- Administration of AMX0035 Is Associated with a Statistically Significant Retention of Functional Abilities and Long-Term Survival Benefit in People Living with ALS

- New Analysis Using ENCALS Survival Prediction Model Demonstrates Longer Overall Survival Resulting from AMX0035 Use Compared to Predicted

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Amylyx Pharmaceuticals, Inc., a pharmaceutical company focused on developing new treatments for amyotrophic lateral sclerosis (ALS), Alzheimer’s disease and other neurodegenerative diseases, today announced the presentation of results from the CENTAUR and open-label extension (OLE) trials demonstrating positive results from administration of AMX0035 in the retention of functional abilities and survival for people with ALS at the 31st International Symposium on ALS/MND.

CENTAUR was a 24-week placebo-controlled study of 137 participants with ALS that evaluated the safety and efficacy of AMX0035. The study was led by Drs. Sabrina Paganoni and Merit Cudkowicz from the Healey Center for ALS at Mass General in collaboration with the Northeast ALS Consortium. As previously reported, the study met its primary efficacy endpoint of slowing ALS as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R). Similar rates of adverse events were seen in the AMX0035 and placebo arms.

An overall survival analysis from CENTAUR followed each participant for up to three years from the start of the trial regardless of whether or not they continued in the OLE part of CENTAUR. The analysis found that the group of participants randomized to AMX0035 at baseline had a 44% lower risk of death compared to the group who originally received placebo over the duration of follow-up (HR, 0.56; 95% CI, 0.34–0.92; P=0.023).

“We are pleased to share detailed findings from CENTAUR demonstrating the positive results on function and survival from AMX0035 for people living with ALS,” said Sabrina Paganoni, M.D., Ph.D., principal investigator of the CENTAUR trial, investigator at the Sean M. Healey & AMG Center for ALS at Mass General and Assistant Professor of PM&R at Harvard Medical School and Spaulding Rehabilitation Hospital. “In addition, we are presenting new results from an analysis using the ENCALS survival prediction model. Use of this model has increased our understanding of AMX0035’s impact on survival and may be an invaluable tool for ALS clinicians and future trial designs.”

In collaboration with TRICALS ALS researchers at UMC Utrecht in the Netherlands, including Leonard van den Berg, M.D., Ph.D., Henk-Jan Westeneng, M.D. and Ruben van Eijk, M.D., Ph.D., an analysis using the ENCALS survival prediction model was performed to produce survival predictions for individual participants in CENTAUR. These predictions were used to compare actual survival vs. predicted survival in CENTAUR which enrolled a fast-progressing patient population.

Key Results from ENCALS Survival Prediction Model Analysis:

  • AMX0035 and placebo groups were well-matched and had a similar prognosis at baseline
  • Participants who received AMX0035 at baseline lived significantly longer than predicted by the model (25.0 vs. 13.5 months from randomization, respectively)
  • Participants who received placebo at baseline (including participants who crossed over to the OLE and received AMX0035) showed longer survival than predicted in the model (18.4 vs. 12.0 months respectively)
  • Participants who received placebo at baseline and did not cross over to the OLE did not show significant differences compared to the predictions of the model

“We are thrilled to share the results from CENTAUR at the International Symposium on ALS/MND,” said Patrick Yeramian, M.D., Chief Medical Officer at Amylyx. “The statistically significant results for the prespecified overall survival and functional analyses provide strong evidence for the benefit of AMX0035 in ALS. The exploratory natural history analysis using the ENCALS survival prediction model adds further confirmation. We are working hard to move this investigational product forward quickly in light of these promising results and will continue to update the ALS community on our progress.”

The development and validation of the ENCALS survival prediction model using data from >10,000 European patients with ALS was described by Westeneng et al in 2018. The model is expected to perform similarly in a U.S. population and has been cross-validated across non-U.S. datasets. However, it has not yet been validated in a U.S. population and is considered exploratory.

Presentation Details:

Title: Functional and long-term survival benefit of AMX0035 in ALS: results of the CENTAUR and Open Label Extension trials
Abstract #: C7
Date: Wednesday, December 9, 2020
Time: 11:30 a.m. ET

About CENTAUR

CENTAUR was a 24-week, randomized, double-blind, placebo-controlled Phase 2/3 clinical trial that evaluated the safety and tolerability of AMX0035 and assessed the drug’s impact on disease progression as measured by the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) when compared to placebo. The trial also assessed the effects of AMX0035 on other measures that are critical to people with ALS, including muscle strength, lung vital capacity, and biomarkers of neuronal degeneration.

CENTAUR was the recipient of the ALS ACT grant, and is supported by The ALS Association, ALS Finding a Cure, a program of The Leandro P. Rizzuto Foundation, the Northeast ALS Consortium, Healey Center for ALS at Mass General, and was funded in part by the ALS Ice Bucket Challenge.

CENTAUR enrolled patients 18-80 years old with definite ALS and within 18 months of symptom onset. The trial did not restrict patients from receiving edaravone or riluzole. Participants who completed CENTAUR were given the option after the trial to enroll in an open-label extension study and receive AMX0035 for up to 30 months (132 weeks). 92% of eligible CENTAUR participants elected to enroll in the extension study. More information on the CENTAUR trial can be found at https://www.amylyx.com/science/ or www.clinicaltrials.gov, NCT03127514 or NCT03488524.

About Amyotrophic Lateral Sclerosis (ALS)

ALS is a relentlessly progressive and fatal neurodegenerative disorder caused by motor neuron death in the brain and spinal cord. Motor neuron loss in ALS leads to deteriorating muscle function, the inability to move and speak, respiratory paralysis, and eventually death. The vast majority of patients with ALS (>90%) have sporadic disease, showing no clear family history. Approximately 6000 people are diagnosed with ALS in the United States every year with an approximately similar number of deaths every year.

About AMX0035

AMX0035 is an investigational product designed to reduce neuronal death and dysfunction. AMX0035 targets endoplasmic reticulum and mitochondrial dependent neuronal degeneration pathways in ALS and other neurodegenerative diseases.

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.

Merissa Muller
Finn Partners
(617) 778-6633
Merissa.Muller@finnpartners.com

Source: Amylyx Pharmaceuticals, Inc.