Amylyx Pharmaceuticals Highlights New Long-Term Safety Data from CENTAUR Study of AMX0035 in People with ALS at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2020 Virtual Meeting
- Data from New Long-Term Safety Analysis Show No New Safety Concerns with AMX0035 Identified in the Open-Label Extension Study
- Data Were Consistent with Primary Outcome of Statistically Significant Slowing of the Functional Decline Associated with the Administration of AMX0035
- Company Also Presented Secondary Outcome Results Demonstrating the Administration of AMX0035 Resulted in Statistically Significant Slower Rate of Decline in Arm Muscle Strength, but Not Leg Muscle Strength
CAMBRIDGE, Mass. Oct. 9, 2020–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 new long-term safety data, as well as muscle strength results, from the CENTAUR study evaluating AMX0035 in people with ALS at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2020 Virtual Meeting held October 7-10, 2020.
CENTAUR was a 24-week placebo-controlled study of 137 participants with ALS that evaluated the safety and efficacy of AMX0035. As previously reported, the study met its primary efficacy endpoint of slowing ALS as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R).
“Patients with ALS are often taking multiple medications to manage their disease, so it is especially important to demonstrate whether AMX0035 is safe and tolerable for them long-term,” said Dr. Sabrina Paganoni, M.D., Ph.D., principal investigator of the CENTAUR study, 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. “The majority of patients in CENTAUR were receiving one or more FDA approved ALS therapies before or at the start of the study. We were able to show that AMX0035 was generally well tolerated whether taken alone or on top of FDA approved therapies for up to 35 months. These results support the potential value of AMX0035 as a long-term treatment for ALS.”
Long-Term Safety Results from CENTAUR OLE:
Participants in CENTAUR were given the option after the trial to enroll in an open-label extension (OLE) study to receive AMX0035 long-term (up to 35 months). 92% of participants who completed CENTAUR elected to enroll in the extension study. In the randomized controlled portion of CENTAUR, participants experienced similar rates of adverse events recorded in the AMX0035 and placebo groups. No new safety concerns were noted in the open-label extension.
- Gastrointestinal (GI) adverse events (AEs) in the AMX0035 group were reported most frequently in the first 3 weeks. Participants switching to AMX0035 from placebo in the OLE reported similar events and timing.
- 27% (9/34) of participants switching to AMX0035 from placebo in the OLE reported diarrhea vs. 9% (5/56) of participants continuing AMX0035 in the OLE.
- Most adverse events did not lead to study drug modification, interruption, or withdrawal.
- GI AEs and respiratory failure were the most commons AEs leading to study drug discontinuation.
- Additional analyses of safety and functional data from the OLE are underway.
“We are excited to have longer-term safety data on AMX0035,” said Josh Cohen, Co-CEO, Chairman and Co-Founder at Amylyx. “The data on AMX0035 suggests that it has a manageable safety profile and these data support the continued development of this investigational drug. We are pressing ahead rapidly and will continue to update the community.”
Accurate Test of Limb Isometric Strength (ATLIS) Results from CENTAUR:
CENTAUR is the first trial to utilize ATLIS (Acute Test of Limb Isometric Strength), a new test developed to precisely and conveniently measure muscle strength in order to reduce variability and increase sensitivity in clinical trials of ALS. It measures the maximum voluntary isometric contraction (MVIC) of six arm and six leg muscle groups. ATLIS was a secondary outcome measure of disease progression in CENTAUR. In this study, mean rate of change per month in ATLIS scores trended toward AMX0035 benefit, with the arm score reaching significance (P=0.04). The leg muscle strength score did not reach statistical significance.
“We want to thank all CENTAUR participants who have made our progress with AMX0035 possible,” said Justin Klee, Co-CEO and Co-Founder of Amylyx. “We understand that people living with ALS do not have time to wait and are working tirelessly to further develop this potential treatment option. Data from a long-term survival analysis of all CENTAUR participants have been submitted to a peer-reviewed journal. Additional safety and efficacy analyses from the CENTAUR OLE study are ongoing and will be presented in the near future.”
Title: Accurate Testing of Limb Isometric Strength (ATLIS™) For Measuring Muscle Strength In Amyotrophic Lateral Sclerosis: Results From the CENTAUR Trial
Poster #: 194
Date: Oct. 9, 2020
Time: 4:15-4:45 p.m. EST
Title: Long-Term Treatment with AMX0035 in the Open-Label Extension of CENTAUR, a Randomized Controlled Trial in Individuals with Amyotrophic Lateral Sclerosis
Poster #: 195
Date: Oct. 10, 2020
Time: 4:15-4:45 p.m. EST
Posters presented at the AANEM Virtual Meeting will be available for viewing to meeting attendees for 30 days on the AANEM website.
CENTAUR was a 24-week, randomized, double-blind, placebo-controlled 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, Sean M. Healey & AMG 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://amylyx.com/trials/ 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.
AMX0035 is an investigational neuroprotective therapy 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.