“Anything that shows any amount of activity counts,” added the Tex, Pico resident. Even a small change, Brous said, “could be the difference between signing my own name and having someone else sign 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, taking away their ability to walk, speak, and eventually breathe. Patients typically die within three to five years, but some live much longer with the condition sometimes called “Lou Gehrig’s disease” for the famous baseball player, who was diagnosed in 1939.
“This approval provides another important treatment option for ALS, a life-threatening disease that currently has no cure,” said Billy Dunn, director of the FDA’s Office of Neuroscience. 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 placebo, the agency said. Patients treated with the drug experienced a 25 percent slower decline in performing basic activities such as walking, talking, and cutting food compared to those taking a placebo.
Additionally, the FDA said a long-term analysis showed that patients who took Relyvrio at baseline lived longer compared to those who took a placebo. Amylyx, Cambridge, Mass., the biotech that makes the drug, said the survival benefit is a median of about 10 months.
During the drug’s review, FDA staff expressed concerns about the drug’s effectiveness and raised questions about the clinical trial. On Thursday, the agency accepted There were “limitations” in the data that caused uncertainty about the degree of effectiveness of the drug. However, the agency said regulatory flexibility was acceptable given the “serious and life-threatening nature of ALS and the significant unmet need for treatments.”
Amylyx officials said they plan to act as quickly as possible to make the drug available.
Co-CEOs Josh Cohen and Justin Klee said, “Amylyx’s goal is for everyone eligible to access Relyvrio as quickly and efficiently as possible, as we know people with ALS and their families don’t have time to wait.” Said. and expressions.
The company said that information on the price will be coming soon.
Patients, advocates, and ALS experts hailed what they called landmark confirmation. He says the drug represents a modest advance needed to make progress against the disease. About 30,000 people in the United States have ALS, and 6,000 new cases are diagnosed each year. Two other drugs are approved for the disease, but their effectiveness is extremely limited.
But some drug policy experts said there was not enough evidence that the drug worked. A 600-patient trial won’t be completed until late 2023 or early 2024.
“There is some evidence to support the product’s effectiveness, but I don’t think it hits the bar that the FDA typically requires,” said G. Caleb Alexander, MD, an internist and epidemiologist at the Johns Hopkins Bloomberg School of Public Health. He serves on the FDA advisory committee that reviews the drug. “How far should the FDA set the bar – if any – for products for a devastating disease without effective treatments”?
Diana Zuckerman, head of the National Center for Health Research, a think tank, agrees.
“How many ineffective ALS drugs do we need?” said Zuckerman. “It would be better to have someone proven to make a meaningful difference in living longer.”
However, Jinsy A. Andrews, associate professor of neurology and director of neuromuscular clinical trials at Columbia University, applauded the approval and said she plans to begin prescribing the drug as soon as possible. Other ALS experts agreed.
“I see patients living with this disease and I diagnose them every day,” Andrews said. “So having another therapy for the toolbox helps.” Andrews is a researcher in the large trial for the drug, which is currently underway.
The drug consists of two ingredients – a prescription drug called sodium phenylbutyrate, which is used to treat rare liver disorders, and a dietary supplement called taurrsodiol. The medicine comes as a water-soluble powder and can be swallowed or given through a feeding tube.
Two Brown University undergraduates — Cohen and Klee — came The idea for therapy was almost a decade ago, initially thinking it would be for Alzheimer’s disease.
ALS advocates said the approval demonstrates 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 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, of which $2.2 million was provided to help pay for testing AMX0035, the drug’s name during development. The drug is the first agency-funded drug to receive FDA approval. Amylyx has agreed to use the proceeds from the sale of the drug to repay 150 percent of its investment in the organization.
In 2019, Brian Wallach, who was in charge of the Obama White House, and his wife formed a group called I AM ALS after Wallach was diagnosed. This organization has made it a priority to bring the drug Amylyx to market.
The two groups pressed the FDA to be faster and more flexible in clearing ALS drugs, saying patients would accept treatments with increased safety risks in exchange for a small benefit — a perspective incorporated into the agency’s 2019 drug guidance. industry in developing ALS treatments. In 2020, two ALS organizations submitted more than 50,000 signatures to the FDA for approval of AMX0035.
As a do-it-yourself effort, some ALS patients in the United States are already taking the drug’s components. Because sodium phenylbutyrate is already approved, doctors may prescribe it off-label to ALS patients. The dietary supplement taurrsodiol, also called TUDCA, can be purchased online.
Steve Kowalski, 58, who lives in Boston and takes the components of the drug along with two other approved ALS drugs, says the regimen has slowed the worsening. With careful planning and the help of his three grown children, he could still go see his beloved Red Sox, but when he got home he said he was exhausted.
Kowalski welcomed the FDA action on the drug. He prefers to buy a high-quality, approved version of the drug rather than buying a supplement online.
The company’s application to the FDA foundation laid based largely on follow-up data from a single 24-week clinical trial and an ‘open-label’ study in which the drug was offered to all trial participants.
Typically, the FDA expects drug manufacturers to provide “significant evidence of efficacy” provided by two well-designed clinical trials. But the agency says a single trial may be sufficient if the study shows a “clinically significant and statistically very convincing effect” on prolonging survival or another aspect of the disease.
But in March, FDA staff issued a mostly negative report. evaluation — he suggested the data were not convincing — and the agency’s advisors agreed, voting 6-4 to recommend against FDA approval. Advocates said patients and advocates filled the FDA with more than 10,000 emails pleading for approval.
In a rare move, the FDA held a second advisory meeting this month to evaluate additional analysis submitted by the company. FDA staff once again memory He said there isn’t enough evidence of effectiveness to approve the drug.
But the tone of the meeting was different. distinctly from the first session. also exit, Dunn acknowledged that the data on the drug raises many questions, but also highlighted the “enormous unmet medical need” for ALS and the severity of the disease. He said the agency has the legal mandate to be flexible. And in a rather unusual move, Dunn asked Amylyx officials if they would voluntarily pull the drug off the market if the big trial failed; they said they would.
With several external experts on the advisory committee changing their positions, the panel proposed approval 7-2.
Controversy over the drug echoes the battle over the controversial Alzheimer’s drug Aduhelm, which was approved by the agency in June 2021. Critics said there was little evidence of the effectiveness of this drug, and Medicare refused to consider it outside of trials. The drug crashed on the market, Never quarrel with patients or doctors.
But ALS doctors insist that ALS medication is different. They noted that even though the benefit was modest, it achieved its primary goal in the trial. And they argued that even small gains make sense for people with the disease.
The FDA said the drug did not raise significant safety concerns; the most common adverse reactions are diarrhoea, abdominal pain, nausea and upper respiratory tract infection. The agency added that taurrsodiol, a bile acid, can cause worsening of diarrhea in patients with conditions that interfere with bile acid circulation, and urged them to speak to a specialist before seeking treatment.
Canada has recently provisionally approved the AMX0035. Amylyx may sell the drug there as long as the benefits of the treatment are confirmed by a larger trial.
