GlaxoSmithKline (GSK), one of the world’s leading research-based pharmaceutical and healthcare companies, and Prosensa, a Dutch biotechnology company, have reported that GSK’s phase III clinical study of drisapersen, an investigational anti-sense oligonucleotide, for the treatment of Duchenne Muscular Dystrophy (DMD) patients with an amenable mutation, did not meet the primary endpoint of a statistically significant improvement in the 6 Minute Walking Distance (6MWD) test compared to placebo.

A total of 186 boys were randomised to this double-blind, placebo-controlled study (DMD114044) and received drisapersen at a dose of 6mg/kg/week (N=125) or placebo (N=61) via subcutaneous injection over 48 weeks. The difference in 6MWD (mean (CI) 10.33m (-14.65, 35.31), p=0.415) between drisapersen and placebo groups did not reach statistical significance. There was no treatment difference in key secondary assessments of motor function: 10-meter walk/run test, 4-stair climb and North Star Ambulatory Assessment. The most commonly reported adverse events included injection site reactions (78 per cent for drisapersen vs 16 per cent for placebo) and renal adverse events (including subclinical proteinuria; 46 per cent for drisapersen vs 25 per cent for placebo). No patients had thrombocytopenia.

Full evaluation of the benefit-to-risk profile of drisapersen treatment across all studies is anticipated to be completed by year end. This may include analyses of pooled results from various drisapersen studies.

“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,” commented Carlo Russo, senior vice president, head of GSK Rare Diseases Research & Development. “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 programme 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 forthcoming scientific meetings and will also be published in a scientific peer-reviewed journal.

Drisapersen is not approved or licensed for use anywhere in the world.

Drisapersen, (previously GSK2402968/PRO051) an antisense oligonucleotide, which induces exon skipping of exon 51, is currently in late stage development for DMD.

GSK obtained an exclusive worldwide license to develop and commercialise drisapersen from Prosensa in 2009. Drisapersen has been designated orphan drug status in the EU, US and Japan. In June 2013, drisapersen was granted Breakthrough Therapy designation by the US Food and Drug Administration.

The overall clinical programme comprises three early phase studies (PRO051-01, PRO051-02 and DMD114673) and three double-blind, placebo-controlled studies (DMD114117, DMD114876 and DMD114044). Phase II results from DMD114117 were presented at Cold Spring Harbor in April 2013 and are posted on www.gsk-clinicalstudyregister.com. The phase II results of DMD114876 will be presented at DIA/FDA oligonucleotide meeting, Sept 25-27, 2013, Washington, USA and other scientific congress meetings this year.

The clinical programme also includes an open-label extension study DMD114349 for boys completing DMD114117 and DMD114044.

The dystrophin gene is the largest gene in the body, consisting of 79 exons. Exons are small sequences of genetic code which lead to the manufacture of sections of protein. In DMD, when certain exons are mutated/deleted, the RNA cannot read past the fault. This prevents the rest of the exons 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. This technology uses synthetic antisense oligonucleotides to skip an exon next to a deletion and thereby correct the reading frame, enabling the production of a novel dystrophin protein. Up to 13% of boys with DMD have dystrophin gene mutation/deletions amenable to an exon 51 skip.

GlaxoSmithKline – – is committed to improving the quality of human life by enabling people to do more, feel better and live longer.

Prosensa is engaged in the discovery and development of RNA-modulating therapeutics for the treatment of genetic disorders.