ALS drug fails large clinical trial and may be withdrawn from market

By Mira Cheng, CNN

(CNN) — Amylyx Pharmaceuticals announced Friday that its drug for amyotrophic lateral sclerosis, or ALS, called Relyvrio, did not show significant benefit in a large clinical trial and may be withdrawn from the market.

New results from a large phase 3 clinical trial, called Phoenix, showed that the drug did not outperform a placebo in improving participants’ ALS functional scale, a measure of their ability to breathe, swallow and speak after 48 weeks. It also did not significantly improve patient-reported quality of life, overall survival and respiratory function.

“We are surprised and deeply disappointed by the PHOENIX results,” Justin Klee and Joshua Cohen, co-CEOs of Amylyx, said in a news release. “Over the next eight weeks, our team will continue to engage with regulatory authorities and the ALS community to discuss the results from PHOENIX. We will be led in our decisions by two key principles: doing what is right for people living with ALS, informed by regulatory authorities and the ALS community, and by what the science tells us.”

Amylyx said the discussions in the next eight weeks may include the withdrawal of Relyvrio from market. In the meantime, the drug and patient support services are still available for people living with ALS; however, the company has paused promotion of Relyvrio.

“We are saddened by today’s news and our hearts go out to everyone in the ALS community, which desperately needs new safe and effective treatments,” the nonprofit ALS Association said in an email to CNN. “We are grateful to the FDA and Amylyx for working closely with the ALS community throughout this process.”

ALS, also known as Lou Gehrig’s disease, affects as many as 30,000 people in the United States. It’s a fatal neurodegenerative disease that kills the nerves that make muscles work, affecting the ability to move, speak, swallow and eventually breathe, according to the US Centers for Disease Control and Prevention. The average time from symptom development to death is two to five years.

“ALS is a terrible disease. There are no good treatment options,” said Holly Fernandez Lynch, assistant professor of medical ethics and law at the University of Pennsylvania. “There is an insatiable desire to develop something that is going to modify the course of this disease.”

Relyvrio gained approval from the US Food and Drug Administration in September 2022 based on a small phase 2 trial that showed a modest slowing of disease progression in people who received the drug. But the decision was controversial, as proof of the drug’s efficacy at that point was insufficient by typical FDA standards, Fernandez Lynch said.

“In terms of establishing the conclusion that it’s effective, we were asked to look for substantial evidence with persuasiveness and robustness, and I think this one trial doesn’t quite meet that bar,” Dr. Kenneth Fischbeck, a member of the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee and an investigator at the National Institutes of Health, said at a meeting in March 2022.

However, after extensive lobbying by ALS patient advocacy groups and a promise from the company that it would consider withdrawing the drug if the larger phase 3 trial failed to confirm benefits, the advisory committee changed its mind and voted in favor of approval, Fernandez Lynch said.

“Had the FDA not approved early and then the PHOENIX trial results had been positive, thousands of people living with ALS would have not had access to a life-extending treatment that was safe for over two years,” the ALS Association said in its statement. “Our community expressed to the FDA that they were willing to take the risk if it turned out to be ineffective.”

Now that the phase 3 results show that the drug is ineffective, it is up to Amylyx Pharmaceuticals to withdraw the drug, Fernandez Lynch said. If the company decides against doing so, the FDA retains the power to pull the drug from market, but it would be a much more drawn-out process, she added.

Fernandez Lynch said that while she thinks the gamble the FDA made in this case was reasonable, she has concerns about how much money Amylyx made from selling a drug that does not work.

Relyvrio costs about $158,000 per year and generated $381 million in sales and $49 million in profits for Amylyx in 2023, according to the company’s full year financial results.

“I think this is an example where, if you’re going to allow drugs on the market with uncertainty, then we need to have greater control over the pricing,” Fernandez Lynch said.

CNN’s Jacqueline Howard contributed to this report.

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