FDA Approves Amylyx’s ALS Therapy

The FDA has approved Amylyx Pharmaceuticals’ AMX0035 — now with the brand name Relyvrio (sodium phenylbutyrate/taurursodiol) — to treat patients with amyotrophic lateral sclerosis (ALS). It is an oral, fixed-dose combination therapy that should be available within four to six weeks, the company said in a call with investors. It will be available through specialty pharmacies, and can be used as a monotherapy or with other therapies.

ALS is a rare disease that attacks and kills the nerve cells that control voluntary muscles. It is a progressive disease, and most cases will result in death from respiratory failure, usually within three to five years from when the symptoms first appear. About 5,000 people in the United States are diagnosed with ALS annually and about 29,000 people are currently living with ALS.

Merit Cudkowicz, M.D.

“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,” Merit Cudkowicz, M.D., co-principal investigator of the CENTAUR trial, said in a press release. “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.”

Cudkowica is co-founder of the Northeast ALS Consortium, chief of Neurology and the director of the Healey & AMG Center for ALS and chief of Neurology at Massachusetts General Hospital, and the Julieanne Dorn Professor of Neurology at Harvard Medical School.

The company formed the Amylyx Care Team, which will provide a single point of contact for patients and help with financial assistance. The wholesale acquisition cost will be $158,000 per year for the first year, which company officials said is below the last approved ALS therapy. Mitsubishi Tanabe Pharma’s Radicava (edaravone), which was approved in 2017, costs about $171,000 a year.

According to an analysis from the Institute for Clinical and Economic Review, the therapy would only achieve traditional thresholds of cost-effectiveness if priced between $9,100 to $30,700 per year.

The company indicated in its investor call that copays for patients in commercial plans will be zero and Relyvrio will be available at no cost to those who are uninsured or underinsured. Patients who participated in clinical trials will have continued access to Relyvrio.

The approval of Relyvrio is based on data from CENTAUR, a multicenter phase 2 clinical trial in 137 participants with ALS encompassing a 6-month randomized, placebo-controlled phase and an open-label extension long-term follow-up phase. The most common adverse events occurring were diarrhea, abdominal pain, nausea, and upper respiratory tract infection. Gastrointestinal-related adverse reactions occurred throughout the study but were more frequent during the first three weeks of treatment.

Related: FDA Advisory Committee Supports Approval of AMX0035 for ALS

Earlier this month, an FDA advisory voted to support approval of the therapy in a 7 to 2 vote, reversing an earlier vote against Relyvrio. At the first advisory committee meeting in March 2022 six of the 10 members voted no on the question of whether the open-label extension of the phase 2 CENTAUR trial established a conclusion that AMX0035 is effective in the treatment of patients with ALS.

Amylyx had submitted additional analysis of survival data from the CENTAUR study and its open-label extension, along with biomarker results from a recently completed phase 2 study of AMX0035 in Alzheimer’s disease. The data in part held to sway several committee members to switch their votes from no to yes.

Research of Relyvrio continues with the phase 3 PHOENIX trial, with results expected in 2024. This trial expects to enroll 600 patients and compare Relyvrio versus placebo. The primary efficacy outcome is the composite measure of survival and Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) total score progression over 48 weeks and survival and tolerability over 48 weeks.

The therapy was also approved in Canada in June with the brand name Albrioza. The company also expects a potential decision from EMA the first half of 2023.