 5 years or older with Duchenne muscular dystrophy, a confirmed drisapersen-correctable mutation in the DMD gene, could rise from the floor unaided in 7 s or less, had a 6-min walk distance (6MWD) of 75 m or more and had 6MWD within 20% of each other at the two screening visits and one baseline visit.  During a 3-week loading dose period patients received twice-weekly doses of drisapersen or placebo. After this period, patients received drisapersen 6 mg/kg or volume-matched placebo in either a continuous (once weekly after the first 3 weeks) or intermittent (twice weekly at weeks 1, 3, and 5; once weekly at weeks 2, 4, and 6; and no active drug in weeks 7–10 of each 10-week cycle) regimen for a total of 48 weeks. The primary endpoint was change from baseline in 6MWD at week 25.

About 6MWD
The 6MWD was chosen as the primary efficacy endpoint based on published validation work in subjects with DMD and on clinical observations that progression of disease can be estimated from this parameter. The 6MWD had successfully been used as a primary endpoint in registration studies of therapies designed to treat the underlying cause of disorders with neuromuscular and pulmonary manifestations such as Pompe’s disease, Hunter Syndrome, Morquio A Syndrome and pulmonary arterial hypertension

Forward Looking Statement
This press release contains certain forward-looking statements. All statements, other than statements of historical facts, contained in this press release, including statements regarding our strategy, future operations, future financial position, future revenues, projected costs, prospects, plans and objectives of management, are forward-looking statements. The words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “plan,” “predict,” “project,” “target,” “potential,” “will,” “would,” “could,” “should,” “continue,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Forward-looking statements in this press release include statements around our lead compound, drisapersen, and the regulatory review of this product candidate. Actual results may differ materially from those projected or implied in such forward-looking statements.  Such forward-looking information involves risks and uncertainties that could significantly affect expected results.  These risks and uncertainties are discussed in the Company’s SEC filings, including, but not limited to, the Company’s Form 6-K’s and the Company’s Annual Report on Form 20-F. In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. While we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so, even if our views change.

Issued for and on behalf of Prosensa by Instinctif Partners.

To contact the Prosensa team at Instinctif Partners, email

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Sue CharlesManaging Partner