Amicus has been studying migalistat for close to a decade now and the majority of the patients that have had the opportunity to participate in the trials have elected to stay on the drug in the extension phases, some of them for more than 7 years. The reason is that Enzyme Replacement Therapy (ERT) requires IV infusions every 2-4 weeks and ERT is not a validated cure, so an oral therapy that could deliver similar efficacy as ERT would have a huge impact on this patient population. As pointed out in the most recent call, FOLD is looking to secure "accelerated/conditional" approval based on the impact of migalistat on renal function, just as Fabrazyme was approved in 2003 - Fabrazyme has never received full approval. It is clear that migalistat is a safe drug, given the median duration of patients in the Phase II extension trial have been on drug is over 5 years, so the issue is one of efficacy. Anybody that has listened to the call understands that the trial did not fail in proving efficacy, it simply proved how difficult it is to measure renal involvement/improvement in this disease for a good chunk of the patients. Take away the measurement noise for patients with baseline readings below 0.3, and it is clear there is a benefit here - the drug generated a greater than 50% reduction in GL3 in 60%+ of the patients treated at 6 months, consistent with earlier studies. If this percentage is maintained (or improved) at 12 months and if the placebo group patients generate a similar response rate after crossing over to treatment (there were 14 patients in the placebo arm that had GL3 levels above 0.3 and only two "responded" while on placebo), then this data will be sufficient to generate an accelerated approval. The FDA understands the clinical measurement issues associated with Fabry disease and how it impacts trial design and results, so anyone looking at the 6-month results and writing off this drug/trial as a failure just doesn't get it.
Concur with what you have written.
Also dont forget concurrent administration of Migalastat with their version of ERT is entering phase the clinic which I take to mean phase two/phase three trials last quarter this year/first quarter next year. These studies are pharmacologic measurement studies and are not looking at clinical but biochemical results like peak plasma values, tissue levels etc and will be over fairly quickly. Its possible that these will be approved and on the market by end of 2014 in colloboration with GSK.
The same holds for their Pompes coadministration studies.
Exactly - even if you doubt the monotherapy results with migalastat, the co-adminstration with ERT is a clear avenue to approval, just on the ability to reduce immune response issues, let alone improve efficacy. One interesting aspect of the accelerated approval process was revealed last week in a presentation that an FDA rep gave to an audience of DMD parents (if you have been following SRPT, Dr. Temple gave a webinar presentation through the Cure Duchenne website) and discussed how the FDA #$%$es treatments for rare diseases and how more and more they are relying on "patient reported outcomes" to #$%$ the efficacy of the drugs - i.e. how the drug has impacted their lives. With 16 patients from the Phase II trial that have been on migalastat for 5+ years, I'm sure they can find a patient or doctor to provide some solid anecdotal "evidence" of how this drug has performed.