But on Wednesday, after hours of discussions, several advisers said additional analyzes submitted by the drug’s maker, Cambridge-based Amylyx, strengthened the case for approval, although uncertainty remains. Counselors were also influenced by the severity of the disease and the lack of effective treatments. A promise by a top Amylyx official to pull the drug from the market if a larger study, with 600 patients, fails to show effectiveness was also a factor in the vote.
The FDA, which usually follows the recommendations of its outside advisers but is not required to, is expected to decide whether to approve the drug by September 29.
The improved fortunes of the drug came despite criticism from FDA staff as recently as last week about the treatment’s effectiveness, the conduct of its clinical trial and the researchers’ interpretation of the data.
But the drug is considered safe, and the agency has come under intense pressure from ALS patients and doctors who say the treatment promises a deadly disease that usually causes rapid deterioration and death.
Wednesday’s vote came after a dramatic moment with Billy Dunn, director of the FDA’s Office of Neuroscience, stressing that the agency can use broad flexibility to remove drugs for diseases like ALS that lack effective treatments.
Dunn also noted that the large trial being conducted by the manufacturer will be completed late next year or early 2024; that study is expected to show definitively whether the drug works. In a highly unusual move, he asked company officials if they would voluntarily withdraw the product if it were approved now, but the larger trial failed to show effectiveness.
Justin Klee, CEO of the Cambridge-based biotechnology company, agreed. If the larger trial is not successful, “we will do what is right for patients, which includes pulling the product from the market,” he said.
However, other experts cautioned that a voluntary commitment like Klee’s is not legally binding.
Still, the commitment of Amylyx and its new analysis convinced some panel members to change their votes from March. Liana G. Apostolova, a neurologist at the Indiana University School of Medicine, said the new analyzes made her “mild to moderate” convinced that the drug extends life by at least several months. “Depriving ALS patients of a drug that might work is not something I feel very comfortable with,” she said.
Kenneth Fischbeck, a researcher at the National Institute of Neurological Disorders and Stroke, voted no, as he had done in March. He said he did not believe the drug had met the standard for substantial evidence of effectiveness.
ALS, or amyotrophic lateral sclerosis, destroys nerve cells in the brain and spinal cord. It usually paralyzes patients, robbing them of their ability to walk, talk and eventually breathe. About 30,000 people in the United States have ALS, sometimes called “Lou Gehrig’s disease.” A further 6,000 are diagnosed each year. There are two FDA-approved therapies on the market, but they have limited effectiveness.
The experimental treatment was developed nearly a decade ago by Brown University students who went on to found Amylyx — Klee and Josh Cohen, now co-CEOs.
The ALS drug consists of two components – a prescription drug called sodium phenylbutyrate used to treat rare liver diseases and a dietary supplement called taurursodiol – designed to protect neurons from destruction. The treatment comes in a powder that is dissolved in room temperature water and is drunk or administered through a feeding tube.
Desperate patients want a new ALS drug. The FDA isn’t sure it works.
ALS advocates were delighted with Wednesday’s vote. “We applaud and thank the FDA’s advisory committee for their vote to support approval of AMX0035, and we urge the FDA to expeditiously approve,” said Scott Kauffman, chairman of the ALS Association’s board of directors. “Americans Living with ALS Can’t Wait.”
During the public hearing of Wednesday’s session, leading ALS doctors called for the drug’s approval, saying even small benefits could provide enormous help in managing the deadly neurodegenerative disease. Several patients who have received the drug through clinical trials gave emotional statements and asked for approval.
Vance Burghard said he was diagnosed with ALS in 2017 and soon needed help pulling up his pants. Through a clinical study, he has been on AMX0035 for three years, which he called “life-changing”. He said his condition has stabilized and he has been able to wander in China and Tibet.
Gregory Canter said he participated in the ALS Association’s Ice Bucket Challenge several years ago, even though “I didn’t have ALS and I didn’t know anyone who did.” A few years later, he was diagnosed with the disease and subsequently enrolled in the six-month Amylyx trial. He believes he received a placebo, but as a trial participant was offered the drug after the trial was over, as part of what is called an open study.
Canter said the drug has stabilized his breathing and helped him in other ways. “I am still alive, living independently and the progression of my disease has been noticeably slowed,” he said.
Brian Wallach, a former Obama White House staffer who was diagnosed five years ago, noted that some panel members said they had voted against the drug in March to protect patients from false hope.
“I don’t need you to protect me from myself,” he said. Such “antiquated paternalism is misplaced,” he said through an aide because his speech was heavily affected. “There is only one right answer here. I only hope you have the courage to recommend approval.”
Amylyx applied to the FDA for approval of the drug in November 2021. The company submitted data from a 24-week trial that showed the drug was safe and slowed the decline in essential functions such as walking, talking and cutting food by 25 percent.
In a follow-up study, in which all participants were offered the drug, patients who received the treatment from the start of the study lived a median of more than six months longer than those who did not, the researchers found.
More recent analyzes provided by the manufacturer showed that AMX0035 extended median survival several months longer than originally thought, delayed first hospitalizations and reduced serious complications.
Still, the FDA has signaled for months that it had doubts about approving the drug in a single study, especially when the agency said it didn’t find the data “exceptionally compelling.” The agency said the company did not adequately account for deaths during the trial and took issue with other aspects of the study. It said the additional analyzes did not include new information.
Canada recently approved AMX0035 on a conditional basis. That means Amylyx can sell the drug but is required to confirm its benefits based on the results of the larger study. But the FDA’s approval processes are somewhat different than Canada’s.
Some ALS patients are already taking one or both components of AMX0035. Since sodium phenylbutyrate is approved for another purpose, doctors are allowed to prescribe it off label for ALS. And the supplement, sometimes called TUDCO, is available on a number of websites.
Some health policy experts said in the hearing that the drug should not be approved until further data prove its effectiveness.
Others agreed that the FDA has a legal responsibility to determine that drugs are safe and effective — but noted that it has flexibility in how to do that. Unclear data can complicate the picture.
“Science is messy, and even well-designed trials won’t always give you a clear answer,” said Holly Fernandez Lynch, a University of Pennsylvania bioethicist who is not on the panel.