After Amylyx ALS trial failure, patients share disappointment and fear — but some hope

The news last week that a Phase 3 trial of Amylyx Pharmaceuticals’ amyotrophic lateral sclerosis drug — marketed as Relyvrio — failed to benefit patients compared to placebo hit the ALS patient community hard.

An earlier study had shown that patients who took the drug for six months experienced significantly less decline than people on the placebo in physical function, such as the ability to speak, use utensils, or climb stairs. But while the Phase 2 results led to the drug’s approval by the Food and Drug Administration in 2022, they failed to replicate in a larger group.

That outcome has broad consequences for Amylyx Pharmaceuticals, other companies developing ALS drugs, physicians, and, most of all, patients who lost yet another possible treatment for a merciless disease. STAT spoke with a few of them who, despite the challenges of their disease — including speech impairment — shared varying perspectives on what the news meant to them and their patient communities, and what hope looks like after this latest setback.

‘This was by no means a failure’

Gwen Petersen, 38, who has had ALS for close to six years, has been taking Relyvrio since 2022, and her disease stabilized while she was on the drug. That meant everything to her, and she was hopeful those benefits came from the treatment itself, though some ALS patients see their disease stabilize for months or even years even in the absence of effective treatments. In light of the trial results, she plans to reach out to her neurologist to understand the next steps for her treatment.

“I was not expecting this outcome given the positive results and survival data we got from Phase 2,” said Gwen Petersen. “The number-one question is what do I do? Do I stop taking this?”

The Southport, Conn. resident is worried that the trial results will make it harder than it already is to get insurance coverage for the drug, adding that in the past she had to spend months filing paperwork to get coverage for Relyvrio and that her coverage was discontinued once. After this latest trial, she believes insurers will be more reluctant to pay for the medication. Amylyx charged $163,000 per year for the therapy. And if the treatment is pulled from the market, an option Amylyx’s co-CEOs have made clear is on the table, she’ll lose access to Relyvrio altogether. The company’s executives plan to make a final decision within the next eight weeks.

Drug companies may also be less incentivized to undertake research in ALS, Petersen said. “If I was a drug developer, I wouldn’t want to touch ALS with a 10-foot pole,” she said, noting that many of the companies in the field are relatively small and may not have the resources to make big bets on new drugs. “I’m scared, quite frankly.”

But Petersen also has some hope left. She spoke with STAT shortly before a trip to France with a group of friends — all young women living with ALS — and she’s looking forward to the town hall Amylyx has promised to hold with patients. She has submitted advanced questions for the event, including whether there is any new biomarker data that emerged from the trial. “There are insights to be gleaned from the data and how we conduct clinical trials in the future. So this was by no means a failure.”

‘We’re not a lost cause’

“The news about Relyvrio is very, very disappointing,” said John Russo, 68, of Southampton Township, N.J. “I have had ALS for about 11 years and have been waiting that long for something to help slow the disease even more than just riluzole, which I have been taking since 2013.”

Russo, who is an advocate with ALS United Mid-Atlantic, has not taken Relyvrio, but he knows people who have. And, like Petersen, he notes that it’s hard to say whether the drug is having an effect based on an individual response. “We don’t really know if the drugs we take are helping. We hope they are, but we really don’t know,” he said. “It would be difficult to put a finger on the results of taking the drug from the patient’s perspective. We don’t tend to feel better — we just get to live longer.”

But Russo, too, maintains a degree of hope. “I am happy that there is so much research going on worldwide on this disease, as it does prove to me that we’re not a lost cause,” he said. “These researchers wouldn’t spend their time, or dedicate their careers, to a hopeless disease.”

‘You’re removing hope’

Unlike other patients, Phil Green, 54, was not surprised to see the trial results. “This one-size-fits-all approach to determine drug efficacy will almost always lead to negative outcomes,” said Green, who was not involved in any Amylyx trials and doesn’t currently take Relyvrio but who has been an adviser to Amylyx. “I think one of the biggest challenges with ALS is figuring out what works for who. The approval agencies continue to lump everybody in the same bucket, but the reality is some therapies may work better for some phenotypes than others, so lack of efficacy in one will drag down the overall scoring.”

The Temecula, Calif. resident sees two immediate problems arising from the trial results. The first is insurance coverage. The second issue may not be quite as practical, but is arguably bigger. “The therapies in ALS, they represent hope in our hopeless disease. By removing a therapy off the market, you’re removing hope,” he said.

‘If we fail, we get up again and again’

“My hope was that this drug would keep people — my friends — alive while research for a cure continued,” said Katrina Byrd, 52, in a note written to STAT.

Byrd, an advocate who lost her partner of 23 years, Dora, to ALS, testified in favor of Relyvrio in front of the FDA alongside her friends, ALS patients Becky Mourey and Sandy Morris, who have since died. She said the results of the trial were both unexpected and disappointing.

For her, the trial exacerbates her worries about drug affordability — something she is very aware of given her limited income. “As a person living under the poverty line, I was very concerned about drug pricing. Unfortunately, I’ve accepted [that] when you can’t afford basics like food and clean water, access to promising therapies are out of reach,” she said. “It breaks my heart that these therapies are also unavailable to affluent, middle class families, and veterans.”

To Byrd, a Jackson, Miss. resident, the trial’s outcome is just one of the many devastating realities people with ALS face each day.

“A wheelchair doesn’t cure ALS. The right type of bed, a remodified home or an accessible van doesn’t cure ALS. Money, race or class does not cure ALS. The impact of ALS on the body, the family, the spirit, is grueling, relentless, haunting,” she said. “If Lou Gerhig were diagnosed today he would still have the same prognosis — death.”

Yet Byrd still finds strength in the community of patients and their friends and families. “So, what do we do? We keep going. With our emancipated bodies, broken hearts, and broken spirits, we stand together and demand to be a part of the ALS drug development process. If we fail, we get up again and again.”

The story has been corrected to reflect the fact that Katrina Byrd was speaking as an ALS advocate and not as someone with ALS.