“Anything that shows some degree of efficacy is important,” the Pico, Texas, resident added. Even a small change, Brous said, “could be the difference between signing my own name and having someone else sign it for me.”
The newly approved therapy, to be sold under the brand name Relyvrio, is designed to slow the disease by protecting nerve cells in the brain and spinal cord destroyed by ALS, amyotrophic lateral sclerosis. The ailment paralyzes patients, depriving them of their ability to walk, speak and eventually breathe. Patients usually die within three to five years, although some live much longer with the condition sometimes called “Lou Gehrig’s disease” because the renowned baseball player was diagnosed in 1939.
“This approval provides another important treatment option for ALS, a life-threatening disease that currently has no cure,” Billy Dunn, director of the FDA’s Office of Neuroscience, said in a statement.
The agency said the efficacy of Relyvrio, the first new approved therapy for ALS in five years, was demonstrated in a 24-week study in which 137 patients were randomly assigned to receive Relyvrio or a placebo. Patients treated with the drug experienced a 25 percent slower rate of decline in performing essential activities, such as walking, talking and cutting food, compared to those given a placebo.
In addition, the FDA said, a long-term analysis showed that patients who originally received Relyvrio vs. those who took the placebo lived longer. Amylyx, the Cambridge, Massachusetts, biotech company that makes the drug, said the survival benefit was a median of about 10 months.
During drug reviews, FDA staff raised concerns about the drug’s effectiveness and raised questions about the clinical trial. On Thursday, the agency admitted there were “limitations” in the data that created uncertainty about how effective the drug was. But the agency said the regulatory flexibility was acceptable due to the “serious and life-threatening nature of ALS and the substantial unmet need” for treatments.
Amylyx officials said they plan to act as quickly as possible to make the drug available.
“[Amylyx’s] The goal is for every person who is eligible for Relyvrio to have access as quickly and efficiently as possible, as we know people with ALS and their families don’t have time to wait,” Co-Executive Directors Josh Cohen and Justin Klee said in a statement. a statement.
The company said pricing information will be coming soon.
ALS patients, advocates and specialists hailed what they called a landmark approval, say that the drug represents the kind of modest breakthrough needed to make progress against the disease. About 30,000 people in the United States have ALS, with 6,000 new cases diagnosed each year. Two other drugs, including Radicava, which hit the US market in 2017, are approved for the ailment but have extremely limited effectiveness.
However, some drug policy experts said there is not enough evidence that the drug works. A trial with 600 patients will not be completed until late 2023 or early 2024.
“There is some evidence to support the efficacy of the product, but I don’t think it reaches the level that the FDA usually requires,” said G. Caleb Alexander, an internist and epidemiologist at the Johns Hopkins Bloomberg School of Public Health, who is a member of the advisory committee. from the FDA that reviewed the drug. “How much, if ever, should the FDA lower the bar for products for a devastating disease” that lacks effective treatments?
Diana Zuckerman, president of the National Center for Health Research, a think tank, agreed.
“How many ineffective drugs for ALS do we need?” Zuckermann said. “You’d be better off having one that has been shown to make a significant difference in living longer.”
But Jinsy A. Andrews, an associate professor of neurology and director of neuromuscular clinical trials at Columbia University, applauded the approval and said she plans to start prescribing the drug as soon as it’s available. Other ALS specialists agreed.
“I see patients living with this disease and I diagnose them every day,” Andrews said. “So having another therapy for the toolkit is helpful.” Andrews is an investigator in the large trial of the drug that is currently underway.
The drug consists of two components: a prescription drug called sodium phenylbutyrate that is used to treat rare liver disorders, and a nutritional supplement called taurursodiol. The medication comes as a powder that dissolves in water and can be swallowed or given through a feeding tube.
Two college students from Brown University – Cohen and Klee – arose with the idea of the therapy nearly a decade ago, initially thinking it would be for Alzheimer’s disease.
ALS advocates said the approval shows the importance of getting patients and advocates involved in efforts to bring drugs to market.
“We still have a lot of work to do to cure ALS, but this new treatment is a significant step in that fight,” said Calaneet Balas, president and CEO of the ALS Association.
In 2014, the organization raised $115 million in six weeks of the Ice Bucket Challenge and provided $2.2 million to help pay for testing of AMX0035, the name of the drug during development. The drug is the first funded by the organization to receive FDA approval. Amylyx agreed to use proceeds from drug sales to pay the organization 150 percent of its investment.
In 2019, Brian Wallach, an Obama White House staffer, and his wife founded a group called I AM ALS after Wallach was diagnosed. That organization made the commercialization of the drug Amylyx a priority.
The two groups pushed the FDA to be quicker and more flexible in approving ALS drugs, saying patients would accept treatments with higher safety risks for a small benefit, a view built into the guidance. of the 2019 agency for the pharmaceutical industry. industry in developing therapies for ALS. In 2020, the two ALS organizations submitted more than 50,000 signatures to the FDA seeking approval of AMX0035.
In a DIY effort, some ALS patients in the United States are already taking the drug’s ingredients. Because sodium phenylbutyrate was already approved, doctors can prescribe it off-label to ALS patients. Taurusodiol nutritional supplement, also called TUDCA, can be purchased online.
Steve Kowalski, 58, who lives in Boston and takes the drug’s components, along with the other two approved ALS drugs, credits the regimen for slowing his decline. With careful planning and the help of his three adult children, he can still go see his beloved Red Sox, but he’s exhausted when he gets home, he said.
Kowalski welcomed the FDA’s action on the drug. He prefers to get a high-quality, approved version of the drug rather than having to buy a supplement online.
The company’s application to the FDA. was based largely on the 24-week clinical trial and follow-up data from an “open label” study in which the drug was offered to all trial participants.
The FDA generally expects drugmakers to submit “substantial evidence of efficacy” provided by two well-designed clinical investigations. But the agency says that a single trial may suffice if the study demonstrates a “clinically significant and statistically highly persuasive effect” on the extent of survival or some other aspect of the disease.
In March, however, FDA staff issued a largely negative report. evaluation — suggesting the data was not persuasive — and agency advisers agreed, voting 6-4 to recommend against FDA approval. Patients and advocates flooded the FDA with more than 10,000 emails asking for approval, advocates said.
In an unusual move, the FDA held a second advisory meeting this month to consider additional tests submitted by the company. Once again, FDA staff suggested in a memorandum that there was not enough evidence of effectiveness to approve the drug.
But the tone of the meeting differed notably from that of the first session. In the beginning, Dunn acknowledged that the drug data raised numerous questions, but also emphasized the “tremendous unmet medical need” for ALS and the severity of the disease. He said the agency had the legal authority to be flexible. And in a highly unusual move, Dunn asked Amylyx officials if they would voluntarily withdraw the drug from the market if the big trial failed; they said they would.
With some of the outside experts on the advisory committee changing positions, the panel recommended approval 7-2.
The debate over the drug has echoes of the battle over Aduhelm, the controversial Alzheimer’s drug approved by the agency in June 2021. Critics said there was little evidence of efficacy for that drug, and Medicare refused to cover it except in trials. . The drug collapsed on the market., never gaining traction with patients or doctors.
But ALS doctors insist that ALS medication is different. It reached its primary endpoint in the trial, even if the benefit was modest, they noted. And even small gains are significant for people with the disease, they argued.
The FDA said the drug did not pose any major safety concerns; the most common adverse reactions were diarrhea, abdominal pain, nausea, and upper respiratory tract infection. The agency added that the bile acid taurursodiol can worsen diarrhea in patients with disorders that interfere with the circulation of bile acid, and urged those people to talk to a specialist before taking the treatment.
Canada recently approved AMX0035 conditionally. Amylyx can sell the drug there, as long as the benefits of the treatment are confirmed by the larger trial.
