Amylyx Pharmaceuticals, a Massachusetts-based drug developer, announced Wednesday it plans to ask U.S. regulators in the "coming months" to approve an experimental and closely watched treatment for ALS.
The decision is somewhat of a reversal, as Amylyx had said in April that the Food and Drug Administration wanted to see results from an additional, placebo-controlled clinical trial before reviewing the treatment. Executives told BioPharma Dive, though, that during a recent meeting the agency encouraged them to seek approval, a task Amylyx now intends to do while simultaneously running that new trial.
"It's hard to know exactly what the sort of change was, but it does in some ways feel like an evolution from the prior discussions," Justin Klee, one of Amylyx's co-founders, said in an interview.
Klee and fellow co-founder Josh Cohen couldn't say when exactly an approval application will be filed, but they believe it'll probably happen in less than six months. The company has already submitted its treatment, called AMX0035, to Canada's drug agency, and expects to do the same with European regulators by the end of this year.
"Patients with ALS have no time to wait," Cohen said, "so this is very much a nights and weekends — and all day, of course — project to try to shave days, hours, minutes off the timeline."
Wednesday's update is likely to go over well with patient advocacy groups like The ALS Association, which criticized the FDA for requesting more data on AMX0035 before a review.
Pushback from these groups escalated following the FDA's first-of-its-kind approval of Aduhelm, an Alzheimer's disease drug that has sparked controversy for several reasons, including a mixed track record in clinical testing.
ALS, short for amyotrophic lateral sclerosis and better known to some as Lou Gehrig's disease, is an illness characterized by a rapid and severe decline in cognitive and physical function. Once symptoms develop, the typical life expectancy for a patient with ALS is three to five years.
In the U.S., there are currently two FDA-approved medicines for ALS, both of which have limitations. Drug developers are trying to expand that list, but, as is true with many other neurological diseases, successes have been hard to find. Possible treatments from Brainstorm Cell Therapeutics, Cytokinetics and Alexion Pharmaceuticals have each failed important clinical tests over the last few years.
Amylyx's drug has therefore become a source of hope for patients and their caregivers. The medicine is a combination of the chemicals taurursodiol and sodium phenylbutyrate, the latter of which is used to treat a kind of inherited disease that impairs the body's ability to remove waste as it breaks down protein. Trial results so far have shown the two chemicals given together might help modestly slow ALS' course.
In a study of about 140 patients with rapidly progressing ALS, those who took AMX3005 declined slower than those who got a placebo. More detailed results, published a year ago in The New England Journal of Medicine, showed drug-treated patients scored on average 2.3 points higher on a scale that assesses how well they perform essential functions like breathing, speaking, walking and writing.
Further analysis later showed that patients who initially received the drug lived a median six and half months longer than those who didn't.
Though the results were deemed positive, patients given Amylyx's drug still declined.
The trial also raised questions. In an editorial published in NEJM, neurologists Michael Benatar and Michael McDermott noted how AMX0035 didn't do significantly better than placebo on secondary tests that measured hospitalization rates, muscle strength and other aspects of health.
The "lack of convincing supporting evidence" creates uncertainty around the drug's already "incremental" effect, Benatar and McDermott wrote.
Klee and Cohen know their drug won't stop ALS. But they believe the data generated thus far indicate it could be, at least for now, a valuable treatment option for patients who don't have many.
Notably, one of the ALS drugs available in the U.S., called Radicava, was approved in May 2017 based on data similar to some of what Amylyx has collected.
"This is certainly not a cure," Klee said. "But it is a first step. It's just as important that we keep figuring out: What's the next combination, and what's the next pathway we should target, and how do we further dive into the science?"
With results from the trial in hand, Amylyx approached regulators about marketing approval. Canada's drug regulator accepted the company's application in June, and a European filing is expected before the end of the year.
In the U.S., however, an approval looked further off.
The FDA initially responded to Amylyx by asking it to run another trial. The company subsequently decided to conduct a late-stage study that would take place in Europe and the U.S. and begin enrolling patients by the end September. Cohen said his team remains on track to dose the first participant by then, though "timing is tight."
The FDA's tune appears to have recently changed, however. Cohen said the agency encouraged Amylyx to submit an approval application during a July meeting. The company is now preparing to do that in parallel with the late-stage study, and has had follow-up conversations with the agency to "ensure the content and nature of the submission," according to Cohen.
"I think the FDA, if I had to take a guess, is very aware that these sorts of proposals are setting precedent," Klee said. "That's probably why they wanted to be very careful about how exactly we all go about it."