“Anything that shows any effect is important,” the Pico, Tex., resident added. Even a small change, Brous said, “can be the difference between signing my own name and someone else signing it for me.”
The newly approved treatment, which will 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 disease paralyzes patients, robbing them of the ability to walk, talk 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” for the renowned baseball player 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 treatment approved for ALS in five years, was demonstrated in a 24-week study in which 137 patients were randomized to receive Relyvrio or a placebo. The patients treated with the drug experienced a 25 percent slower decline in performing important 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 initially received Relyvrio versus those who took a placebo lived longer. Amylyx, the Cambridge, Mass., biotech that makes the drug, said the survival benefit was a median of about 10 months.
During reviews of the drug, FDA staff expressed concerns about the drug’s effectiveness and raised questions about the clinical trial. On Thursday, the agency acknowledged that there were “limitations” to the data that resulted in uncertainty about the drug’s degree of effectiveness. But the agency said regulatory flexibility was acceptable because of the “severe and life-threatening nature of ALS and the significant unmet need” for treatments.
Amylyx officials said they plan to move as quickly as possible to make the drug available.
“Amylyx’s goal is that every person eligible for Relyvrio will have access as quickly and efficiently as possible, as we know that people with ALS and their families do not have time to wait,” said co-chief executive officers Josh Cohen and Justin Klee in a statement.
The company said that information about the price will come soon.
Patients, advocates and ALS specialists hailed what they called a landmark approval, says the drug represents the kind of modest progress 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 are approved for the disease, but have extremely limited effectiveness.
However, some drug policy experts said there is insufficient evidence that the drug works. A study of 600 patients will not be completed until late 2023 or early 2024.
“There is some evidence to support the effectiveness of the product, but I don’t think it hits the threshold that the FDA typically requires,” said G. Caleb Alexander, an internist and epidemiologist at the Johns Hopkins Bloomberg School of Public Health who serves on the FDA’s advisory committee that reviewed the material. “How much should the FDA lower the bar — if at all — 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 ALS Drugs Do We Need?” Zuckerman said. “It would be better to have one that has been shown to make a meaningful 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 is available. Other ALS specialists agreed.
“I see patients living with this disease and I diagnose them every day,” Andrews said. “So it’s useful to have another therapy for the toolkit.” Andrews is an investigator in the major drug trial that is currently underway.
The drug consists of two components – a prescription drug called sodium phenylbutyrate used to treat rare liver diseases and a dietary supplement called taurursodiol. The medicine comes in a powder that is dissolved in water and can be swallowed or given through a feeding tube.
Two students from Brown University – Cohen and Klee – came up with the idea for the therapy nearly a decade ago, initially thinking it would be for Alzheimer’s disease.
Advocates for ALS said the approval shows the importance of patients and advocates getting involved in the effort to bring drugs to market.
“We still have a lot of work to do to cure ALS, but this new treatment is an important step in that fight,” said Calaneet Balas, president and CEO of the ALS Association.
In 2014, the organization raised $115 million in six weeks from the Ice Bucket Challenge and gave $2.2 million of that to pay for testing of AMX0035, the drug’s name in development. The drug is the first funded by the organization to receive FDA approval. Amylyx has agreed to use the proceeds from the sale of the medicine to repay the organization 150 percent of the 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 prioritized getting the Amylyx drug onto the market.
The two groups pushed the FDA to be faster and more flexible in removing ALS drugs, saying patients would accept treatments with increased safety risks in return for even a small benefit — a view embodied in the agency’s 2019 guidance to the pharmaceutical. industry to develop ALS therapies. In 2020, the two ALS organizations submitted more than 50,000 signatures to the FDA requesting approval of AMX0035.
In a do-it-yourself effort, some ALS patients in the United States are already taking the ingredients in the medicine. Because sodium phenylbutyrate was already approved, doctors can prescribe it off-label to ALS patients. The food supplement taurursodiol, also called TUDCA, can be bought online.
Steve Kowalski, 58, who lives in Boston and takes the components of the drug, along with the other two approved ALS drugs, credits the regimen with slowing his deterioration. With careful planning and help from his three grown children, he can still watch his beloved Red Sox, but is exhausted when he gets home, he said.
Kowalski welcomed the FDA action on the drug. He prefers to get an approved, high-quality version of the medicine rather than buying a dietary supplement online.
The company’s application to the FDA was largely based on the single 24-week clinical study and follow-up data from an “open label” study in which all trial participants were offered the drug.
Generally, the FDA expects drug manufacturers to submit “substantial evidence of effectiveness” provided by two well-designed clinical trials. But the agency says a single study may be sufficient if the study shows a “clinically meaningful and statistically very convincing effect” on prolonging survival or another aspect of the disease.
In March, however, FDA staff issued a mostly negative review — suggesting the data were not convincing — and the agency’s 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 a rare move, the FDA held a second advisory meeting this month to consider additional analyzes provided by the company. Once again, FDA staff suggested in a memo that there was not enough evidence of effectiveness to approve the drug.
But the tone of the meeting was different markedly from the first session. At the outset, Dunn acknowledged that the data for the drug raised a number of questions, but also emphasized the “huge unmet medical need” for ALS and the severity of the disease. He said the agency had 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 large trial failed; they said they would.
With a few of the outside experts on the advisory committee changing their 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 substance collapsed in the marketplace, never get hold of patients or doctors.
But ALS doctors insist the ALS drug is different. It achieved its primary goal in the trial, although the benefit was modest, they noted. And even small gains are meaningful for people with the disease, they argued.
The FDA said the drug did not pose major safety concerns; the most common side effects were diarrhoea, abdominal pain, nausea and upper respiratory tract infection. The agency added that taurursodiol, a bile acid, can cause worsening of diarrhea in patients with disorders that interfere with bile acid circulation and urged these people to talk to a specialist before taking the treatment.
Canada recently approved AMX0035 on a conditional basis. Amylyx can sell the drug there, as long as the treatment’s benefits are confirmed by the larger study.