Despite concerns, FDA panel reverses course on ALS drug and recommends approval: shots

Drug maker Amylex is asking the FDA to approve a new drug for ALS, a deadly neurodegenerative disease. It is possible that the agency could give a green signal to the drug by the end of the month.

Manuel Balce Seneta / AP

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Manuel Balce Seneta / AP

Drug maker Amylex is asking the FDA to approve a new drug for ALS, a deadly neurodegenerative disease. It is possible that the agency could give a green signal to the drug by the end of the month.

Manuel Balce Seneta / AP

A controversial new drug likely to be approved by the Food and Drug Administration If by the end of the month.

But it’s still unclear whether a drug called AMX0035 actually helps people with ALS, a rare and fatal neurological disorder that eventually leaves a person unable to walk, talk, swallow, and breathe.

In March, the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee concluded that a study 137 of the ALS patients did not provide “sufficient evidence” that AMX0035 was effective.

Then in September, after being provoked by an email campaign by FDA officials and patients and their families, the same committee met again, and this time recommended approval of the drug.

The FDA, which typically follows advisory committee recommendations, has indicated it will make a decision by September 29.

An approval now more likely than it would have been decades ago, says Holly Fernandez LynchAssistant Professor of Medical Ethics and Health Policy at the University of Pennsylvania.

“The trajectory in the FDA has been increased willingness to accept weak evidence,” she says.

Two old products, one new drug

AMX0035 is a combination of two existing products. There is a dietary supplement called torsodiol, which can be purchased online. The other is a prescription drug called sodium phenylbutyrateWhich is used to treat a rare type of metabolic disorder.

The combination is meant to slow ALS, which gradually destroys cells in the brain and spinal cord that control voluntary muscle movement.

The AMX0035 was developed by Amylyx—a company based in Cambridge, Mass., founded in 2013 by two graduates from Brown University.

Amylyx sought FDA approval of its drug based on a single study of 137 patients with ALS. The results suggested that AMX0035 could extend patients’ lives by several months.

But at a public meeting in March, most experts on the FDA’s advisory committee said they disagreed with the study called Centaur.

Caleb Alexander, an epidemiologist at Johns Hopkins University, said: “The centaur has several characteristics that limit its causality.”

“The applicant has not provided strong evidence,” said Dr Brian Treynor, a neurologist at the National Institute on Aging.

“The data is not as strong as we would expect,” said Dr. Liana Apostolova, an Alzheimer’s specialist at Indiana University.

The study was “problematic,” said Dr., a neurogenetics researcher at the National Institutes of Health. Kenneth H. Fischbeck said.

Dr. Thomas J., a pathologist at Stanford University. “It didn’t meet the threshold,” Montin said.

“This study, by itself, does not establish that this drug is effective in treating ALS,” said Dr. Robert C. Alexander, chief scientific officer of the Alzheimer’s Prevention Initiative, led by the Banner Alzheimer’s Institute.

All six of those committee members voted no, when asked whether the evidence showed the drug was effective. Four other members of the committee voted yes.

advice to consultants

Normally, that kind of response would have been the end, at least until Amylix was ready to offer data from a great studywhich is already running.

But after the March meeting, ALS patients and family members took to the Internet.

“There were thousands of emails that went [FDA] Commissioner’s Office,” says Neel Thakur, chief mission officer at the ALS Association, which helped fund the Amylix study. “There were over 1,100 comments that went to the advisory committee itself, and there was continued effort from ALS clinical scientific leaders.”

The smaller clinical trial has flaws, Thakur said, but the advisory committee should have been prepared to overlook those when it first reviewed the evidence in the spring.

“They were asking to keep that drug to the same standard, they would keep any drug for any disease that wasn’t fatal and that had a lot of effective treatments,” he says.

Right now, only two drug variants are offered to ALS patients: edaravone And reluctance, And even with these drug treatments, they usually die within two to five years after diagnosis.

from no to yes

The email campaign of ALS patients had an impact on some FDA officials.

Earlier this month, the agency took the unusual step of re-convening its advisory committee to reconsider the Amylyx drug. And this time, the FDA encouraged committee members to take a different approach, Thakur says.

“This committee, it was clear that they were being asked to make decisions taking into account the treatment available and the needs of the ALS community,” he says.

The Committee also received some additional data on patients in the Amylyx study and data from the study of Alzheimer’s patients taking AMX0035.

When the committee held its second public meeting on medicine, it was offered guidance from Dr. Billy Dunno, which directs the FDA’s Office of Neuroscience. He urged them to consider the plight of ALS patients, and suggested that his agency be prepared to approve the drug.

“For these severe diseases, such as ALS and many other neurological diseases, the maximum degree of regulatory flexibility is on,” he said.

The FDA also revised its question to the committee. Instead of asking whether the drug was effective, he asked directly whether it should be approved.

After hearing – instead of six no votes, seven out of nine members decided to vote yes.

Echoes of Eduhelm?

Yes, the process leading to the vote was “messy”, says bioethicist Fernandez Lynch in UP.

“The very cynical version of this is that the advisory committee was some kind of target of manipulating the vote in a different way,” she says.

“They were swayed by concerns that they might make the wrong decision if they recommended the FDA not to approve this product,” she says. “But no one, as far as I’ve heard, has said that this drug meets the sufficient evidence standard.”

When the FDA was considering the controversial Alzheimer’s drug EduHelm, the adequate evidence standard was also in question. The FDA approved the drug last year that didn’t meet the standard, despite an overwhelming vote by an advisory committee.

If AMX0035 is approved, it could send a troubling message to drug companies, Lynch says.

“The message to companies is that you don’t have to show that your medicine works,” she says. “You have to do the least you can to show that it can work.”

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