Like many diseases of the brain, ALS continues to be an elusive target for drug developers. Promising therapies have failed time and again, putting added pressure on the next potential treatment to succeed. Currently, just two medicines are used to combat the disease, and both have their limitations.
Among the new drugs in development, one of the most closely watched comes from Amylyx Pharmaceuticals, a Cambridge, Massachusetts-based company. Last year, results from a small study showed patients treated with Amylyx's drug, known as AMX0035, appeared to do modestly better at performing essential functions like speaking, walking and writing compared to those who got a placebo. The study also found patients had slower functional declines and lived longer after receiving AMX0035.
With those results in hand, Amylyx concluded it had enough evidence to ask for approval. In March, the company said it would file a marketing application to Canada's drug regulator, Health Canada, during the first half of this year. And on Wednesday, it announced plans to do the same with European agencies by the end of 2021.
But in the U.S., the regulatory timeline could be considerably longer, as Amylyx also just revealed the Food and Drug Administration wants to see data from an additional placebo-controlled study before the biotech can submit AMX0035 for approval. To meet that request, Amylyx intends to run a late-stage clinical trial in Europe and the U.S., with enrollment expected to begin sometime between July and September.
Amylyx leaders said they'll work with the FDA to meet these data needs as quickly as possible. Still, Wednesday's announcement raises further questions around what's become an unusual regulatory case.
Often, the FDA is the first stop for drug companies looking to get their treatments on the market. That's especially true when the company is based in the U.S. or runs part of its clinical programs there. Yet with AMX0035, Amylyx will file in Canada and Europe well before getting to a stateside application.
"What I would say with Health Canada is that they moved really quickly with us," Josh Cohen, Amylyx's co-founder and co-CEO, said in a March interview with BioPharma Dive. "Frankly, I think the FDA is at that point now. But it took them a little bit to sort of come around."
To patient groups like The ALS Association, the hold-up in the U.S. is reflective of larger problems at the FDA. In a statement, the association called out the agency for not following its own guidance on drug approvals, and for not trying to bring forth new ALS treatments as urgently as its counterparts.
"Americans living with ALS deserve the same access to potentially beneficial treatments that Canadians and Europeans soon will likely have," Calaneet Balas, president and CEO of The ALS Association, said in the Wednesday statement. "We have asked the FDA to approve AMX0035 as soon as possible. So far, those calls have been ignored."
Notably, the FDA's stance on AMX0035 comes shortly after another experimental drug for ALS drummed up controversy.
Late last year, a New York biotech called Brainstorm Cell Therapeutics disclosed that its stem cell-based ALS therapy did not meet the main goal of a late-stage trial. Despite the failure, Brainstorm's CEO Chaim Lebovitz said he was confident there was a path forward for the therapy.
By February, though, approval prospects seemed dim. Brainstorm said it had heard back from the FDA, and the agency did not believe there was enough evidence to support a marketing application.
That announcement was also met with strong rebukes from patient groups and advocates, who admonished the FDA for not recognizing the dire need for new ALS therapies. Brainstorm could still submit its treatment without additional data, though the odds of approval are likely slim after the FDA's feedback.
Following these criticisms, the FDA took the uncommon step of explaining its position on Brainstorm's therapy in a press release.
"From data that have been communicated to the ALS community, there was a lot of hope that this product could provide at least a modest breakthrough in the management of ALS, if not something more substantial," the agency said. But, results from the late-stage study made it "clear that data do not support the proposed clinical benefit of this therapy."
Since then, The ALS Association has put out its own unusual release. Early this month, the group's Board of Trustees affirmed their support of Balas after she received "dangerous and vulgar social media attacks."