With the details from the DEMAND-III study, the full extent of the failure of Prosensa’s exon-skipping drug drisapersen to arrest progression of Duchenne Muscular Dystrophy (DMD) has become clear.

There are few grounds for optimism among the plethora of secondary end-points, no trends, not even a statistically significant post hoc sub-group analysis.  Only pages and pages of convincingly negative data.

While its obviously a relief that concerns about liver toxicities proved unfounded – the treatment was very safe – the safety profile is unlikely to be much consolation for such a convincing lack of efficacy.

But clear-cut as the data is, it leaves one very important question entirely unanswered: was the failure due to insufficient dystrophin production, or – more worryingly – because successfully elevating dystrophin is much less effective than has been assumed?

There are also lessons to be learned beyond DMD: the infinite subtlety of biology means that no phase 3 study is a “slam dunk” – failure lurks round every corner, even in the most unexpected of places.  Public market investors, in particular, can pump up asset valuations on an over-optimistic assessment of early clinical data (as the recent Intercept episode illustrates).  The chastening experience at Prosensa should serve as a warning that translating promise and potential into regulatory approval and sales is often more difficult than it first appears.

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RxCelerate Ltd is an outsourced drug development platform based near Cambridge, UK. We specialize in delivering an entire road map of drug development services from discovery and medicinal chemistry through to formal preclinical development and clinical up to Phase IIa. In the last five years, we have witnessed dramatic changes in the drug development …