Dosing Begins in Phase 3 PHOENIX Trial of AMX0035
The PHOENIX trial (NCT05021536) is expected to include 600 participants whose symptoms began in the past two years, which is a less-stringent criteria than was required for the smaller CENTAUR Phase 2 trial (NCT03127514).
Enrollment will run across 65 clinical sites in the U.S. and Europe, as part of collaborations with the Northeast ALS Consortium (NEALS) and the Treatment Research Initiative to Cure ALS (TRICALS), respectively. More information on enrollment will be available at the trial’s webpage.
“We’re grateful for the opportunity to work with TRICALS and NEALS, two of the largest ALS research organizations in the world, on a trial of this scale. Collaborating with both groups gives us the best opportunity to quickly and efficiently recruit and advance this study and enable us to learn more about AMX0035,” Erin Whitney, head of Global Clinical Operations of Amylyx, said in a press release.
AMX0035 is a fixed-dose combination of two small molecules, tauroursodeoxycholic acid and sodium phenylbutyrate, that have been used in the clinic and are proven to be safe and well-tolerated.
Together, they prevent nerve cell death by blocking stress signals within mitochondria — the cells’ powerhouses — and the endoplasmic reticulum, a cellular organelle involved in protein production, modification, and transport.
The CENTAUR trial investigated the effectiveness and safety of AMX0035 treatment over six months against a placebo in 137 adults recently diagnosed with ALS and whose disease was progressing rapidly.
After showing that AMX0035 significantly slowed functional decline and extended survival, compared with a placebo, Amylyx submitted applications to Health Canada and announced plans to ask the European Medicines Agency for approval by the end of the year.
In an initial decision, the U.S. Food and Drug Administration had said it would require data from an additional controlled clinical trial – the PHOENIX trial – before considering AMX0035 for approval. However, after more recent discussions with the regulatory agency, Amylyx announced it would submit an application based on CENTAUR data alone, which it did earlier this month.
The recently initiated PHOENIX trial will include 600 participants who will be assigned randomly to a placebo or AMX0035 for 48 weeks (about 11 months). Patients then will have the option to receive this treatment following the trial, depending on regional guidelines, regulatory, and reimbursement milestones.
The trial’s primary goal is to assess changes in a joint assessment of functional decline, measured with the ALS Functional Rating Scale-Revised (ALSFRS-R), and survival. Secondary measures include changes in lung function, the need for ventilation, and quality of life.
“Given the results from CENTAUR, it is especially important that we advance the scientific understanding of ALS and continue investigating AMX0035 for the hundreds of thousands of people living with the disease worldwide,” said Leonard H. van den Berg, MD, PhD, chairman of TRICALS. “We’re looking forward to collaborating on the Phase 3 PHOENIX study with NEALS as it will take a global and unified effort to make promising advances for patients and their families.”
“We are excited by the potential of these data to add to our growing body of evidence for AMX0035 in ALS and for this study to provide an opportunity for access to AMX0035 to those living with ALS in the United States and Europe,” Whitney added.
Amylyx also is considering an expanded access program (EAP) to provide AMX0035 to ALS patients in the U.S. before its potential approval. If approved, the program will run in parallel with the application review and the PHOENIX trial. More information about the EAP is expected by the end of the year.