Prosensa declares progress on drug target for Duchenne

Prosensa says it has developed a method of measuring a key protein in patients with Duchenne muscular dystrophy – which could be a major step towards proving the efficacy of its drug treatment.

The company, based in the Netherlands, is one of several firms developing treatments for Duchenne muscular dystrophy (DMD), the rare muscle wasting disease which strikes sufferers in their early teenage years, usually causing death by their early 20s.

Researchers in the field are becoming more optimistic, with regulators also acknowledging that more can be done to speed development of treatments for this currently incurable disease.

DMD is characterised by the absence or reduced levels of dystrophin, a protein which plays a key role in muscle health. Prosensa has six compounds in development targeted at DMD, including its lead product drisapersen, which aims to restore normal levels of dystrophin.

There are many technical barriers facing Prosensa, and until now, simply measuring levels of dystrophin in DMD patients was one of them.

But now the company says it has achieved a breakthrough in measuring the protein levels in patients with the condition, as well as those with the similar Becker's muscular dystrophy (BMD).

Prosensa says it has now developed an "accurate and reproducible" method for measuring dystrophin in patients. The company's semi-automated image analysis method has now been shown to be objective (operator independent), reproducible (in multiple samples and experiments) and sensitive for assessing dystrophin levels by immunofluorescence in muscle biopsies from BMD and DMD patients in natural history studies or clinical studies, using compounds aiming to restore dystrophin expression.

This method has also been tested as part of an international consortium initiative, the Biochemical Outcome Measures study group, which focuses on the optimisation of dystrophin assays.

"This innovative methodology, which has been developed by Prosensa, underscores our scientific commitment to understanding DMD and developing treatments for this devastating disease, said Dr. Giles Campion, Prosensa's chief medical officer and senior vice-president R&D.

He added that the company would share the developments with the scientific community, which should help support the DMD research field by enabling enhanced clinical trial protocols with more objective and representative measures of dystrophin.

But Campion added that challenges remain due to variability in the muscle, and said that no proof of a drug's efficacy could be established via in vitro methods.

"Clinical outcome measures, such as the six-minute walk test (6MWT), continue to be the optimal measurement of a drug's efficacy in DMD," he concluded.

FDA decision a turnaround in fortunes

The prospects for Prosensa and drisapersen looked bleak in January this year when GSK returned the rights to the drug following failure in Phase 3 trials.

Then in July, the FDA declared that the drug could after all be approvable, based on surrogate endpoints.

Other companies in the field include Sarepta Therapeutics and its drug eteplirsen, as well as PTC Therapeutics' and its candidate Translarna (ataluren). These companies have also experienced similar setbacks, but have both seen a reversal of fortunes, with Translarna receiving a positive opinion on its application for conditional marketing in Europe.