Publisher Health

An experimental therapy for A.L.S., the paralyzing and fatal neurological disorder, has been approved in Canada, adding a new treatment option for a disease for which there are few effective therapies.

The approval, which comes with the condition that the drug company later provide better evidence that the treatment works, is likely to be of major interest to patients with A.L.S. (amyotrophic lateral sclerosis) in the United States, where the same therapy — AMX0035, to be marketed as Albrioza — is being evaluated by the Food and Drug Administration, which has raised questions about the treatment’s effectiveness.

An F.D.A. review earlier this year found Albrioza to be safe, but said there was not enough evidence that it was effective either in helping patients live longer or slowing the rate at which they lose functions like muscle control, speaking or breathing without assistance. A committee of independent advisers to the F.D.A. voted by a narrow margin in March that the therapy was not ready for approval.

The F.D.A. had been scheduled to issue a final decision this month, but recently extended the deadline to Sept. 29, saying it needed more time to review additional analyses of data submitted by the company.

In the meantime, Calaneet Balas, president and chief executive of the A.L.S. Association, one of several patient advocacy organizations pressing for F.D.A. approval, said, “We expect that Americans living with A.L.S. will try to access Albrioza in Canada, just as we have heard reports of people trying to buy the ingredients on Amazon.”

A.L.S., also called Lou Gehrig’s disease, is diagnosed in about 6,000 people worldwide each year and often causes death within two to five years. There are only two approved A.L.S. medications in the United States: riluzole, which can extend survival by several months, and edaravone, which can slow progression by about 33 percent.

Albrioza is a combination of two existing drugs in the form of a bitter-tasting powder that is mixed with water and drunk or ingested through a feeding tube twice daily. It is produced by a small Massachusetts company, Amylyx Pharmaceuticals, whose founders, Justin Klee and Joshua Cohen, conceived of the therapy when they were undergraduate students at Brown University less than a decade ago.

Their idea was that combining taurursodiol, a supplement sometimes used to regulate liver enzymes, and sodium phenylbutyrate, a medication for a pediatric urea disorder, could safeguard neurons by preventing dysfunction of two structures in cells: mitochondria and the endoplasmic reticulum.

The data comparing Albrioza to a placebo has so far come from one Phase 2 trial (which is smaller than the Phase 3 studies regulatory agencies generally require); additional information came from an open-label extension study that followed some patients after the trial ended, when they were knowingly taking the medication. The F.D.A. typically requires two persuasive clinical trials of a drug for approval, but in cases of severe disease with few available treatments, it can consider evidence from one clinical trial plus additional supporting data.

Health Canada greenlighted Albrioza under a program called Notice of Compliance with Conditions, which allows for approval of drugs that appear promising for serious diseases, but have incomplete evidence that they work. The central condition the agency set is that Amylyx “verify the clinical benefit of this drug” with data from a Phase 3 clinical trial that is underway and expected to conclude in 2024, according to agency documents sent to the company on Friday. The company must also conduct additional pharmacological studies and provide periodic safety reports. “Patients should be advised of the nature of the authorization,” the documents said.

The F.D.A. has a similar program called accelerated approval that allows conditional approval of drugs with incomplete evidence of effectiveness, but that program also requires that a drug show that it targets part of the underlying biological mechanism of a disease. Experts have said that if Albrioza does not win standard F.D.A. approval, it would be unlikely to meet accelerated approval criteria because too little is known about the underlying biology of A.L.S., and how and whether Albrioza might address it.

Last month, 38 doctors who treat A.L.S. patients sent a letter to the F.D.A. urging approval. The A.L.S. Association said its campaign for approval had in recent weeks generated more than 6,000 emails asking the agency to greenlight the drug.

A member of the F.D.A.’s independent advisory committee, Dr. G. Caleb Alexander, who voted in March that there was insufficient evidence the therapy works, said he continues to think the F.D.A. should wait for the Phase 3 trial’s results and that “it would be a mistake to approve it based on the single trial alone.”

Dr. Alexander, an internist and epidemiologist at the Johns Hopkins Bloomberg School of Public Health, said there was desperate need for effective therapies for A.L.S., but that for Albrioza, “it’s unfortunate, but the magnitude of unmet need is not matched by the quality of evidence to date.”

He added that “approval in Canada could only further increase the pressure that the F.D.A. faces to rule favorably and to approve this product.”

It is generally illegal for Americans to import drugs that haven’t been approved in the U.S. for personal use. But the F.D.A. website lists some exceptions that might apply to Albrioza, including if the drug has no serious safety issues and if it is to treat “a serious condition for which effective treatment is not available in the United States.”

Dr. Angela Genge, director of the A.L.S. Global Centre for Excellence at the Montreal Neurological Institute, who has received fees from Amylyx for serving on an advisory board, said American patients would be legally able to receive Albrioza in Canada if it were prescribed by a Canadian physician and obtained from a Canadian pharmacy, though they would not be eligible for insurance coverage under Canada’s public or private system.

In an interview, Mr. Cohen and Mr. Klee declined to disclose the price that Amylyx is considering for Albrioza, saying it was still being negotiated. They said that the therapy would be available in about six weeks for people who were paying privately, but would take longer, possibly months, for people to receive coverage under Canada’s public system. Amylyx has already been providing Albrioza at no cost under compassionate-use arrangements to 250 patients in the United States, they said.

Until last summer, the F.D.A. had recommended that Amylyx not apply for approval until the drug had completed its Phase 3 trial, but in July, officials began suggesting that Amylyx submit an application for approval using existing data. The timing followed vociferous pressure from A.L.S. advocacy groups in the wake of the approval of the new Alzheimer’s drug, Aduhelm, which was controversial because many experts said there was insufficient data that Aduhelm worked.

In the Phase 2 trial, two-thirds of the 137 participants received Albrioza, and over 24 weeks, they experienced a 25 percent slower decline than the participants receiving placebo — declining 2.32 points less on a 48-point A.L.S. scale that rates 12 physical abilities, including walking, speaking, swallowing, dressing, handwriting and breathing.

The open-label extension study involved 90 of those patients, including 34 from the placebo group, who began taking the medication about seven months after those who had received it from the beginning. Those who received the treatment the longest had a median of 4.8 months more time before being hospitalized, being put on a ventilator or dying, Amylyx reported. Researchers involved in the study published more data last month that suggested additional benefit.

Amylyx financed the bulk of its research on Albrioza, but the A.L.S. Association contributed $2.2 million, using money raised through the 2014 Ice Bucket Challenge. Amylyx has agreed to use sales of the drug to repay 150 percent of the association’s grant to fund more research.

The clinical trials involved patients who developed symptoms within 18 months before the trial and were affected in at least three body regions, generally signs of fast-progressing disease. Health Canada’s approval did not place restrictions on which A.L.S. patients could take Albrioza, but the Amylyx founders and Dr. Genge said it is possible that such limitations might be established by the Canadian coverage system or by pharmaceutical formularies in some of Canada’s provinces.