[Updated, 8/13/18, see below] The FDA has approved a new treatment for Fabry disease, a decision that represents the end of a winding, more than decade-long saga for the drug’s developer, Amicus Therapeutics. Its long journey also highlights how drug approval in the U.S. has changed just in the last two years, thanks to new FDA leadership and recent legislation that has put patient voices front and center.
The agency has approved migalastat (Galafold) for adult Fabry patients with a genetic variation responsible for to up to 50 percent of cases. Amicus (NASDAQ: [[ticker:FOLD]]) CEO John Crowley said the company will price the drug, a pill, below the average price, for adults, of the existing standard of care for Fabry patients in the U.S., which is an infusible treatment called agalsidase beta (Fabrazyme) from Sanofi. Amicus also pledges never to jack up the annual price of its drug higher than consumer inflation, he said.
[Updated with pricing details] On a conference call Monday morning, Crowley said migalastat’s list price is $315,000 per patient, per year. Amicus is comparing that price to the amount, $344,000, a very specific group of patients would pay per year for current therapies. Those patients are of the average weight (173 pounds) of those enrolled in Amicus’s clinical trials, Crowley said.
Crowley told Xconomy he decided not to adopt an outcomes-based pricing model, which ties the price of a drug to how well it works, because it would be “hard to implement in Fabry.” But doctors will still be able to quickly tell if patients are responding thanks to existing blood tests. And with those patients who do respond to the drug, the healthcare system will save annually on the costs associated with getting the agalsidase beta infusions at a hospital, he said.
People who have Fabry don’t properly clear out a certain type of fat from their cells, which can lead to kidney damage or heart attacks. It is typically treated with frequent infusions of a genetically engineered enzyme that replaces its missing or faulty counterpart. Migalastat, by comparison, is a small molecule meant to grab onto and stabilize the defective enzyme in Fabry.
Migalastat is approved in Europe, Canada, Australia, and Japan for Fabry patients with any one of 348 genetic mutations seen in up to half of those with the disease. But Amicus has spent more than a decade trying to get the drug, its first marketed product, approved in the U.S. (Xconomy profiled many of the twists and turns in this profile.)
After a big trial failure in 2012, Amicus tried to find better results retrospectively by digging through the data. The FDA was lukewarm to the idea, leaving Amicus with on-again, off-again ambitions for U.S. approval over the next few years.
In March 2015 Amicus said it aimed to seek a faster-than-usual, “accelerated” approval of migalastat in the U.S., based on data on migalastat’s impact on a biomarker—levels of a fatty substance, called GL-3, which builds up in the kidney cells of Fabry patients. Meanwhile, authorities in other countries were approving the drug, starting with European regulators in May 2016.
But the FDA shot down Amicus’s U.S. plans in November 2016, calling for Amicus to run another clinical trial to produce more long-term data on the often debilitating gastrointestinal symptoms Fabry patients have. Amicus initially estimated the study would take two to three years to enroll. But after more research, Crowley said enrolling Fabry patients who fit the trial’s strict criteria would have taken closer to five to seven years. “I just started to think this is not a practical study,” he said.
Unexpectedly, the FDA dropped those demands in July 2017, just a few months after Scott Gottlieb was sworn in as FDA commissioner. This about-face enabled Amicus to refile for approval without running another lengthy study.
Why did the agency change its mind just a year later? Such reversals are rare, but not unheard of. By rule, the FDA doesn’t explain why it rejects drugs or changes its decisions. In a statement at the time, the company said the reversal was based on “a series of discussions with and written communication received from the FDA.”
However, the Project on Government Oversight (POGO), a nonpartisan government watchdog, obtained a letter sent from Crowley to Gottlieb just days after Gottlieb was confirmed as the new FDA commissioner, asking the agency to reconsider its position. Gottlieb is a former venture partner at New Enterprise Associates, an Amicus investor. A POGO report in December 2017, which included a copy of the letter, suggested that the letter might have played a role in the FDA’s change of heart.
Crowley, for his part, waves off the report. “[POGO] tried to make much [ado] about nothing,” he contends. “To my knowledge,” Crowley says, the agency’s
