RARE Daily

NEJM Publishes Pivotal Amylyx Data Demonstrating Benefit of AMX0035 in ALS

September 3, 2020

Rare Daily Staff

Amylyx Pharmaceuticals reported the publication of positive results from the pivotal CENTAUR trial evaluating its experimental neuroprotective therapy AMX0035 in people with ALS in The New England Journal of Medicine.

ALS, also known as Lou Gehrig’s disease, is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. The progressive neurodegeneration in ALS eventually leads to the death of motor neurons and loss of the ability of the brain to initiate and control muscle movement. With muscle action progressively affected, patients in the later stages of the disease may become paralyzed and unable to breathe normally.

The CENTAUR trial of 137 individuals with ALS was conducted across 25 top medical centers in the U.S. through the Northeast ALS (NEALS) consortium. It demonstrated that treatment with AMX0035 was well tolerated and decreased the rate of decline in the Revised ALS Functional Rating Scale (ALSFRS-R) compared to placebo in people with ALS, the primary study outcome.

After 24 weeks, patients treated with AMX0035 scored on average 2.32 points higher on the ALSFRS-R than the placebo group using the study’s primary pre-specified analysis. A change from baseline analysis was also conducted and indicated that 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 measuring daily functions, such as the ability to walk, dress independently, self-feed, speak and breathe. Just a 1 to 2 point change in the ALSFRS-R score can indicate a significant reduction in a patient’s ability to function independently. Some examples of a two point change on this scale include the difference between an individual eating successfully with some difficulty versus needing a feeding tube, or walking with assistance versus not walking at all.

AMX0035 also showed benefits on secondary outcomes including measures of muscle strength, breathing, and hospitalizations. It was generally well tolerated with similar rates of adverse events recorded in the dosed and placebo groups.

“The data published today in the New England Journal of Medicine show that AMX0035 demonstrated a clinically meaningful benefit and a favorable safety profile for people living with ALS,” said Josh Cohen, co-CEO, chairman and co-founder at Amylyx.

“This development is a breakthrough for the ALS community, and we are working collaboratively and expeditiously with agencies worldwide to bring this potential new treatment option forward.”

Three quarters of CENTAUR participants were receiving an approved ALS therapy (riluzole, edaravone, or both) during and/or before trial entry. Sensitivity analyses accounting for the duration of treatment under riluzole, edaravone, or both confirmed that the treatment effect of AMX0035 was independent of background approved ALS therapies.

“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 CEO of The ALS Association.

More than 90 percent of participants who completed CENTAUR elected to enroll in an open-label extension study and receive AMX0035 long-term. Interim data from the ongoing open-label extension study are being submitted to a peer-reviewed journal shortly and will be published in the coming months.

Long-term survival analysis for the patients in the AMX0035 and placebo groups has been conducted as well. These data will be submitted to a peer-reviewed journal in the near future.

The CENTAUR trail 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.

Photo: Josh Cohen, Co-CEO, chairman and co-founder at Amylyx


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