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ALS drug approved by FDA in closely watched decision, marking win for patients, developer

The Food and Drug Administration on Thursday approved a new medicine for ALS, marking a major victory for patients and advocacy groups that have pressed the agency to bring forward more treatments for the fatal disease.

Known as AMX0035, the medicine took a winding journey as Amylyx Pharmaceuticals, its Massachusetts-based developer, sought to bring it to market. While clinical trial results indicate patients benefited from receiving AMX0035, FDA staff and some experts had remained skeptical about whether enough supportive evidence was collected.

The drug, like a few others in recent years, has tested the FDA’s flexibility toward potential therapies for brain and nervous system disorders. In 2021, the agency granted a controversial, first-of-its-kind approval to Biogen’s Aduhelm, an Alzheimer’s disease treatment that generated conflicting data in clinical studies. ALS advocates have pointed to that decision as one reason for the FDA to clear AMX0035.

The drug will be sold in the U.S. as Relyvrio — different from the brand name Albrioza that’s used in Canada, where it was authorized earlier this year. Amylyx will charge about $158,000 per year for Relyvrio in the U.S., roughly on par with another ALS medication the FDA approved in 2017.

That medication, called Radicava, is one of two commercially available to ALS patients in the U.S. The other, riluzole, was approved more than 25 years ago. Respectively, the therapies are meant to slow the functional decline associated with ALS and help patients live longer, though doctors note the effects of each are modest at best and temporary.

Amylyx’s drug is also far from a cure, as company co-founders Justin Klee and Josh Cohen readily acknowledge.

Yet, many patients have found it a source of hope, especially in light of how often ALS drug development has ended in failure. In the main study that led to Relyvrio’s approval, patients who received Amylyx’s drug declined slower than those who got a placebo, as measured by a 48-point scale used to evaluate the severity of ALS symptoms. Specifically, drug-treated patients scored about two points higher, on average, reflecting how well they performed daily functions like walking, swallowing or breathing.

Amylyx said additional analyses found Relyvrio also provided a survival benefit, with treated patients living on average almost five months longer than those on placebo.

While only a single study, the results are convincing for some ALS doctors. Rick Bedlack, director of the Duke ALS Clinic at Duke University, said in an interview ahead of the Relyvrio approval decision that he wants to prescribe the drug to his patients.

“This is the best result that I have seen in the history of ALS from one clinical trial,” he said. “It’s the only clinical trial I know of that showed both an effect on disability … and on survival.” Bedlack has consulted for Amylyx, but said he was not involved with the clinical research for Relyvrio.

Bedlack isn’t alone. In a Sept. 7 meeting, a panel of independent experts who advise the FDA on whether to approve new brain and nervous system drugs voted 7-2 in favor of Relyvrio. Though outstanding questions remain about the drug and the data backing it, the panel ultimately determined its benefits outweigh the risks.

Notably, these experts had met in March and came to the opposite conclusion, narrowly voting against Relyvrio. The FDA made the highly unusual move to reconvene its advisors when Amylyx submitted new analyses that, according to the company, reinforce the survival and functional benefits reported earlier.

In documents and at the September meeting, FDA officials both laid out their concerns with Amylyx’s data as well as highlighted the flexibility afforded to them in reviewing drugs for diseases like ALS.

“We are highly sensitive to the urgent need for the development of new treatments for ALS,” said Billy Dunn, director of the Office of Neuroscience in the FDA arm that evaluates new drugs, at the meeting.

Remarkably, Dunn called on Amylyx to commit to withdrawing Relyvrio from market should follow-up testing that’s now ongoing fail to confirm a benefit. Klee did, a pledge that at least one panelist cited in reversing his vote.

“This approval provides another important treatment option for ALS, a life-threatening disease that currently has no cure,” Dunn said in a statement Thursday. “The FDA remains committed to facilitating the development of additional ALS treatments.”

Relyvrio’s approval caps a decade of development that began at Brown University, where Klee and Cohen were then undergraduates studying neuroscience and biomedical engineering. They came up with a combination of two chemicals called sodium phenylbutyrate and taurursodiol, which prior research had suggested could protect the neurons that die as ALS progresses. Both compounds have been studied on their own as ALS treatments and some patients already take one or the other.

Preclinical testing conducted by Klee and Cohen went better than expected and they pushed the combination into a a small study as well as a larger clinical trial named CENTAUR, which became the main support for their approval application.

Although the results, published in The New England Journal of Medicine, were positive, the FDA initially signaled that it wanted Amylyx to run an additional trial before asking for approval — a stance that was criticized by patient groups like the ALS Association. The agency later relented, allowing the company to submit an application while it runs that confirmatory study.

“This [approval] is a victory for the entire ALS community, which came together to advocate for early approval of AMX0035,” said Calaneet Balas, CEO of the ALS Association, in a statement.

The group supported Amylyx’s research with $2.2 million in funding raised through the social media “Ice Bucket Challenge” that drew widespread attention to the disease in 2014.