Amylyx Pharmaceuticals has officially asked the Food and Drug Administration to approve its experimental and closely watched medicine for ALS.
Now, the FDA has around two months to decide whether Amylyx's application has all the necessary components. If so, the submission will be accepted and reviewed, a process which usually takes about 10 months before the agency issues a verdict.
That Amylyx is filing its medicine, known as AMX0035, this soon is a bit unexpected. Though it had collected some positive findings from a mid-stage clinical trial, the Cambridge, Massachusetts-based company said in April that the FDA wanted to see results from an additional, placebo-controlled study before initiating an approval review.
But the agency's stance has since changed. Amylyx executives recently told BioPharma Dive that, during a July meeting, FDA staff encouraged them to seek approval. The company is now doing that while planning a larger, late-stage study that should begin before the end of the year.
"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 during an interview in mid-September, when the company announced intentions to file for approval in the U.S. "in the coming months."
"I think the FDA, if I had to take a guess, is very aware that these sorts of proposals are setting precedent," Klee added. "That's probably why they wanted to be very careful about how exactly we all go about it."
ALS, short for amyotrophic lateral sclerosis and better known to some as Lou Gehrig's disease, is a progressive illness that destroys nerve cells. Over time, the disease causes muscles to weaken and lose function, making it increasingly difficult for patients to perform everyday activities like walking, speaking, eating and breathing.
Amylyx's application is based on a trial of close to 140 people who were diagnosed with ALS and had started showing symptoms within the past year and a half. The main goal was to see whether AMX0035 could slow functional decline associated with the disease better than a placebo. And on that measure, the drug succeeded.
Results published last year in the New England Journal of Medicine found that, over a 24-week period, patients given AMX0035 scored an average 2.3 points better than those on placebo, as measured by a 48-point scale that evaluates the severity of their disease. Further analysis also showed that participants who initially received Amylyx's drug lived a median of six and half months longer than those who didn't, with median survival at 25 months and 18.5 months, respectively, for the two groups.
"A 2- to 3-point change ... might sound small," Sabrina Paganoni, the trial's principal investigator, told BioPharma Dive at the time these data were being published. "But really, on this scale, even a small change can mean a large impact on daily life."
Amylyx hopes to put further support behind its drug with a trial named PHOENIX, which will include approximately 600 participants across roughly 65 sites in the U.S. and Europe, according to a company spokesperson.
The spokesperson added that, while too early to predict when exactly PHOENIX will wrap up, the trial will focus on two main measures for effectiveness: survival, and patients' scores on that 48-point scale over a period of 48 weeks. Secondary efficacy outcomes will include survival differences, changes in vital capacity and certain quality of life measures.
Amylyx has asked the FDA for a speedy review of its application, although the agency may still refuse to review the drug or choose to review it using a standard, rather than accelerated, pathway.
"Regardless of the review designation assigned to the application, we will work as quickly and efficiently as we can to ensure the FDA has everything it needs to make its decision," the company spokesperson wrote in an email.
Should AMX0035 pass muster with regulators, it would be the first new ALS treatment in the U.S. since the 2017 approval of Radicava, a drug developed by Mitsubishi Tanabe Pharma. Before Radicava, it had been more than two decades since the FDA cleared a novel ALS drug for market. Currently, the average life expectancy for ALS patients who demonstrate symptoms is three to five years.
Given the dire need for more treatment options, patient advocacy organizations have been putting greater pressure on the FDA to improve access to newly developed drugs. In April, for example, The ALS Association criticized the agency for its request for more data on AMX0035. The group's leader called out the FDA again in June, after it controversially approved Aduhelm, an Alzheimer's disease drug with a mixed track record in clinical testing.
Amylyx has already sought approval of AMX0035 in Canada, and expects to do the same in Europe by the end of the year.
Note: This story has been updated to clarify the status of discussions between Amylyx and the FDA.