RARE Daily

Amylyx Publishes Results of ALS Study Showing Statistically Significant Survival Benefit

October 19, 2020

Rare Daily Staff

Amylyx Pharmaceuticals said it has published a study showing that it’s experimental therapy AMX0035 demonstrated a statistically significant survival benefit in patients with the rare neurodegenerative condition ALS.

The study, published in the journal Muscle & Nerve is based on an analysis of participants in the CENTAUR trial who were followed for up to three years from the start of the study, whether or not they continued long-term treatment in the open-label extension portion of the trial. It found that participants treated with AMX0035 had a 44 percent lower risk of death compared to participants who originally received placebo over the duration of follow-up.

ALS is a 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. More than 90 percent of patients with ALS have sporadic disease, showing no clear family history. Approximately 6,000 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. These pathways represent a different approach from currently approved drugs riluzole and edaravone.

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.

Most CENTAUR participants (77 percent) were receiving an approved ALS therapy (riluzole, edaravone, or both) during and/or before trial entry and could continue these medications during the open-label extension. The company said sensitivity analyses accounting for concomitant approved ALS therapies confirmed the published function and survival benefits of AMX0035 were independent of background medication use.

As previously reported, the CENTAUR study also met its primary efficacy endpoint of slowing ALS as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R) versus placebo over a six-month period. AMX0035 was generally well tolerated with a manageable safety profile. The company said the publications highlight that administration of AMX0035 resulted in both functional and survival benefits in people with ALS.

“We have many reasons to be encouraged today,” said Sabrina Paganoni, principal investigator of the CENTAUR trial, investigator at the Sean M. Healey & AMG Center for ALS at Mass General. “In this trial, we have seen promising functional and survival benefits.”

Participants in CENTAUR were given the option after the trial to enroll in an OLE study to receive AMX0035. 92 percent of participants who completed CENTAUR elected to enroll in the extension study. Long-term functional and safety data from the CENTAUR and OLE studies are also being submitted to a peer reviewed journal and planned for publication soon. Interim data from the ongoing extension study will be presented in 2020.

Photo: Sabrina Paganoni, principal investigator of the CENTAUR trial, investigator at the Sean M. Healey & AMG Center for ALS at Mass General

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