GlaxoSmithKline (GSK) and Prosensa suffered a setback when their antisense drug candidate for Duchenne muscular dystrophy (DMD) failed to show efficacy in a phase III trial.
The drug, called drisapersen, was unable to improve walking distances compared to placebo in the study, which involved 186 boys with a mutation in the dystrophin gene thought to be amenable to treatment with the antisense oligonucleotide.
After 48 weeks, boys who received drisapersen could walk approximately 10m further than those on placebo, but the difference was not statistically significant.
Earlier results from a phase IIb trial revealed a significant, 35-metre improvement on the 6MWT for drisapersen compared to placebo after 28 weeks' treatment and in June it was awarded breakthrough status by the US FDA.
Drisapersen is designed to induce 'skipping' of exon 51 when the dystrophin sequence on DNA is written to RNA, with the aim of producing a truncated but semi-functional form of the dystrophin protein that is abnormal in DMD, restoring some muscle function.
GSK and Prosensa's drug not only failed to improve scores on the six minute walking test (6MWT), the phase III study's primary endpoint, but was also unable to confer a benefit of secondary measurements of motor function, including the 10-meter walk/run test and four-stair climb.
"We appreciate that these results will be disappointing for boys with DMD and their families," said Carlo Russo, head of GSK's rare disease R&D unit.
UK medical charity the Multiple Dystrophy Campaign described the findings as a "heavy blow", although it pointed out that another exon-skipping approach for DMD - Sarepta Therapeutics' eteplirsen - remains in development.
"We await further news from the pharmaceutical firms involved on what their next steps with regard to drisapersen will be, when a full evaluation completes later this year," said the charity's chief executive Robert Meadowcroft.
Meanwhile, other approaches to DMD therapy apart from exon skipping include the use of the substitute protein utrophin, stem cell therapies and gene therapies, he added.