- Federal regulators have approved the drug Relyvrio for the treatment of amyotrophic lateral sclerosis (ALS).
- An advisory panel had recommended approval of the drug in early September after expressing concerns earlier this year.
- People with ALS as well as their families and patient advocates have been lobbying for approval of the drug.
The Food and Drug Administration (FDA) has approved a new oral drug to treat amyotrophic lateral sclerosis, or ALS, a nervous system disease that weakens muscles.
The medication has been criticized by an FDA panel, although that group of advisors voted in early September to recommend approval after reviewing updated clinical trial data.
Other experts have expressed concerns over the drug’s effectiveness while members of the ALS community have strongly urged it be approved.
“This approval provides another important treatment option for ALS, a life-threatening disease that currently has no cure,” said Dr. Billy Dunn, the director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, in a statement. “The FDA remains committed to facilitating the development of additional ALS treatments.”
The drug, formerly known as AMX0035, will be sold under the brand Relyvrio.
Relyvrio can be taken orally by combining one packet with 8 ounces of room temperature water. It can also be administered through a feeding tube.
Amylyx Pharmaceuticals, the company that makes Relyvrio, asked the FDA earlier this year to consider approving the drug before its phase 3 clinical trial was completed.
“What we saw in our first major clinical trial is that the drug was found to be quite safe. People maintained their function longer and people lived longer,” said Justin Klee, the co-chief executive officer and co-founder of Amylyx.
“It’s the first time we’ve seen that in ALS and given that ALS is so relentlessly progressive and universally fatal, the fact that the drug showed both an effect on function and on survival is really exciting,” he told Healthline.
There are five other drugs also approved to treat ALS, which is also known as Lou Gehrig’s Disease.
Long, winding road
In March, the FDA advisory committee initially voted on whether they considered AMX0035 to be effective in treating ALS.
The panel of independent advisors said the drug appeared to be safe and well-tolerated. However, the majority of the advisors did not believe the data from the company’s CENTAUR or phase 2 clinical trial showed that the drug was effective in treating ALS.
In a rare second hearing in early September, the FDA advisors expressed concerns again about the drug’s effectiveness but still voted 7-2 to recommend approval.
The FDA wasn’t bound by the advisory committee’s recommendations. Agency officials originally said they would issue a decision on its priority review of AMX0035 by late June. But the agency pushed back that deadline by 90 days, saying it needed more time to look at additional information.
Health Canada has approved the drug for use in that country with several conditions. Amylyx has to provide data from its now ongoing phase 3 PHOENIX clinical trial and any other planned or ongoing studies. The results from that phase 3 trial are not expected until 2024.
Lobbying the FDA
For months, advocates have lobbied the FDA to approve the drug before the phase 3 trial ended.
Thousands of people with ALS and their family members have emailed the agency urging approval of AMX0035 through a campaign organized by The ALS Association.
In May, a group of 38 doctors and scientists signed off on a letter to the FDA also urging the agency to approve the drug. The clinicians cited the short life expectancy of people with ALS and that many would die waiting for the results of a phase 3 clinical trial.
“I had a patient die (in June). He had been hoping to participate in an expanded access program,” said Dr. Jinsy Andrews, a professor of neurology at Columbia University in New York.
“There are people who just want access to new drugs because they’ve exhausted all other options… and they’re not going to survive until the end of another study,” she told Healthline.
“It’s important because we haven’t had many successes in ALS” she added. “As these applications are coming in and challenging how we look at the clinical trial data, it’s pushing our field as a whole to think about what’s our minimum level of evidence to have access to a therapy.”
“The FDA has a relatively high standard, which I think is a valid perspective,” said Dr. Robert Kalb, a professor of neurology at the Northwestern University Feinberg School of Medicine in Chicago, Illinois.
“It’s a difficult position to try and adjudicate between their standards of being responsible stewards and making sure that actually these compounds are effective, versus the need to get stuff out to patients as soon as possible,” he told Healthline.
“I would say the effectiveness of these compounds is pretty much similar to lots of other compounds that we’ve studied in mouse models of ALS over the years,” he explained.
“If there was a certain cell population of patients that the AMX0035 compound works in, Hallelujah. I mean nothing would make me happier. I’m not down on it, I just don’t have enough information” he said. “But my gut, based on what I’ve seen and based on the quality of the investigators involved, suggests to me that it’s likely to be an effective therapy.”
Relyvrio is a compound of two drugs.
One is sodium phenylbutyrate, which is prescribed to treat a metabolic defect involved in helping to remove ammonia from the body.
The other is taurursodiol, also known as TUDCA, often sold in health food stores. It is marketed as a way to help “detoxify” the liver.
Doctors say the delay in the approval of Relyvrio had patients and their families desperately trying to get the individual drugs.
“Some of the ingredients, although not the same as the actual investigational drug, can be purchased either over the counter or through off-label prescription. It created shortages for the suppliers, especially in my region,” said Andrews.
“I have patients who asked for sodium phenylbutyrate. I’m happy to write a prescription, but the cost is outrageous. And they may have to try and find it in other markets, like Europe,” Kalb said.
Meanwhile, patients and practitioners keep hoping for a solution.
“As we continue to have a more sophisticated and nuanced view of what ALS really is, we will have more targeted therapies,” Kalb said.