A federal panel of independent medical experts concluded Wednesday that there is not enough evidence that a new experimental therapy for amyotrophic lateral sclerosis is effective in treating the devastating and fatal neurological disorder.
The FDA advisory panel voted 6 to 4 that the data on the therapy was not strong enough to show that it could slow the progression of A.L.S.
The analysis by the F.D.A. was supported by the nonbinding vote on the therapy. The agency will make a decision on the drug in the coming months.
The groups representing A.L.S. patients have waged a campaign for the therapy to be approved, given the lack of medications for the disorder, which often causes death within two to five years. The groups met with F.D.A. officials and members of Congress after a petition drive received more than 50,000 signatures.
The committee members who voted against the therapy said it was difficult for patients to be disappointed.
There is a huge unmet need for safe and effective treatment and there is a burdensome nature to the disease. I think this trial doesn't meet that bar.
Mark Weston was the patient representative on the panel and he voted that the treatment was effective. The director of the National Institute of Neurological Disorders and Stroke said it was a very difficult decision to make. I hedged my bets after considering all the facts and factors.
Some of the people living with A.L.S. had lost so much of their ability to speak that some of their words were read by family members.
He had to have his food cut for him, and he needed assistance to pull up his pants. He said that he has been able to do construction work on a deck, walk many miles in Europe, and go to the Great Wall of China with his wife since he participated in the AMX0035 clinical trial.
He said that AMX0035 is a life-changing drug.
A.L.S. was likened to inflatable punching bags by a musician who was diagnosed with the disorder in 2020.
It is time to take a step in the right direction towards meeting the critical unmet need of the disease, said Ms. Mourey in her own voice. I urge you to recommend approval of AMX0035.
The National Center for Health Research testified that the F.D.A. should not approve the therapy without stronger evidence of effectiveness.
In cases of severe disease with few available treatments, the F.D.A. can make exceptions and consider evidence from one clinical trial plus some additional supporting data. The data from the Phase 2 clinical trial was smaller than the preferred Phase 3 studies and included additional information from the patients after the trial ended.
In June of last year, the F.D.A. approved the Alzheimer's drug Aduhelm despite conflicting scientific results from two trials. The drug was approved and three members of the committee resigned.
The same F.D.A. department that reviewed Aduhelm, the Office of Neuroscience, and the same advisory committee had a hearing on Wednesday.
Some of the features are similar in that you have an incredible demand for new treatments for a devastating disease in the midst of murky evidence that really doesn't point in a clear direction. He did not vote Wednesday.
The manufacturer of the new A.L.S. therapy, Amylyx Pharmaceuticals, was not allowed to apply for approval until it had completed a Phase 3 trial, which the company started in 2021, according to the F.D.A. F.D.A. officials sent an email asking the company to meet to discuss submitting an application for approval.
The application was filed in September. The timing followed vociferous pressure from A.L.S. advocacy groups in the wake of the approval of Aduhelm, and in testimony from advocates and patients Wednesday, several said that if the agency could approve an Alzheimer's drug with questionable efficacy, it should approve AMX.
About 6,000 people are diagnosed with A.L.S. each year. There are only two approved A.L.S. medications, riluzole and edaravone.
A decade ago, Mr. Klee and Mr. Cohen were students at Brown University, and they proposed that a combination of two drugs could be used.
sponsoring.
The A.L.S. Association, a patient advocacy group, contributed $2.2 million in funding, using money raised through the Ice Bucket Challenge, which brought in about $220 million. Amylyx agreed to use a percentage of income from sales of the drug to repay the association's grant.
The Phase 2 clinical trial involved 137 patients who had developed symptoms of A.L.S. within 18 months before the study began and who were affected in at least three body regions, a sign that the disease is progressing quickly. Two-thirds of patients received a bitter-tasting powder that they mixed with water to drink or ingest through a feeding tube. A placebo was given to the rest.
The primary goal was to slow the decline on the A.L.S. scale. Patients receiving a placebo declined 2.32 points more than those taking the drug combination, which resulted in a 25 percent slower decline for patients receiving the treatment.
The open-label extension study involved 90 patients, including 34 from the placebo group, who began taking AMX0035 about seven months after receiving it. The researchers reported that those who received the longest treatment had a median of almost five months more to live.
This is the first time that we have seen a benefit in both function and survival in an A.L.S. clinical trial.
Patients in my clinic may never receive the time and function they could have had if access is delayed. Delaying access is not a risk that we should take.
Many issues were identified with the Phase 2 clinical trial and the open-label extension. The benefit was statistically significant and may not be sufficiently persuasive to allow an effectiveness determination based on a single study.
The clinical trial results suggesting that the drug slowed decline on the A.L.S. functional scale were not highly persuasive according to the leader of the F.D.A. team.
The evidence doesn't show that therapy can help patients live longer, according to F.D.A. officials. Patients who received placebo and never switched to AMX0035 survived for a median of 1, 295 days, while patients who received AMX0035 for longer than 96 weeks survived for a median of 1,237 days.
We need to ask ourselves if the survival benefit is due to chance alone or due to underlying disease heterogeneity.
The F.D.A. had concerns about the way the data was analyzed, the way the study accounted for the deaths of patients, and the fact that more patients taking the treatment were taking one of the other A.L. The F.D.A. objected to the trial's method of analyzing data because it did not fit with the company's recommendation.
The director of the F.D.A.'s Office of Neuroscience spoke about the therapy's lack of impact on a biological marker of injury to the brain.
In the interest of having an effective medication available to A.L.S. patients, I think all of us in this space would have preferred to have seen a directional. We think that is a concern in the overall picture.
The F.D.A. agreed with Amylyx that there were no significant safety risks from the therapy. The committee was not asked to vote on the drug's safety.
Dr. Alexander said that it would not be ethical or justified to approve a drug just because it appears safe and desperate patients would be willing to try it.
He said that if you did, we would have dozens of therapies on the market that might not be therapeutic.
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