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Cambridge, Massachusetts-based Amylyx Pharmaceuticals published data from its Phase II/III CENTAUR clinical trial evaluating AMX0035 in amyotrophic lateral sclerosis (ALS). The research was published in the New England Journal of Medicine.
The trial met its primary endpoint, showing a clinically meaningful and statistically significant treatment benefit based on the Revised ALS Functional Rating Scale (ALSFRS-R). The trial evaluated 137 people with ALS and was conducted at 25 medical centers in the U.S. through the Northeast ALS (NEALS) consortium.
ALS is a progressive and fatal neurodegenerative disorder. It is caused by motor neuron death in the brain and spinal cord. It leads to loss of muscle function, the inability to move and speak, respiratory paralysis, and eventually death. It affects about 6,000 people in the U.S. with about the same number of deaths each year. It is also known as Lou Gehrig’s disease.
AMX0035 is a neuroprotective therapy designed to decrease neuronal death and dysfunction. It targets endoplasmic reticulum and mitochondrial dependent neuronal degeneration pathways in ALS.
“The data published today makes a clear and compelling case that AMX0035 should be made available to people with ALS as soon as possible,” said Calaneet Balas, president and chief executive officer of The ALS Association. “We look forward to working with Amylyx, the FDA, and the entire community to help make that happen. We are grateful to all the Ice Bucket Challenge donors whose contributions helped make this trial possible.”
In the CENTAUR trial, after 24 weeks, patient receiving AMX035 scored an average 2.32 points higher on the ALSFRS-R than the placebo group. On an analysis of change from baseline, the AMX0035 group scored 2.92 points higher at the end of the 24-week follow-up. The ALSFRS-R is a 48-point questionnaire that includes measures of daily function such as ability to walk, dress independently, self-feed, speak and breathe. A one to two-point change in the ALSFRS-R can mean a significant decrease in a person’s ability to function independently.
Secondary endpoints included measurements of muscle strength, breathing and frequency of hospitalization. Patients taking AMX0035 had a slower progression in lung function and were hospitalized numerically less often. The trial was not powered to include secondary endpoints, but the data was promising.
The drug was generally well tolerated, although almost all participants, 86 out of 89 receiving the drug, reported one or more treatment-emergent adverse events. Most were not serious and did not lead to modification or interruption of the drug dosing. Otherwise, safety between the placebo and AMX0035 groups was comparable. Almost all participants, 77%, were receiving an approved ALS therapy, riluzole, edaravone, or both, during or before the trial.
One potential downside of the study is that it only lasted six months, so it did not determine if the drug prolonged survival of the ALS patients. However, the trial is continuing, and the company plans to publish long-term survival data later. Patients who completed CENTAUR were offered the chance to enroll in an open-label extension trial and receive AMX0035 long-term, with 92% choosing to do so.
“We are deeply grateful to all of the CENTAUR participants and our partners who have helped and continue to help develop this important therapy for those living with ALS,” said Justin Klee, co-chief executive officer and co-founder of Amylyx. “We also look forward in the coming months to sharing results from the CENTAUR open-label extension study and the long-term survival analysis, and we will continue to keep the community closely informed on next steps.”