The US Food and Drug Administration has approved a new treatment for amyotrophic lateral sclerosis, or ALS.
The FDA on Thursday announced the approval of Relyvrio, developed by Amylyx Pharmaceuticals. The oral drug can be taken as stand-alone therapy or with other treatments, according to the company, and has been shown to slow disease progression.
But there is still some uncertainty about the drug’s efficacy: Amylyx’s application for approval is based on data from a small phase 2 trial, and the FDA’s own advisory committee initially voted this spring that the data did not show the drug was cash, before changing his mind this month. A larger phase 3 study is still underway.
“There are limitations to these findings that result in a degree of residual uncertainty about the evidence of effectiveness that exceeds what might normally remain after the conclusion that substantial evidence of effectiveness has been demonstrated,” says an FDA. summary memorandum about approval. But “given the serious and life-threatening nature of ALS and the significant unmet need, this level of uncertainty is acceptable in this case.”
Amylyx said Friday that a 28-day prescription for Relyvrio will be priced at $12,504, about $158,000 per year, before insurance. Amylyx Chief Commercial Officer Margaret Olinger said during a conference call that it will provide financial assistance to reduce copays to $0 for people with commercial insurance, and will provide Relyvrio at no cost to people who are uninsured or underinsured who meet certain criteria. .
For people with Medicare and Medicaid, the company will provide financial assistance options.
Patients and some advocacy groups had urged the FDA to approve the drug as limited treatments are available for ALS. The agency granted priority review in December.
ALS, also known as Lou Gehrig’s disease, affects about 30,000 people in the United States. It is a neurodegenerative disease that causes muscles to weaken, ultimately affecting the ability to speak, swallow, move, and breathe.
“ALS is a horrible disease: rapidly fatal and really debilitating during the period from initial symptoms to death. The FDA has approved a couple of treatments, but they are minimally effective and certainly not a cure. So there is a huge unmet need in this disease area, which the FDA has recognized,” said Holly Fernandez Lynch, assistant professor of medical ethics and health policy at the University of Pennsylvania.
Before the FDA’s decision, Lynch told CNN she would be “shocked” if the drug was not approved because the FDA’s Central and Peripheral Nervous System Drugs Advisory Committee changed its opinion on the drug earlier this year. month, voting 7-2 in favor. of approval
Amylyx submitted a Drug Application to the FDA for the drug, then named AMX0035, as an oral treatment for ALS, seeking approval based on a Phase 2 trial that included 137 people with ALS who received either the drug or a placebo for 24 weeks. The study was funded in part by a grant from the ALS Ice Bucket Challenge, the viral social media campaign that began in 2014 in which people dumped buckets of ice water on themselves to raise awareness and funds around ALS.
The trial also showed that the drug was generally well tolerated, but there was a higher frequency of gastrointestinal events in the group receiving the drug. Amylyx is now continuing to study its safety and efficacy in a phase 3 trial.
In March, the Central and Peripheral Nervous System Drugs Advisory Committee voted 6-4 that a single Phase 2 trial failed to conclude that the drug is effective in treating ALS.
“In terms of drawing the conclusion that it’s effective, we were asked to persuasively and robustly seek substantial evidence, and I think this trial falls short of that standard,” said committee member Dr. Kenneth Fischbeck, a researcher at the National Institutes of Health, at the March meeting. Fischbeck added that he has treated ALS patients.
A key difference between the March and September FDA advisory committee meetings is that, at the subsequent meeting, Amylyx indicated that if the drug were approved but the Phase 3 trial results did not confirm the drug’s benefits, the company would consider withdraw the drug from the market. Lynch said. He added, however, that the company did not say specifically what it would see as a failure.
“So, on the vote, the members of the advisory committee changed and the majority said, ‘Yes, we are now convinced that this product should be approved.’ And when asked why they changed their minds, some said, ‘Well, the company said they were going to pull out,’” he said. “And they were also convinced by the patient testimonials that they really wanted to try this drug.”
But overall, the FDA approval was based on data from the Phase 2 trial, which, Lynch said, may send a message to other drug companies that they don’t need strong data from the Phase 3 trial to market. products.
Lynch said that while he understands why people with ALS want access to this promising drug, he is concerned that such a message could open the door more broadly to the approval of drugs that have not been shown to be effective. The FDA could later withdraw those products if necessary, she said, but doing so without a voluntary agreement from the company is “a huge pain” and often requires a lengthy process.
On Friday, Amylyx co-founder and co-CEO Justin Klee said that if the Phase 3 trial fails, the company will “always do what’s right for patients and for the community.”
“I guess, in short, why would we keep a drug on the market that doesn’t help people?” Klee said. “But the data we have to date is that Relyvrio showed an impact on function and survival in a disease that is rapidly progressive and universally fatal. So we have a responsibility to deliver to the community and what’s also right for the community is to continue to study the drug.”
Some ALS advocacy groups, including the ALS Association, have been supporting approval of Relyvrio for several months. After the FDA advisory committee meeting in March, when the panel initially voted against the drug, Calaneet Balas, president and CEO of the ALS Association, said in a statement that “the FDA has a decision to make: to approve Whether or not a drug that has been shown to be safe will help people living with ALS today, or whether it will delay approval and require more evidence as more people with ALS die.”
“We cannot let perfection get in the way of real progress in turning ALS from a deadly disease to a livable one. The FDA’s own ALS Guidance recognizes that people with ALS are willing to accept greater risk for the possibility of some benefit,” Balas said. “People with ALS and their loved ones deserve better, and the FDA has the tools to do it urgently.”