Global Phase 3 Trial of AMX0035 to Enroll 600 ALS Patients, Amylyx Says

A global Phase 3 trial of AMX0035 as an oral treatment for amyotrophic lateral sclerosis (ALS)  intends to enroll up to 600 patients, the therapy’s developer, Amylyx Pharmaceuticals, announced in a press release.

Likely to begin in the coming months, the trial — to be called PHOENIX — will take place at 55 sites across the U.S. and Europe, the result of a collaboration between the Northeast ALS Consortium (NEALS) and the Treatment Research Initiative to Cure ALS (TRICALS).

“It is our hope that findings from PHOENIX will build upon compelling results from CENTAUR,” said Joshua Cohen, Amylyx’s chairman, co-CEO, and co-founder. “We look forward to continued collaboration with study investigators in Europe and the U.S., advocacy groups, and the ALS community as we seek to advance AMX0035 through the clinical development and regulatory review process.”

AMX0035 is made of two small molecules, tauroursodeoxycholic acid and sodium phenylbutyrate, that protect nerve cells. Both compounds are in clinical use, and known to be generally safe and well tolerated. They work to block stress signals within mitochondria — the powerhouses of cells — and the endoplasmic reticulum, a cellular organelle involved in protein production, modification, and transport.

Top-line results from CENTAUR (NCT03127514), a Phase 2/3 study, showed treatment with AMX0035 slowed functional decline and significantly extended life in 137 patients with rapidly progressing disease. The U.S. Food and Drug Administration (FDA), however, requested an additional placebo-controlled trial to consider AMX0035 for approval.

Results of the PHOENIX study are expected to support an approval application to the U.S. agency.

Its design was recently discussed at the virtual European Network to Cure ALS (ENCALS) meeting 2021, held May 12–14, in the presentation “Design of the International, Randomized, Placebo-Controlled Phase 3 PHOENIX Trial of AMX0035 in Amyotrophic Lateral Sclerosis.”

PHOENIX aims to enroll patients whose symptoms began in the past two years — a less-stringent criteria than was required for CENTAUR.

Participants will be assigned randomly to AMX0035 or to a placebo for 48 weeks (about 11 months), after which they may continue or start using this treatment, according to regional guidelines.

Its main goal is changes from the study’s start in functional decline, measured using the ALS Functional Rating Scale-Revised (ALSFRS-R), and in survival. Secondary goals include changes in lung function, evaluated both at the testing site and at a patient’s home, the need for ventilation, and patient-reported outcomes.

“The PHOENIX trial builds on the success of the CENTAUR trial,” Sabrina Paganoni, MD, PhD, CENTAUR’s principal investigator, said in the release. “I strongly believe in global collaboration … and we look forward to advancing this research and what it might mean for those living with ALS.”

Participants in CENTAUR were assigned to either AMX0035 or a placebo twice daily for 24 weeks (about six months). They then were invited to enter an open-label extension (NCT03488524), in which all were given the therapy for up to 30 months.

In addition to top-line results finding that AMX0035 slowed disease progression (measured using the ALSFRS-R) independently of other medication use or duration, patients randomized to treatment also were significantly less likely to be hospitalized or to need permanent ventilation or tracheostomy.

Amylyx has said it plans to request  AMX0035’s approval in the European Union and Canada based on CENTAUR results.

The ALS Association and I AM ALS filed a petition with the FDA in November, signed by more than 50,000 patients, caregivers and family members, asking the FDA to approve AMX0035 based on CENTAUR results.