An antisense oligonucleotide being developed by GlaxoSmithKline and Prosensa as a treatment for Duchenne muscular dystrophy (DMD) is the latest drug to be awarded breakthrough therapy status by the FDA.
The compound – called drisapersen (formerly GSK2402968/PRO051) – is currently in late-stage development for the 13 per cent or so of boys with DMD who have mutations in the dystrophin gene that are suitable for treatment with the drug.
DMD is characterised by progressive destruction of muscle cells throughout life and affects one out of every 3,500 male births worldwide. The defect is caused by mutation of the dystrophin gene found on a specific region of the X chromosome known as exon 51.
Drisapersen is designed to induce ‘skipping’ of exon 51 when the dystrophin sequence on DNA is written to RNA. The resulting RNA sequences produce copies of dystrophin that – while shorter than the normal form of the protein – retain a lot more of their natural function and this reduces the rate of muscle cell destruction.
The FDA has deemed drisapersen a breakthrough therapy based on the results of a 53-patient phase II study reported in April which showed that boys taking drisapersen were able to walk 35 metres further than those on placebo, with the difference maintained up to 48 weeks.
Holland-based Prosensa and GSK are currently in a race with Sarepta Therapeutics of the US (formerly AVI BioPharma) to bring an exon 51-skipping drug for DMD to market, and the award of breakthrough status for drisapersen adds an edge to their rivalry.
Sarepta’s candidate – called eteplirsen – is in a 12-patient phase IIb trial that has reached 84 weeks’ duration, with the company reporting earlier this month that DMD patients treated with the drug maintained a benefit over placebo seen at 48 weeks.
The latest results showed that after 84 weeks patients on eteplirsen could walk 46 metres further than those on placebo. Some of the boys in the study are now 11 years old on average, an age when most would have lost the ability to walk.
Breakthrough status is designed to expedite the development and review of important new drugs for example by allowing approval with fewer patients in trials and establishing a higher level of dialogue between the sponsor and FDA.