As with many clinical trial results the devil is in the detail. Amicus Therapeutics' (NASDAQ:FOLD) attempts to add more detail to the results of its six-month phase III monotherapy trial for its Fabry disease drug Amigal appears not to have washed too well with investors.
Shares in the group took another pounding, falling by 26% to $2.89 on Friday as it announced that an analysis of secondary endpoints had also failed to meet statistical significance, following a previous miss with the primary endpoint. Even the prospect of a small subset of responders found through a re-analysis of data failed to turn the tide of sentiment, leaving Amicus with only the hope of some improvement in the 12-month data to reverse its fortunes.
If at first you don’t succeed
Amicus, however, should be admired for trying to snatch some kind of victory from the jaws of defeat after its shares crashed 44% last year on the news that the primary endpoint of reducing the build-up of the lipid substrate globotriaosylceramide (GL-3) from kidney interstitial capillaries of Fabry patients had been missed.
At that point there had been signs that the secondary endpoints of renal function and reduction of GL-3 in the urine might show promise. That little ray of hope was firmly extinguished last week at the Lysosomal Disease Network meeting, as management announced that these endpoints had also failed to meet statistical significance when compared to placebo.
Instead of focusing on failure, Amicus announced that patients with less than 0.3 interstitial inclusions per capillary in the kidney showed a highly significant response to treatment with Amigal, with reaction rates of 70% versus placebo.
While this imaginative slicing of the data could be admired, it has cut down what was already a very niche disease population further, with only 25 of patients in the 67-person study meeting the criteria. This means the drug could struggle to recover its development costs.
The other problem with the sub-group analysis is that this patient population was not predefined by the FDA when it set out the trial protocol for Amigal, meaning the agency might not accept it as part of a filing for the drug.
What might be on Amicus’s side is that, according to the company, the US regulator has agreed to consider the “entirety of data” from both the six- and 12-month studies of Amigal, rather than basing its decision on one single endpoint.
Consequently, Amicus’s fate is dependent on just how flexible the FDA is prepared to be. There is a slim chance that the paucity of alternatives might just swing it for Amigal. Fabrazyme is the only product approved in the US, and the Sanofi drug has issues with side effects and has to be infused.
As such, Amigal’s pill form and good safety track record will be trumpeted by Amicus management. There is also some historical precedent for the agency giving conditional approval – and that is all migalastat needs – for drugs addressing lysosomal storage disorders with mixed data.
Amicus is due to meet the FDA in the middle of this year and the outcome of those discussions should give a much clearer idea on the future direction of Amigal, as will the 12-month data, due at roughly the same time.
Amicus is hoping that treatment duration could have an impact on what have been, to date, very disappointing results. If the data again fail to come up to scratch the fate of Amigal as a monotherapy is almost certainly over. The drug’s last chance at redemption may well be as a combination product with Fabrazyme or Replagal.