Muscular dystrophy drug from GlaxoSmithKline, Prosensa fails PhIII

GlaxoSmithKline and Prosensa today conceded defeat in the Phase III study for drisapersen, one of two closely-watched therapies for Duchenne muscular dystrophy which had been vying for the lead in the field. Investigators reported that the therapy failed to significantly improve walking distance in patients.

"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," noted Carlo Russo, who heads up GSK's rare diseases research and development effort. "We are committed to evaluating the outcome of this study in the context of the overall development program 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."

Shares of Prosensa--a 2012 Fierce 15 company--are down 69% as of 12:19 p.m. EST ($RNA). The plunge slashed more than a half billion dollars in market value from the company in a matter of minutes.

DMD is a terrible inherited affliction that destroys the muscles and the lives of the boys it affects. Prosensa's exon-skipping technology, in-licensed by GlaxoSmithKline ($GSK), hoped to correct the genetic mutations that interfere with dystrophin expression, restoring an essential function that can delay and significantly correct the debilitating disease. And Prosensa has more than one program to consider; there are 6 that target various DMD populations.

Not everyone was willing to throw in the towel this morning, however. Leerink's Joseph Schwartz believes that pooled analysis of the drug data and another ongoing trial readout could salvage something from the wreckage.

"All eyes now turn to RNA/GSK's pre-specified pooled/covariate analysis, which could examine whether or not intervening variables such as age influenced the 6-minute-walk analysis," noted Schwartz. "We do not know the nature of such pre-specified analyses, so we'll be looking for more color on these tests on conference call this morning. RNA also has the ability to pool the DEMAND III data across studies, so if DEMAND V (expected in 4Q14) is successful, this could help the drisapersen/risk benefit argument, given the strong, statistically significant DEMAND II data. 

The news of the trial failure marks another big setback for GSK, which felt that drisapersen--recently named a "breakthrough therapy" by the FDA--was a top prospect in its late-stage pipeline. GSK also experienced a setback on the cancer vaccine MAGE-A3 recently. The pharma giant, though, has had a string of new drug approvals this year and won't be badly hurt by a single Phase III failure. But it's a disaster for the Dutch company Prosensa, which has been working on a slate of DMD programs. Prosensa went public recently, joining a batch of biotechs that have been scoring some big gains in the market.

The trial failure at GSK leaves Sarepta ($SRPT) as the clear leader in the field. While only watching results on a dozen boys in their early-stage study of eteplirsen, the efficacy and safety data have been very promising. Sarepta has been angling for an early approval of eteplirsen, and it's likely to gain even more support in the patient community with the eclipse of drisapersen. 

Sarepta's shares jumped quickly on the news and then immediately fell back, perhaps reflecting doubts about exon-skipping, an approach shared by the two companies.

- here's the press release

Special Report: Prosensa – 2012 Fierce 15