What little remaining optimism that an immediate return might be made from the leading companies in Duchenne muscular dystrophy should have evaporated today with news that GlaxoSmithKline has handed back rights to Prosensa Holding's drisapersen. In just a matter of weeks, any belief that an RNA antisense candidate could hit the market at extraordinary speed has been brushed aside as big pharma has had a chance to review mid and late-stage data.
Prosensa’s loss of its partner was presaged by the failure of the phase III Demand 3 trial, although the Netherlands-based group remained hopeful that Glaxo would still see potential in the project or other pipeline assets (EP Vantage interview – Prosensa braces itself for Glaxo verdict, November 22, 2013). Prosensa has a richer pipeline of clinical-stage antisense candidates in muscular dystrophy than rival Sarepta Therapeutics, but there is no doubt now that much remains to be proven in this space.
This was confirmed by the fact that Glaxo handed back not just rights to drisapersen but also to the entire muscular dystrophy pipeline, which included the clinical candidates PRO044, PRO045 and PRO053. There is irony in the timing: it happened on the same day as Sanofi and Alnylam announced a big RNAi deal in rare diseases.
Leerink Partners analyst Joseph Schwartz wrote this morning that Glaxo’s decision suggested that pooling and subgroup analyses had not yielded any data that would allow for a regulatory filing. The hope was that looking at younger patients or pooling the data from Demand 3 with the phase II Demand 2 and 5 studies could yield a statistically significant effect on the six-minute walk time, the primary endpoint.
Glaxo’s decision to scrap its interest in the entire Prosensa programme is not necessarily surprising. All the projects use antisense, each one designed to skip a different exon or set of exons in the dystrophin gene depending on the deletion that has caused the defective production of the musculoskeletal protein.
The decision had a predictable effect on Prosensa’s US-listed shares, which sank 20% to $4.49. They remain marginally above the record low of $3.56 hit on November 4, however.
Mr Schwartz estimated that Prosensa ended 2013 with $98m in cash, allowing operations until mid to late 2015. A share price rebound by then would be helpful should the company need to raise more money, and data from follow-on compounds like PRO044 could begin to turn the business around.
Shares in Sarepta, meanwhile, were up 4% to $20.20 in early trading today. The antisense rival is some way off from reporting pivotal data for its project eteplirsen, and thus some optimism obviously remains that it will succeed where Prosensa has failed. Nevertheless, Prosensa’s news can do nothing to encourage talk that a partner or buyer will emerge for Sarepta soon.