In a close vote, an advisory panel for the U.S. Food and Drug Administration decided not to recommend the approval of an experimental drug for the deadly neurological disease amyotrophic lateral sclerosis (ALS).
The panel's decision had been closely watched, with patient advocacy groups lobbying hard for fast-track approval.
However, on Wednesday the panel ruled 6-4 that data from a single, mid-stage study sponsored by Amylyx Pharmaceuticals was not enough to prove the company's drug makes a meaningful difference in patients' lives.
"I think it would be a disservice to the patients and their families to approve a treatment that is of uncertain benefit," Dr. Kenneth Fischbeck, of the U.S. National Institutes of Health (NIH), said during the panel meeting, according to the Associated Press. "It gets in the way of developing truly effective treatments if it turns out not to be effective."
Fischbeck and his fellow panelists said they hoped results of a larger study, now underway, would provide more evidence on the drug, known for now as AMX0035.
Even panelists who voted in favor of the drug said the decision was not an easy one.
"I went back and forth during the day, but ultimately I agreed with the [drugmaker's] primary analysis," Dean Follman, a biostatistician with the NIH, told the AP.
Importantly, the vote is not binding and the FDA has until the end of June to make the final call on whether to grant approval of the drug. The panel vote could be seen as confirmation of the agency's own negative review published days prior to the panel meeting. It criticized Amylyx's submitted study for its small size, missing data and questionable statistical analysis.
Still, the FDA has stressed the need for "regulatory flexibility" when weighing drugs for fatal diseases like ALS, which is also known as Lou Gehrig's disease. And the fact that the panel vote was close could tip the agency toward an approval, given the shortage of treatment options for ALS.
Not only that, advocacy groups for patients with ALS have been pushing hard for approval of AMX0035. They say the need is urgent.
Most people with ALS die of respiratory failure within three to five years, according to the NIH. The disease destroys nerve cells needed to walk, talk, swallow and eventually breathe, steadily robbing patients of movement until they're locked inside their own bodies.
AMX0035 is an experimental combination drug that has been shown to extend survival for ALS patients.
Amylyx's request was supported by the ALS Association, one of the main advocacy and research groups devoted to finding a cure for this disease.
"The community has been asking for a long time that the FDA approve the drug before that [phase 3] trial is complete," said Neil Thakur, chief mission officer of the ALS Association. "And the reason why is because of a combination of strong clinical benefit and safety data that we've seen for this this drug."
AMX0035 has been shown in early clinical trials to extend ALS patients' lives by about six and a half months, Thakur said.
The drug also slows disease progression in patients by about 25%, said Dr. James Berry, director of the Massachusetts General Hospital's Neurological Clinical Research Institute in Boston and a principal investigator in the AMX0035 trials.
"ALS is a disease that doesn't give us a lot of time to sort of stop and consider," Berry said. "We really need to move when we see something that looks this promising without a safety concern and with a very well-run study that shows us both survival and function benefit."
AMX0035 is a combination of two established drug ingredients -- sodium phenylbutyrate and taurursodiol.
Sodium phenylbutyrate is sold under the brand name Buphenyl to treat liver diseases, while taurursodiol is a dietary supplement used in ancient Chinese medicine. Some ALS patients already take both drugs. FDA approval would likely compel insurers to cover the treatment.
The drugs are known to affect different aspects of ALS, Berry said.
"The idea was if we took two drugs that sort of fix two different pathways we know are being affected in ALS, they had a chance of having a synergistic effect -- one plus one equals three," Berry said.
Until late last year, the FDA had insisted that Amylyx complete ongoing phase 3 trials before seeking approval for AMX0035.
In December, the agency relented and began a priority review of the drug application, setting June 29 as the target date for a decision.
Phase 2 trials are typically meant to gather safety data and any early signals that would indicate whether a treatment works. Whether a drug actually benefits patients usually isn't established until phase 3 trials. Phase 3 trials involve many more people so the results are more concrete.
The FDA's decision to fast-track consideration of AMX0035 follows its controversial approval of Aduhelm for Alzheimer's patients.
The agency approved Aduhelm under pressure from advocacy groups and the drug's maker, despite mixed clinical trial results and an advisory panel's recommendation against it.
The advisory panel that met Wednesday is the same panel that recommended against Aduhelm. After the FDA overrode its advice, three members resigned in protest.
Some experts are questioning whether the FDA may repeat history with AMX0035, doing further damage to its scientific credibility by again accepting weaker evidence for a drug touted by disease advocates and drugmakers.
"This is what many people were concerned about in terms of the precedent for FDA approving Aduhelm," Dr. Joseph Ross, a professor of medicine and public health at Yale University, told the AP. "They essentially capitulated to both industry and patient advocacy pressure, as opposed to abiding by the science."
But Thakur, of the ALS Association, argues that the situations are completely different between AMX0035 and Aduhelm.
"Alzheimer's is a slow-acting disease and ALS moves really quickly," he said. "I know people want to compare them because they're all neurology drugs, but the diseases are very different."
In a disease like ALS that takes most lives after a handful of years, six months of extended life is significant, Thakur noted.
The ALS Association invested $2.2 million in Amylyx's research, money raised during the Ice Bucket Challenge campaign that went viral online.
As part of that investment, the ALS Association has what Thakur called a "small royalty stake" that could return up to $3.3 million in proceeds if the drug is approved. He said any money earned from AMX0035 would be plowed back into research.
"What we're hoping is that drugs like this that have not a life-changing effect but a life-extending effect can work in combination with other drugs, and we can start to transform the experience of ALS to make it a livable disease," Thakur said.
The U.S. National Institute of Neurological Disorders and Stroke has more about ALS.
SOURCES: Neil Thakur, PhD, chief mission officer, ALS Association, Arlington, Va.; James Berry, MD, MPH, director, Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Associated Press