Cambridge biotech wins approval for much-debated ALS drug

This 2018 photo provided by Amylyx shows the company's cofounders, Joshua Cohen, left, and Justin Klee.Associated Press

The Food and Drug Administration on Thursday approved a controversial new drug for ALS from a Cambridge company, even though agency scientists had questioned whether it would help patients with the devastating disease and a panel of independent medical experts initially recommended it be rejected.

The closely watched drug, called Relyvrio, was developed by Amylyx Pharmaceuticals, a biotech founded in 2013 by two Brown University graduates. In March, an FDA advisory committee cited weak scientific evidence in its recommendation that the agency reject it. But that panel reversed itself on Sept. 7 amid emotional pleas from patients and families affected by the paralyzing and fatal neurological condition, and after Amylyx presented more clinical data that it said showed the medicine extended patients’ lives.

Since 1995, only two drugs have been approved to treat amyotrophic lateral sclerosis ― also known as Lou Gehrig’s disease ― and neither works very well.

“This approval provides another important treatment option for ALS, a rare, life-threatening disease that currently has no cure,” said Dr. Billy Dunn, director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research.

Although a small intermediate-stage study of 137 patients showed the drug extended life by only a few months, Dr. Merit Cudkowicz, chief of neurology at Massachusetts General Hospital and co-principal investigator in the trial, said that is profoundly meaningful to patients.

“I’m beyond thrilled,” she said. “We don’t have any other drugs that slow loss of function and prolong life. Any additional time you give someone living with this illness is a good thing.”

Relyvrio can be taken orally by mixing it with water, or administered through a feeding tube.

Amylyx is conducting a longer, larger trial to confirm the benefits of the medicine, with data expected in late 2023 or early 2024. In an unusual pledge, the company has vowed to remove the drug from the market if that study shows it isn’t successful.

“Amylyx’s goal is that every person who is eligible for Relyvrio will have access as quickly and efficiently as possible, as we know people with ALS and their families have no time to wait,” the company’s co-CEOs, Josh Cohen and Justin Klee, said in a statement.

But some scholars who closely followed the FDA’s approval of several controversial drugs in recent years are concerned the agency is bowing to public pressure to approve medicines with shakier scientific evidence for illnesses without effective treatments.

The U.S. Food and Drug Administration building behind FDA logos at a bus stop on the agency's campus in Silver Spring, Md. on Aug. 2, 2018. Jacquelyn Martin/Associated Press

Since 2016, the agency has approved three drugs developed or partly developed by Massachusetts companies over at least the initial objections of FDA advisers: Exondys 51, for Duchenne muscular dystrophy, from Sarepta Pharmaceuticals; Aduhelm, for Alzheimer’s disease, from Biogen and Eisai; and now the ALS drug.

“We’re actually seeing the FDA pay more attention to patients than it does to its own advisers,” said Dr. Michael Sinha, an assistant professor of health law and pharmaceutical policy at the Saint Louis University School of Law.

Frances Miller, a professor specializing in drug regulation at Boston University School of Law, agreed.

“When you don’t have any other good therapies, the standards get relaxed,” she said. “Are they going forward on the basis of less rigorous evidence than in the past? You betcha.”

ALS is diagnosed in about 6,000 people a year in the United States, according to the Massachusetts chapter of the ALS Association. It affects the nerve cells in the brain and spinal cord, gradually robbing patients of the ability to speak, eat, and, finally, breathe.

Scores of clinical trials of potential ALS treatments have failed over the past decade. Despite the best effort of doctors and researchers,most patients die within three to five years.

Amylyx developed a combination of two molecules ― sodium phenylbutyrate and taurursodiol ― that it believes helps delay the death of nerve cells. The intermediate clinical trial found that the drug prolonged survival by a median of 4.8 months compared with a placebo.

Relyvrio has gone through an unusual regulatory review process during which its fortunes have risen, fallen, and risen again.

In March, the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee, a panel of independent medical experts, voted 6-4 to recommend the FDA reject Amylyx’s application. In what many members described as a difficult decision, the panel concluded that based on the small trial, Amylyx had failed to make a convincing case that the drug was effective.

But this month, the FDA reconvened the advisory panel to hold a second vote after hearing pleas from patients and families and following the presentation of more data. During the second meeting, Amylyx executives said its drug lowered levels of a biomarker in spinal fluid associated with ALS and Alzheimer’s disease. The company also presented new analyses of its clinical data suggesting that its treatment helps people with ALS live up to 11 months longer when compared with historical data about the disease’s progression.

Even so, the FDA said that the biomarker data was not clearly linked to improvements in patients. The agency also seemed unconvinced by the company’s survival analysis, characterizing it as new interpretations of old data.

This image provided by Amylyx Pharmaceuticals shows the drug Relyvrio. Associated Press

Nonetheless, the advisory committee reversed itself and voted 7-2 in favor of the drug.

Amylyx has not disclosed what it will charge here for the medicine.

A Boston-based nonprofit watchdog group, the Institute for Clinical and Economic Review, or ICER, recently said that if the drug were approved, it should be priced at $9,100 to $30,700 based on its clinical benefits to patients, which the organization said ranged from “small to substantial.”

ICER also said that concerns about approving a drug on the basis of a single small trial were legitimate but not a deal breaker.

“For conditions that are rapidly progressive and fatal, considering FDA approval of drugs on the basis of a single trial that shows benefit in clinically meaningful patient-centered outcomes is not unreasonable,” ICER said. “However, there are known risks to approving drugs on the basis of such limited evidence.”

Despite those worries, Phil Green, a 52-year-old former retail marketing executive with ALS who serves as an unpaid adviser to Amylyx on patient issues, was eager for the drug to get approved.

“If this therapy can give us six months to a year or two years, then on the ALS clock that’s a long time because when you’re diagnosed, you don’t have a lot of time,” said Green, who lives in Temecula, Calif., and was diagnosed in 2018.

Marc Litt, a retired cardiologist in Jacksonville, Fla., who was diagnosed with ALS in 2019, said Amylyx published results of its trial in 2020 that were persuasive, but that the FDA “likely caused many patients to worsen” by not clearing the drug sooner.

“Obviously, I realize any treatment won’t cure me now, but if my quality of life can be stabilized, I could enjoy some time with my grandson with what’s left,” he said in an e-mail.

Amylyx consisted of just three people for its first six years as a company. In 2019, it doubled that number, and since announcing positive results from its trial at the end of that year, the firm has raised $370 million from private investors and a public offering. Today the company has about 230 people in the United States, Canada, and Europe, including 100 employees at its main office in Cambridge.