Drisapersen hype arrives and helps sink Sarepta

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For once in the back-and-forth battle over Duchenne muscular dystrophy projects it is drisapersen’s side that is hyping the data.

BioMarin Pharmaceutical is just days short of technically owning Prosensa and drisapersen, its exon-skipping asset, yet it appears to be under pressure to explain the $680m it is spending to acquire what is a phase III failure and big pharma reject. Thus chief executive Jean-Jacques Bienaime used the biggest biopharma investor forum of the year to present an unusually strident side-by-side comparison of drisapersen against its main rival, Sarepta’s eteplirsen, helping to amplify a steep decline in the latter company’s shares yesterday.

Shot itself in the foot

It did not help that Sarepta yesterday disclosed updated data from its phase II programme showing a continued decline in walking ability among patients who have been treated with eteplirsen for more than three years.

A 15% selloff on the basis of this data point would be a bit harsh, perhaps, as previous findings have hinted at only a slowing of disease progression rather than a complete reversal. However, it is consistent with the new narrative that drisapersen has the advantage.

In truth, drisapersen has a lot of explaining to do, too, which is why Mr Bienaime needed to use a significant amount of his time at the JP Morgan conference to justify the transaction. And to do that, it was probably necessary to call out a rival by name, against customary practice.

Mr Bienaime focused his DMD presentation on a cross-trial comparison of six-minute walk test data from both projects, stressing an average loss of 25 metres from baseline over 180 weeks for drisapersen, compared with an average loss of 107 metres at 144 weeks for eteplirsen. Prosensa’s analysis of drisapersen includes patients who lost walking ability altogether, and this comparison attempted to redress the balance by also including non-wakers in the Sarepta dataset.

Mr Bienaime's contention was that both sets of data needed to be censored in a similar fashion, something that had not been done until now. If non-ambulant patients are excluded from both, drisapersen shows a gain of 33 metres from baseline, versus a 32-metre loss for eteplirsen.

These are small numbers at this time point, however. In any case drisapersen failed to show a statistically significant benefit in this endpoint in the larger patient population and shorter time interval of a phase III trial, which is why it was no surprise that GlaxoSmithKline decided to pass (Other shoe drops on Prosensa as Glaxo hands back rights, January 13, 2014).

Nevertheless, Prosensa soldiered on and on the totality of the data has been allowed to make a rolling NDA submission with the FDA. Thus Prosensa was rewarded for its Dutch modesty; by contrast, Sarepta tried to short-circuit phase III and has been knocked back by the FDA (Sarepta’s credibility unravels, October 27, 2014). After years of hype, having no partnership and no opportunity to file has been a public embarrassment – Sarepta’s close of $11.91 yesterday is a 29-month low.

Raising the profile

BioMarin, of course, has been successful at putting rare disease drugs on the market, and perhaps Mr Bienaime believes that it has not been given enough credit for its business development efforts. Certainly, the market’s reaction to the Prosensa deal was not a spectacular endorsement – it generated a 2% rise on the day, and many analysts described the bet on drisapersen as “high-risk”.

His efforts this week seem to have worked. The presentation stimulated a 3% rise yesterday, and the stock is up another 3% this morning to a record $100 in early trading.

Whether this can be sustained is another matter, as Sarepta's chief executive, Chris Garabedian, is due to speak at JP Morgan on Thursday.

Given what Prosensa managed to accomplish in the clinic and with regulators, Mr Bienaime and BioMarin have bet on what appears to be the better candidate in this space. But many question marks hang over the supporting data, and if they have bought into a failed science then that hardly matters.

Trial ID
Eteplirsen phase II NCT01540409
Drisapersen phase III NCT01254019

To contact the writer of this story email Jonathan Gardner in London at jonathang@epvantage.com or follow @JonEPVantage on Twitter

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