Relyvrio withdrawn from US, Canada after Phase 3 trial results

ALS disease progression rates were similar to standard treatment

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by Steve Bryson, PhD |

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Relyvrio (sodium phenylbutyrate and taurursodiol), an approved treatment for amyotrophic lateral sclerosis (ALS), was voluntarily removed from the U.S. and Canadian markets.

Amylyx Pharmaceuticals, the therapy’s developer, made the decision after top-line results from the Phase 3 PHOENIX trial (NCT05021536) showed that patients who received Relyvrio as an add-on to standard ALS medications experienced a similar rate of disease progression as those given a standard treatment alone.

As of April 4, Relyvrio is no longer available for new patients. Patients receiving the therapy in the U.S. and in Canada, where it was marketed under the brand name Albrioza, who want to continue on treatment can transition to a free drug program after consulting with their physicians.

“While this is a difficult moment for the ALS community, we reached this path forward in partnership with the stakeholders who will be impacted and in line with our steadfast commitment to people living with ALS and other neurodegenerative diseases,” said Joshua Cohen and Justin Klee, co-CEOs of Amylyx, in a company press release.

“The decision to remove Relyvrio/Albrioza from the market and provide therapy free of charge for those who wish to continue was informed by the PHOENIX trial results, engagement with regulatory authorities, and discussions with the ALS community,” Cohen and Klee said. “Thank you to each and every person who shared feedback with us and continues to support our commitment to the ALS community.”

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Phase 2 results suggested slowing of functional decline

Relyvrio, formerly known as AMX0035, was approved in the U.S. and Canada in 2022 based on data from the Phase 2 CENTAUR study (NCT03127514). The study enrolled 137 adults with recently diagnosed, rapidly progressing ALS.

After six months, there was significantly less decline in physical function, as assessed by the ALS Functional Rating Scale-Revised (ALSFRS-R), among adults given Relyvrio than those on a placebo. Data also suggested the therapy may extend survival.

Still, an advisory committee with the U.S. Food and Drug Administration initially voted there was not enough substantial evidence to support Relyvrio’s efficacy, and European authorities also recommended against approval based on these data alone.

Although the treatment was ultimately approved in the U.S. based on the early data, the company said it would consider withdrawing the marketing application if Relyvrio failed to prove beneficial in a confirmatory Phase 3 trial.

The PHOENIX trial was launched to confirm Relyvrio’s effectiveness over one year, enrolling 664 people with early ALS. However, top-line data showed the trial failed to meet its primary goal of slowing the decline in ALSFRS-R scores compared with a placebo. These results were a key factor in the decision to remove Relyvrio from the market.

Top-line PHOENIX data will be presented at the American Academy of Neurology (AAN) annual meeting this month and will be available on Amylyx’s website following the presentation.

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PHOENIX results to inform future research

The company will evaluate and share PHOENIX’s findings to help inform future ALS research and collect survival data at the encouragement of ALS specialists. The PHOENIX open-label extension study (NCT05619783) in Europe is ongoing.

Relyvrio also is being evaluated as a potential treatment for other neurodegenerative conditions, including Wolfram syndrome and progressive supranuclear palsy.

Amylyx will continue to advance its experimental ALS treatment AMX0114, which targets calpain-2, a protein involved in nerve fiber degeneration. In preclinical studies, AMX0114 achieved a dose-dependent reduction of calpain-2 protein levels in human motor neurons, the nerve cells affected in ALS. The company expects to launch a clinical trial to test AMX0114 in ALS later this year.

“We also remain focused on ALS and believe AMX0114 has strong potential for the treatment of ALS and other diseases,” said Camille L. Bedrosian, MD, chief medical officer of Amylyx. “Calpain-2 is considered an essential protein in the process of axonal degeneration.”

“In our preclinical studies of AMX0114 and in multiple independent published studies, inhibition of calpain-2 has reduced cell death and degeneration,” Bedrosian said. “We expect to initiate a clinical trial studying AMX0114 in ALS in the second half of this year.”