Duchenne Muscular Dystrophy Drug Fails in Phase 3

Susan Jeffrey

September 20, 2013

GlaxoSmithKline (GSK) and Prosensa today announced today that drisapersen, an investigational antisense oligonucleotide, failed to meet the primary endpoint in a phase 3 trial of statistical improvement in the 6-minute walking distance test vs placebo in Duchenne muscular dystrophy (DMD) patients with a mutation thought amenable to the treatment.

Drisapersen induces exon skipping of exon 51 and is in late-stage clinical investigation for DMD. It has been designated orphan drug status in Europe, the United States, and Japan and in June 2013 was granted Breakthrough Therapy designation by the US Food and Drug Administration.

In this phase 3, double-blind trial, called DMD114044, 186 boys with DMD were randomly assigned to receive drisapersen at a dose of 6 mg/kg/week (n = 125) or placebo (n = 61) by subcutaneous injection during a 48-week period. The mean difference between the groups on the 6-minute walking distance test was a mean of 10.33 meters (confidence interval, -14.65 to 35.31; P = .415), which was not statistically significant.

Nor was there any treatment difference seen in secondary endpoints, including the 10-meter walk/run test, the 4-stair climb, and the North Star Ambulatory Assessment.

The most commonly reported adverse events with drisapersen vs placebo were injection site reactions (78% vs 16%) and renal adverse events (including subclinical proteinuria, 46% vs 25%). There were no cases of thrombocytopenia, the companies note.

GSK obtained an exclusive worldwide license to develop and commercialize this drug from Prosensa in 2009.

"We appreciate that these results will be disappointing for boys with DMD and their families. We would like to sincerely thank all those who participated in the study for their commitment," Carlo Russo, senior vice president and head of GSK Rare Diseases Research and Development, commented in the press release. "We are committed to evaluating the outcome of this study in the context of the overall development programme with experts in the field, and we expect such evaluation to help inform our next steps for drisapersen. It is our hope that progress will be made in an effort to help boys with DMD."

"While we are disappointed that this study did not meet its primary endpoint, we remain committed to the overall program and will continue to work closely with GSK," said Hans Schikan, chief executive officer of Prosensa. "With no long-term disease-modifying therapies available for DMD patients, research and development of possible treatment options is of critical importance for boys and their families affected by this debilitating disease."

Results have been submitted for presentation at upcoming scientific meetings and will also be submitted for publication in a scientific peer-reviewed journal, the companies' statement adds. "Full evaluation of the benefit-to-risk profile of drisapersen treatment across all studies is anticipated to be completed by year end," it notes, and may include analyses of pooled results from various drisapersen studies.

The clinical development program includes 3 early-phase studies (PRO051-01, PRO051-02, and DMD114673) and 3 double-blind, placebo-controlled studies, including the one reported today (DMD114117, DMD114876, and DMD114044).

Phase 2 results from DMD114117 were presented in April and are posted at the GSK site. A second phase 2 study, DMD114876, will be presented at DIA/FDA oligonucleotide meeting, 25-27 Sept 2013, Washington, DC, and other scientific congress meetings this year, the statement adds. There is also an open-label extension study, DMD114349, for patients completing DMD114117 and DMD114044.

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