Amicus saw its shares down by more than 20% this morning after news that its Fabry disease candidate migalastat did not meet the FDA’s requirements for a speedy review, and the biotech will also see any approval delayed until at least the end of the decade as it needs to create more data for the drug.
After its talks with the U.S. regulator, the company said in a statement that it will need to generate more data for any approval, specifically additional data on gastrointestinal (GI) symptoms in Fabry patients who have an amenable mutation.
The regulator also told the biotech that kidney globotriaosylceramide (GL-3) “is currently not considered a basis for an accelerated approval,” ending its hopes of a quick read-through.
John Crowley, chairman and CEO of Amicus Therapeutics, said: “While we believe that the totality of the data from our studies with migalastat support the submission of a new drug application today, we acknowledge the FDA's position that accelerated approval based on kidney GL-3 reduction is not currently an option.
“We have thus defined a plan to collect additional GI data to support full approval for migalastat that we believe is feasible in a reasonable amount of time and with a high likelihood of success based on positive GI data generated in our previous phase 3 Study 011. FDA has been flexible in allowing a crossover design and in our use of established GI endpoints to measure clinical benefit in Fabry patients. We are fully committed to the additional work necessary to move migalastat toward approval in the United States."
The new phase 3 study is set to begin next year, with data set for 2019, and will particularly focus on diarrhea. Analysts at Leerink said in a note to clients: “Recall, the earlier phase 3 study ('011) demonstrated stat. sig. improvements on diarrhea (p=0.03 over 6 mos.), which may bode well for success of this new endeavor depending on trial design specifics still to come.
“Although trial details are still scant (protocol still being finalized), mgmt. believes that a small (n~35), 12-mos., cross-over study design should suffice in combination with previous trial data to gain a full approval for migalastat in the U.S.”
The drug is in fact already approved in Europe, gaining an EMA nod in the spring under the name Galafold. The co had enjoyed until yesterday a billion-dollar market cap, but is now under $900 million.
But it has been beset with problem in the States, as the Cranbury, NJ-based biotech last year performed a surprising about-face maneuver at the FDA.
After first signaling to investors that a pre-NDA meeting with the agency had gone well, the biotech’s executive team did a careful read of the meeting notes, reviewed some follow-up communications and concluded that they had been seriously overconfident. This is where the prospect of a new trial (and thus a major delay) first came up.
It also saw a key trial fail back in 2012, which prompted GlaxoSmithKline to later drop out of its partnership with the co. Its path to approval appears to be getting no easier.
Fabry disease is a genetic lysosomal storage disease caused by an enzyme malfunction that allows a type of fat called globotriaosylceramide, GL-3, to accumulate in cells.
Despite being a rare disease, a number of meds are already on the market, including Sanofi/Genzyme’s Fabrazyme (agalsidase beta) and Shire's Replagal (agalsidase alfa).
Migalastat targets a range of mutations in the disease, making it potentially effective in 35% to 50% of the patient population. There are around 1,500 Fabry patients in the U.S., of whom around half show GI signs and symptoms, according to estimates from Leerink.