Prosensa (RNA) has a lot of clinical data on its Duchenne muscular dystrophy drug drisapersen. That's good. Much of the drisapersen data are really inconsistent and come from negative clinical trials. That's bad.
The drisapersen phase II study known as "Demand V" is a good example of the quandary Prosensa is in. Demand V is a failed study. As first reported last fall, the DMD boys treated with a 6 mg/kg dose of drisapersen showed a 27-meter improvement in the six-minute walk test compared to placebo after 24 weeks of treatment, but the difference was not statistically significant.
Today, researchers are presenting an update from the Demand V study in which treatment with drisapersen and placebo was stopped at 24 weeks but the DMD boys were followed for another 24 weeks. The results are interesting: Boys originally treated with the 6 mg/kg dose of drisapersen remained stable, with a 27.9-meter improvement in the six-minute walk test over placebo. Like at 24 weeks, the difference in walking performance at 48 weeks was not statistically significant, however Prosensa and its researchers are calling the results "clinically meaningful" and "encouraging."
Prosensa shares are up 14% to $7.72 in Tuesday trading, although the stock is still down 68% from last fall when failed drisparsen studies were first announced.
This is what the Demand V study data look like at 24 weeks and 48 weeks. The chart comes from a poster being presented today a medical meeting:
The purple line represents the DMD boys treated with the 6 mg/kg dose of drisapersen, and as described, performance on the six-minute walk test stabilized during 24-week, post-treatment phase. The green line represents the DMD boys treated with a placebo, while the light purple line at the bottom are DMD boys treated with drisapersen at a 3 mg/kg dose. These boys fared worse than placebo. That's strange.
Also, look at overlapping error bars at all time points, which reflects both the statistical non-significance of these data and the difficulties drawing conclusions from a study with so few patients. [Yes, the same problem facing Sarepta Therapeutics (SRPT) and its DMD drug eteplirsen.]
Even if you're optimistic about the Demand V data, it's hard to reconcile these phase II results with the larger phase III study of drisapersen also presented last fall which showed DMD boys treated with 6 mg/kg of drisapersen losing the ability to walk almost from the beginning of the study. Drisapersen barely managed to outperform placebo.
Drisapersen's inconsistent performance from one study to the next is partially explained by differences in the baseline characteristics of the DMD boys enrolled. In the DEMAND V study presented today, the boys were generally healthier with higher baseline walking ability. We know that baseline walking ability is an important prognostic factor.
Prosensa also analyzed the DEMAND V study using a statistical model for "percent-predicted six-minute walk distance" which takes into account some of the patient variability inherent in studies of DMD patients (but not baseline six-minute walk.)
This is what those data look like. Consistent with the chart above.
Join the club, if you're struggling to figure out what all this means for drisapersen's future. Prosensa and GlaxoSmithKline (GSK) are still unraveling their partnership, which means Prosensa doesn't have full control over all the drisapersen data yet. Today's data presentation is indicative of what we'll probably see from Prosensa over the next months -- an attempt to rejigger or repurpose the inconsistent drisapersen data to find a coherent and persuasive story to bring in front of the FDA.
Prosensa has little choice right now. Glaxo ran big clinical trials of drisapersen and they failed. Glaxo then walked away. Before Prosensa invests in new drisapersen trials, the company might as well as try to get the drug approved based on the imperfect data in hand.