CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Amylyx Pharmaceuticals, Inc. today announced that the first participants have been dosed in the Phase 3 Study A35-004 (PHOENIX) (NCT05021536), a global trial evaluating the safety and efficacy of AMX0035 (sodium phenylbutyrate (PB) and taurursodiol (TURSO; also known as ursodoxicoltaurine)) in people with amyotrophic lateral sclerosis (ALS). The Phase 3 trial will be conducted at approximately 65 sites in Europe and the U.S. in collaboration with TRICALS and NEALS consortia, respectively. The trial will enroll approximately 600 participants with clinically definite or clinically probable ALS within 24 months from symptom onset which expands on the inclusion criteria used in the CENTAUR trial (definite ALS within 18 months of symptom onset).

PHOENIX is a follow-up clinical trial to the CENTAUR trial, which was a placebo-controlled study evaluating 137 people with ALS. In this study, over 24-weeks, participants receiving AMX0035 had statistically significant slowing of functional decline at the end of the 6-month randomized phase as measured by the Revised ALS Functional Rating Scale (ALSFRS-R), the most commonly used scale in clinics worldwide to measure function in ALS. In an interim survival analysis conducted in all randomized participants from CENTAUR who were followed for up to three years, which included participants who continued to receive AMX0035 in an open-label extension phase during the follow-up period, participants who started on AMX0035 during the placebo-controlled phase of CENTAUR showed a 44% lower risk of death compared to those who started on placebo during the placebo-controlled phase (HR 0.56; 95% CI, 0.34-0.92). Median survival duration through the open-label long-term follow-up phase was 25.0 months (95% CI, 19.0-33.6 months) in the group that started on AMX0035 and 18.5 months (95% CI, 13.5-23.2 months) in the group that started on placebo, a 6.5-month difference. Overall, reported rates of adverse events and discontinuations were substantially similar between AMX0035 and placebo groups during the 24-week randomized phase; however, gastrointestinal events occurred with greater frequency (≥2%) in the AMX0035 group. Data from CENTAUR is published in the New England Journal of Medicine(NEJM) and Muscle and Nerve.

“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, M.D., Ph.D., Professor of Neurology at UMC Utrecht in the Netherlands and Chairman of the Treatment Research Initiative to Cure ALS (TRICALS), a large European trial network dedicated to finding a treatment for ALS. “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.”

“ALS is a relentlessly progressive disease with limited treatment options, which means advancements are critical for those living with the disease and their families. I’m enthusiastic about the opportunity to conduct a trial of this size and scope within the Northeast ALS (NEALS) network of trial-ready research centers primarily based in North America, in partnership with TRICALS in Europe, as we continue to evaluate AMX0035 as a potential new therapeutic.” said Sabrina Paganoni, M.D., Ph.D., principal investigator of the CENTAUR study, investigator at the Healey & AMG Center for ALS at Mass General and member of the Executive Committee of NEALS.

The primary efficacy outcome of the 48-week, randomized placebo-controlled PHOENIX Phase 3 trial will be a joint assessment of Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) total score progression over 48 weeks and survival. Secondary efficacy outcomes will include change in slow vital capacity (SVC), measured both at home using a self-administered spirometer to support virtual data collection and at clinic sites using standard spirometry, quality of life patient-reported outcome assessments, ventilation-free survival rates and other measures.

Participants who complete the 48-week study will have the option to receive AMX0035 after the trial if permitted by each regions’ regulatory mechanisms for continued access. This posttrial access to AMX0035 will also be dependent on regulatory and reimbursement milestones.

“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,” said Erin Whitney, B.S., M.B.A., Head of Global Clinical Operations of Amylyx. “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.”

In August, Amylyx announced that Health Canada accepted for review the New Drug Submission (NDS) for AMX0035. More recently, Amylyx announced the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for AMX0035. Amylyx plans to submit a Marketing Authorization Application (MAA) for AMX0035 to the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) by approximately the end of 2021. The company continues to discuss AMX0035 with health authorities around the world and will keep the global ALS community updated. The trial will proceed in parallel with planned marketing authorization submissions in Canada, the United States and the European Union.

Amylyx is currently exploring the possibility for an Expanded Access Program (EAP) in the United States. If implemented, the EAP would run in parallel with the ongoing Phase 3 PHOENIX trial and marketing application reviews. Further information about the EAP is expected in fourth quarter 2021.

About AMX0035
AMX0035 is an investigational product comprised of two complementary active agents, sodium phenylbutyrate (PB) and taurursodiol (TURSO; also known as ursodoxicoltaurine), which were combined in a co-formulation to reduce neuronal death and dysfunction. AMX0035 is designed to target the endoplasmic reticulum and mitochondrial-dependent neuronal degeneration pathways in ALS and other neurodegenerative diseases.

About the PHOENIX Trial
The Phase 3 PHOENIX trial(NCT05021536) is a 48-week, randomized placebo-controlled global clinical trial further evaluating the safety and efficacy of AMX0035 (PB/TURSO) in people with ALS. The primary efficacy outcome of the trial will be a joint assessment of Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) total score progression over 48 weeks and survival. Secondary efficacy outcomes will include change in slow vital capacity (SVC), measured both at home using a self-administered spirometer to support virtual data collection and at clinic sites using standard spirometry, quality of life patient-reported outcome assessments, ventilation-free survival rates and other measures. More information on the PHOENIX trial can be found at www.clinicaltrials.gov, NCT05021536.

About the CENTAUR Trial
CENTAUR was a multicenter clinical trial in 137 participants with ALS encompassing a 6-month randomized placebo-controlled phase and an open-label long-term follow-up phase. The trial met its primary efficacy endpoint of slowing functional decline as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R).

Overall, reported rates of adverse events and discontinuations were substantially similar between AMX0035 and placebo groups during the 24-week randomized phase; however, gastrointestinal events occurred with greater frequency (≥2%) in the AMX0035 group.

In an interim survival analysis conducted in all randomized participants from CENTAUR who were followed for up to three years, which included participants who continued to receive AMX0035 in an open-label extension phase during the follow-up period, participants who started on AMX0035 during the placebo-controlled phase of CENTAUR showed a 44% lower risk of death compared to those who started on placebo during the placebo-controlled phase (HR 0.56; 95% Confidence Interval (CI), 0.34-0.92). Median survival duration through the open-label long-term follow-up phase was 25.0 months (95% CI, 19.0-33.6 months) in the group that started on AMX0035 and 18.5 months (95% CI, 13.5-23.2 months) in the group that started on placebo, a 6.5-month difference.

The CENTAUR trial was funded, in part, by the ALS ACT grant and the ALS Ice Bucket Challenge, and was supported by The ALS Association, ALS Finding a Cure® (a program of The Leandro P. Rizzuto Foundation), the Northeast ALS Consortium, and the Sean M. Healey & AMG Center for ALS at Mass General.

More information on the CENTAUR trial can be found at https://www.amylyx.com/pipeline/ or www.clinicaltrials.gov, NCT03127514 or NCT03488524.

About Amylyx Pharmaceuticals
Amylyx Pharmaceuticals, Inc. is a pharmaceutical company working on developing a novel therapeutic for amyotrophic lateral sclerosis (ALS), Alzheimer’s disease and other neurodegenerative diseases. For more information, visit www.amylyx.com and follow us on LinkedIn and Twitter.