Amylyx Pharmaceuticals announces New England Journal of Medicine publication of pivotal AMX 0035 data demonstrating statistically significant benefit in people with ALS.

Amylyx Pharmaceuticals, Inc., a pharmaceutical company focused on developing new treatments for amyotrophic lateral sclerosis (ALS), Alzheimer’s disease and other neurodegenerative diseases, announced the publication of results from the pivotal CENTAUR trial evaluating AMX 0035 – an investigational neuroprotective therapy designed to reduce the death and dysfunction of motor neurons – in people with ALS in the New England Journal of Medicine (NEJM). .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 AMX 0035 was well tolerated and decreased the rate of decline in the ALSFRS-R compared to placebo in people with ALS. CENTAUR Results : Primary Outcomes : After 24 weeks, patients treated with AMX 0035 scored on average 2.32 points higher on the ALSFRS-R than the placebo group (p=0.03) using the study’s primary prespecified analysis. A change from baseline analysis was also conducted and indicated that the AMX 0035 group scored 2.92 points higher at the end of 24 week follow up (p=0.01). 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 1-2 point change in the ALSFRS-R score can indicate a significant reduction in a patient’s ability to function independently. The ALSFRS-R measures many different daily functions so point differences can manifest differently in different patients. Some examples of a two point change on this scale include the difference between an individual eating successfully with some difficulty vs needing a feeding tube, or walking with assistance versus not walking at all. Secondary Outcomes :In line with the primary outcome, patients on AMX 0035 also showed numerical benefits on secondary outcomes including measures of muscle strength, breathing and hospitalization frequency, although the study was not powered for secondary outcomes. Progression in lung function (percent predicted slow vital capacity) was numerically slower in patients taking AMX 0035 (Least Squares Difference=5.11 points, p=0.08). Participants in the AMX 0035 group were hospitalized numerically less often (Hazard Ratio = 0.54, p=0.09). Rate of decline in overall muscle strength (percent predicted ATLIS) was numerically slower in patients taking AMX 0035 (Least Squares Difference=2.82 points, p=0.12). The effect of AMX 0035 on progression was nominally statistically significant for the upper limbs measurements (Least Squares Difference=4.27 points, p=0.04). Overall Safety : Nearly all participants (46 out of 48 patients in placebo (96%) vs 86 out of 89 patients in the AMX 0035 group (97%)) reported one or more treatment-emergent adverse events (TEAEs) during the trial. Most were non-serious, did not lead to modification or interruption of study drug dosing, and were not considered related to the study. Overall, safety was comparable between the groups, with fewer serious adverse events in the active group as compared to the placebo group (9 out of 48 patients (19%) in placebo vs 11 out of 89 patients (12%) in the AMX 0035 group). GI adverse events, which were generally characterized as mild by investigators, occurred more frequently in the active group in the first 3 weeks of the trial (28.1% vs 12.5% placebo) and returned to levels comparable to placebo thereafter. Most CENTAUR participants (77%) 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 AMX 0035 was independent of background approved ALS therapies. AMX 0035 Long-Term Survival and Extension Data, Future Plans : Participants who completed CENTAUR were given the option after the trial to enroll in an open-label extension study and receive AMX 0035 long-term. 92% of eligible CENTAUR participants elected to enroll in the extension study. 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 AMX 0035 and placebo groups has been conducted as well. These data will be submitted to a peer-reviewed journal in the near future.