Amylyx Pharmaceuticals Announces Publication of New CENTAUR Trial Analyses Further Demonstrating Significant Survival Benefit with AMX0035 in People with ALS

• An analysis using the rank-preserving structural failure time model (RPSFTM), a method frequently employed in oncology to account for placebo crossover, estimated a 10.6-month longer median survival duration for AMX0035 participants
• Participants randomized to receive AMX0035 and who continued into the open-label extension (OLE) phase showed an 18.8-month longer median survival duration than participants who never received AMX0035 in a subgroup analysis

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Amylyx Pharmaceuticals, Inc. (Nasdaq: AMLX) (“Amylyx” or the “Company”) today announced the publication of long-term survival analyses of the Phase 2 CENTAUR trial adjusting for treatment crossover of the placebo group. The post hoc analyses suggested a larger survival benefit for AMX0035 (sodium phenylbutyrate [PB] and taurursodiol [TURSO; also known as ursodoxicoltaurine]) when adjusting for placebo crossover ranging from 10.6 to 18.8 months compared with 6.9 months seen in the original prespecified intent-to-treat (ITT) analysis in participants with amyotrophic lateral sclerosis (ALS). These results are published in the peer-reviewed medical journal, Muscle & Nerve.

“Trials that incorporate placebo-to-active treatment crossover are critically important in rapidly fatal diseases like ALS, however, this design may underestimate the clinical effect of investigational therapies,” said Machelle Manuel, Ph.D., Head of Global Medical Affairs of Amylyx. “Fortunately, statistical models, like the RPSFTM, allow us to adjust results for treatment crossover. Here, similar to the prespecified ITT analysis, we observed a significant survival benefit for AMX0035 in the survival analyses adjusting for treatment crossover, potentially offering those living with ALS and their families hope of sharing more memories and milestones together.”

Survival analyses incorporated updated participant vital status information from the prior interim ITT analysis. The final dataset compared time to death (all-cause mortality) from the point of randomization in the Phase 2 CENTAUR trial through a cutoff date of July 20, 2020 (longest follow-up, 35 months after randomization) and the date of the final open-label extension (OLE) phase participant visit (March 1, 2021, up to 42 months after randomization). Vital status could be determined for all but one participant who was censored at the date of last follow-up. Post hoc analyses performed included a RPSFTM and subgroup analysis.

• As of the July 2020 cutoff date, results of the final overall survival ITT analysis showed a significantly longer median survival duration of 6.9 months in those originally randomized to AMX0035 compared to those originally randomized to placebo (hazard ratio [HR], 0.57; 95% CI, 0.35–0.92; P=.023).
  • At the March 2021 cutoff date, results showed a significantly lower hazard of death and longer median survival duration of 4.8 months in those originally randomized to AMX0035 compared to those originally randomized to placebo (HR 0.64; 95% CI, 0.42-1.00; P=.048).
• Results of the statistical methods that account for treatment crossover (RPSFTM and subgroup analyses) showed a greater survival benefit compared to ITT analysis.
  • As of the July 2020 cutoff date, the observed median survival of 25.8 months in those originally randomized to AMX0035 compared to RPSFTM-adjusted median survival of 15.2 months in those originally randomized to placebo, a 10.6-month difference, with an HR of 0.39 (95% CI, 0.17–0.88; P=.023).
  • The RPSFTM analysis models what the survival outcome from the placebo group would have been had participants not switched to AMX0035 in the OLE phase.
  • At the March 2021 cutoff date, the same RPSFTM analyses were performed and yielded consistent results.
• As of the July 2020 cutoff date, post hoc assessment of subgroups based on randomization group as well as enrollment in the OLE phase demonstrated that participants who were originally randomized to AMX0035 and then enrolled in the OLE phase survived 18.8 months (P