Relyvrio (AMX0035) Approved in US for ALS Treatment

FDA approves Amylyx Pharmaceuticals' twice-a-day medication

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Note: This story was updated Sept. 30, 2022, to correct the spelling of Albrioza and clarify the FDA advisory committee voted in March that the evidence from CENTAUR was not sufficient to support Relyvrio’s efficacy in ALS. It also added Relyvrio’s list price is set at about $158,000 per year.

The U.S. Food and Drug Administration (FDA) has approved Amylyx Pharmaceuticals‘ Relyvrio (sodium phenylbutyrate and taurursodiol), formerly known as AMX0035, for the treatment of adults with amyotrophic lateral sclerosis (ALS).

The decision follows an FDA advisory committee meeting, held earlier this month, in which experts reversed their previous opinion and voted in favor of Relyvrio, noting evidence was sufficient to support an approval.

A conditional approval also was granted recently in Canada, where the medication is sold under the brand name Albrioza. AMX0035 is under regulatory review in Europe.

“Today’s FDA approval of Relyvrio is an exciting milestone for the ALS community and is a major step toward achieving our mission to one day end the suffering caused by neurodegenerative diseases,” Joshua Cohen and Justin Klee, co-CEOs of Amylyx, said in a company press release.

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“We want to give a heartfelt thank you to the broader ALS community, including healthcare professionals and those living with ALS, for their guidance, support of our clinical programs, and for sharing their experiences with us,” added Cohen and Klee. “Their stories inspired us and helped our team to better understand the ALS clock, instilling in us a deep sense of urgency that will continue to drive us forward. This is just the beginning and there is much more to be done.”

Relyvrio can be taken alone and in combination with existing ALS treatments. According to Amylyx, physicians in the U.S. can start prescribing the medication to their patients immediately, and shipping is expected to start in the next four to six weeks.

“Our priority now is to ensure that adults living with ALS in the U.S. whose doctors have prescribed Relyvrion can access it as quickly as possible,” said Margaret Olinger, global head of commercial and chief commercial officer of Amylyx.

Given twice daily by mouth or via feeding tube, Relyvrio is a fixed-dose combination of two compounds in clinical use — tauroursodeoxycholic acid and sodium phenylbutyrate — that are thought to protect nerve cells from forms of cellular stress that drive ALS progression.

The CENTAUR trial

Amylyx’s applications for approval were supported by data from the CENTAUR Phase 2 clinical trial (NCT03127514), which evaluated Relyvrio in 137 adults who had been recently diagnosed with ALS and whose disease was progressing rapidly.

Participants were assigned randomly to receive oral Relyvrio or a placebo, twice daily for 24 weeks (about six months). At the end of CENTAUR, most patients entered an open-label extension study (NCT03488524) in which all received Relyvrio for up to 2.5 years.

Top-line data showed CENTAUR met its main goal, with Relyvrio-treated patients experiencing a significantly slower functional decline on the ALS Functional Rating Scale-Revised over the six months than those given a placebo (mean monthly loss of 1.24 points vs. 1.66 points with a placebo).

The Relyvrio group also showed a trend toward slower declines in muscle strength and lung function and fewer hospitalizations, but only changes in upper limb strength were significantly different from those in placebo.

Additional data spanning CENTAUR and its extension study also showed survival was extended by a mean of 6.9 months among patients who were initially assigned Relyvrio, compared with those who began treatment only in the extension part of the trial. The findings represented a 43% lower risk of death among those who started treatment early.

After the data was submitted to the FDA, an advisory committee voted 6-4 that there was not enough substantial evidence to support Relyvrio’s efficacy, noting concerns about CENTAUR, including its small number of patients, missing data, and questionable statistics.

While the FDA’s final decision was first expected on June 29, the regulatory agency postponed its decision by three months to enable the review of new data submitted by Amylyx, which the FDA considered to be major amendments to the application.

Decision to delay criticized

The delay was met with criticism from the ALS community, particularly in light of the therapy’s Canadian approval in June. On June 29, the original expected decision date, leading ALS organizations in the U.S. signed a joint letter urging the regulatory agency to act sooner, given the urgent need for new and effective treatments.

The FDA advisory committee met again earlier this month to review the additional trial data, including an analysis that suggested Relyvrio extended the median survival time by more than 10 months compared with estimated survival if patients had been on a placebo for the entire trial. In a rare reversal, the committee voted 7-2 in favor of Relyvrio.

“Our organizations have been on a mission to create a world free of ALS,” leading ALS organizations including The ALS Association, Answer ALS Foundation, I AM ALS, Les Turner ALS Foundation, and Team Gleason, stated in a joint statement Thursday.

“With today’s approval, we are encouraged that Relyvrio can offer people living with ALS and their families the potential of more time with functional independence. This is especially important for a rapidly progressive disease with a median survival time from diagnosis of just two to three years,” they added. “This is significant for people living with ALS, their loved ones, caregivers, clinicians, researchers, and advocacy, as we now have a new treatment option that could be a big step forward for the future of ALS care.”

After gathering input from patients and experts in the ALS community, Amylyx announced in a conference call it has set Relyvrio’s price at about $158,000 per year. This is below the annual cost of Radicava (edaravone), the latest FDA-approved ALS treatment that is priced at about $169,000 per year.

The company also will provide support to physicians wishing to prescribe Relyvrio and to patients who have been prescribed the medication via its Amylyx Care Team (ACT) Support Program. The program will help patients and their families navigate through their treatment journey, from insurance coverage, to financial assistance, to education and resources about Relyvrio treatment.

“The approval of a new treatment that helps slow the progression of ALS, preserve physical function and potentially extend survival has the potential to greatly impact the hundreds of people living with ALS who I currently treat,” said Merit Cudkowicz, MD, co-principal investigator of the CENTAUR trial and director of the Healey & AMG Center for ALS in Massachusetts.

“There are too few options to target this uniformly fatal and rapid illness, and I am encouraged at this outcome and what it represents for my patients and their families,” added Cudkowicz, who also is chief of neurology at Massachusetts General Hospital, and the Julieanne Dorn Distinguished Professor of Neurology at Harvard Medical School.

Amylyx is now running a Phase 3 trial, called PHOENIX (NCT05021536), to confirm Relyvrio’s safety and efficacy in a larger group of patients. Up to 600 adults with ALS, whose symptoms emerged in the past two years, are being enrolled at dozens of sites across the U.S. and Europe. The trial is expected to conclude in early 2024.