Cambridge biotech wins approval for controversial ALS drug

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

“This approval provides another important treatment option for amyotrophic lateral sclerosis, a rare, life-threatening disease for which there is currently 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, medium-stage study in 137 patients showed the drug extends life by just a few months, Dr. Merritt Kodkovic, chief of neurology at Massachusetts General Hospital and co-principal investigator on the trial, said it has profound meaning for patients.

“I am very excited,” she said. We don’t have any other drugs that slow loss of function and extend life. Any extra time you give someone with this disease is a good thing.”

Relivrio can be taken orally by mixing With water, or through a feeding tube.

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

“Amylyx’s goal is that everyone who qualifies for Relyvrio will be able to access as quickly and efficiently as possible, as we know people with ALS and their families don’t have time to wait,” he said in a statement.

But some scientists who have closely followed the Food and Drug Administration’s approval of several controversial drugs in recent years worry that the agency is yielding to public pressure to approve drugs with the most shaky scientific evidence. For diseases without effective treatments.

Since 2016, the agency has approved three drugs developed by Massachusetts companies or developed in part due to at least initial objections from FDA advisors: Exondys 51, for Duchenne muscular dystrophy, from Sarepta Pharmaceuticals; Aduhelm, for Alzheimer’s disease, from Biogen and Eisai; And now ALS.

“We actually see the FDA paying more attention to patients than it does to its advisors,” said Dr. Michael Sinha, associate professor of health law and pharmaceutical policy at Saint Louis University School of Law.

Frances Miller, a professor of drug regulation at Boston University School of Law, agrees.

“When you don’t have any other good treatments, the standards are relaxed,” she said. “Are they moving forward on less rigorous evidence than in the past? I bet.”

About 6,000 people are diagnosed with amyotrophic lateral sclerosis annually in the United States, according to the Massachusetts chapter of the ALS Association. It affects nerve cells in the brain and spinal cord, gradually robbing patients of the ability to speak, eat, and eventually breathe.

Dozens of clinical trials of potential amyotrophic lateral sclerosis treatments have failed over the past decade. Despite the best efforts of doctors and researchers, most patients die within three to five years.

Amylyx has developed a combination of two molecules – sodium phenylbutyrate and taurursodiol – that are believed to help delay nerve cell death. The median clinical trial found that the drug extended survival by an average of 4.8 months compared to a placebo.

Relyvrio went through an extraordinary regulatory review process during which its fortunes rose, fell and then rose again.

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

But this month, the Food and Drug Administration (FDA) reconvened the advisory panel for a second vote after hearing pleas from patients and their families and after providing more data. During the second meeting, Amylyx executives said its drug lowered levels of biomarkers in spinal fluid linked to ALS and Alzheimer’s disease. The company also presented new analyzes of its clinical data indicating that its treatment helps people with ALS live up to 11 months longer when compared to historical data on disease progression.

even so, The FDA said vital sign data was not clearly associated with improvements in patients. The agency also seemed unconvinced by the company’s survival analysis, calling it new interpretations of old data.

However, the advisory committee reversed itself and voted 7-2 in favor of the property.

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

The Boston-based nonprofit monitoring group, the Institute for Clinical and Economic Review, or ICER, recently said that if the drug is approved, it should be priced between $9,100 to $30,700 based on its clinical benefits to patients, which the organization said range from $9,100 to $30,700. Small to large.

ICER also said concerns about approving a drug based on one small trial are legitimate but don’t spoil the deal.

“For cases that progress rapidly and fatally, considering FDA approval of drugs on the basis of a single trial showing benefit in clinically meaningful patient-centered outcomes is unreasonable,” ICER said. “However, there are known risks to drug approval based on this limited evidence.”

Despite those concerns, Phil Green, a 52-year-old former retail marketing executive who works as an unpaid consultant to Amylyx on patient issues, was eager to get approval for the drug.

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

Mark Lett, a retired cardiologist in Jacksonville, Florida, who was diagnosed with amyotrophic lateral sclerosis in 2019, said Amylyx published the results of its trial in 2020 that were convincing, but the FDA “likely exacerbated the condition of many patients” by not removing the drug. sooner.

“Obviously I realize that no treatment will cure me now, but if my quality of life can be stabilized, I can enjoy some time with my grandson with what’s left,” he said in an email.

Amylyx consisted of only three people during 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 company has raised $370 million from private investors and a public offering. Today the company has about 230 people in the US, Canada and Europe, including 100 employees at its head office in Cambridge.


Jonathan Saltzman can be reached at jonathan.saltzman@globe.com. Ryan Cross can be reached at ryan.cross@globe.com. Follow him on Twitter Tweet embed.

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