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Amylyx ALS drug fails crucial study, putting company’s future in doubt

A large clinical trial meant to confirm the benefits of a new ALS medication has instead failed, dealing a major blow to the therapy’s developer as well as patients who had hung their hopes on it.

Amylyx Pharmaceuticals disclosed Friday morning that the drug, known as Relyvrio in the U.S., didn’t meet the trial’s main or secondary goals. Though well-tolerated by participants, Relyvrio was not significantly better than a placebo at changing the trajectory of their disease.

For Amylyx, the results are a monumental setback. The Massachusetts-based biotechnology company was built entirely around Relyvrio, which received approval from the Food and Drug Administration in the fall of 2022. Early sales made Amylyx profitable – a rare victory for any young drugmaker. Some Wall Street analysts have estimated Relyvrio could bring in $1 billion or more per year at its peak.

Now, the company’s future is unclear. Before Relyvrio’s approval, Amylyx co-founders Justin Klee and Joshua Cohen pledged, at the request of a top FDA official, to pull their drug from the market should confirmatory testing fail.

In a statement, Amylyx said that sometime in the next eight weeks, it will share its plans for Relyvrio, which “may include voluntarily withdrawing [the drug] from the market.” The company also intends to discuss the new results with regulators, doctors and the broader amyotrophic lateral sclerosis community.

In the meantime, Amylyx will pause promoting the product.

“Our main priority at the moment is sharing the information with people living with ALS and their treating physicians,” said Klee and Cohen, who also serve as the company’s co-CEOs.

“We will be led in our decisions by two key principles: doing what is right for people living with ALS, informed by regulatory authorities and the ALS community, and by what the science tells us,” they added.

By the end of September, nearly 4,000 of the roughly 30,000 ALS patients in the U.S. were on Relyvrio, according to Amylyx’s estimates. The drug is also available in Canada, where it’s sold under the brand name Albrioza. Amylyx attempted to secure approval in the European Union, too, but wasn’t successful, as regulators there had concerns about the treatment’s overall effectiveness and the reliability of the supporting data.

In the U.S., Relyvrio was approved based on data from a 137-person trial codenamed CENTAUR. The study, results from which were published in The New England Journal of Medicine, found essential functions like walking, talking, eating and breathing declined a bit slower in participants given Amylyx’s drug as opposed to a placebo.

Relyvrio-treated patients also lived a median of five months longer than those in the control arm.

Initially, the FDA wanted Amylyx to run another, larger study before submitting its drug for review. But after receiving intense backlash from ALS patients and advocates, who have pressed regulators to be more flexible in evaluating potential treatments, the agency backtracked. Amylyx was allowed to apply for approval while simultaneously running that additional trial.

Still, the FDA had reservations. In the spring and summer of 2022, the agency took a highly unusual step and twice convened meetings to ask outside experts about Relyvrio’s merits. In those meetings, FDA staff were critical of the ways Amylyx interpreted data from CENTAUR.

Yet, with few other medicines available to ALS patients, the FDA ultimately chose to rubber stamp Relyvrio despite warnings from some of its advisers. “We essentially have a single study with many non-trivial scientific concerns,” said G. Caleb Alexander, an internist and epidemiologist at the Johns Hopkins Bloomberg School of Public Health, during one of the meetings.

Alexander, along with other experts, has also been skeptical that Amylyx’s founders would actually follow through with their pledge to withdraw Relyvrio. “The FDA, with all due respect, significantly understates the complexity and likelihood of their pulling a product from the market,” he said.

If Amylyx does pull its drug, ALS patients in the U.S. would be left with just three other approved therapies. One, from Biogen, is for a very small portion of the population with certain genetic mutations. The other two, called Radicava and riluzole, have shown modest effects on either function or survival.

Amylyx’s share price plummeted more than 75% in pre-market trading Friday, wiping nearly $1 billion from the company’s market value.

Amylyx has been testing Relyvrio as a potential treatment for two more rare conditions – Wolfram syndrome and progressive supranuclear palsy – and said those studies will continue.

On a Friday morning call with Amylyx leadership, analysts questioned how long the company, which had $371 million in cash by the end of last year, can survive.

“I think it’s important for investors to get a view of whether the company does still have a viable future,” said Mizuho Securities analyst Graig Suvannavejh. “Is there any current view around perhaps even looking beyond what you have now … to add other things that further diversify the company?”

Klee noted that Amylyx has a “strong conviction” in its earlier programs. And according to Chief Financial Officer James Frates, the company has enough cash to focus on those programs, just “under a very different structure.”

“If we’re in the worst-case scenario, we’ll take swift action,” Frates said. “And we’ll be very focused on what the business looks like going forward.”