CAMBRIDGE, Mass.– Amylyx Pharmaceuticals, Inc. (Nasdaq: AMLX) (“Amylyx” or the “Company”) today announced the publication of analyses performed on neuroinflammatory biomarkers using plasma samples from participants with amyotrophic lateral sclerosis (ALS) from the Phase 2 CENTAUR trial. These findings were published in the peer-reviewed medical journal, Journal of Neurology, Neurosurgery and Psychiatry. During the CENTAUR trial, plasma samples were prospectively collected from trial participants for future biomarker analyses. Post hoc analyses were conducted to look at the impact of AMX0035 on biomarkers shown to correlate with ALS disease progression, including chitinase biomarkers such as YKL-40 (also known as chitinase-3-like protein 1), chitinase 1 (CHIT1), and the systemic inflammatory biomarker C-reactive protein (CRP). The results of these post hoc analyses demonstrated a significant reduction in plasma concentrations of YKL-40 and CRP, but not CHIT1, over 24 weeks, with reductions observed as early as Week 12 in participants from the CENTAUR trial.
“Neuroinflammatory biomarkers are important for assessing disease progression and therapeutic response in ALS with chitinases and CRP emerging as potential treatment response biomarkers. Previous studies have shown that levels of YKL-40 in cerebrospinal fluid correlate with ALS disease progression rate, severity, and survival,” said Robert Bowser, PhD, Chief Scientific Officer of Barrow Neurological Institute. “The learnings from these analyses are an important step linking the biological impact of AMX0035 with potential key biomarkers for ALS.”
“Biomarkers linking clinical therapeutic effect with biological changes are of high interest in ALS, and the findings from these analyses suggest that YKL-40 could be a treatment-sensitive biomarker,” said Machelle Manuel, PhD, Head of Global Medical Affairs at Amylyx. “YKL-40 and CRP concentration decreased significantly for the group of participants that received AMX0035 compared to placebo and were correlated with disease progression as measured by the ALSFRS-R, further demonstrating the impact of AMX0035.”
Of the 135 participants in the modified intent-to-treat population (ITT) of the CENTAUR trial, 126 had plasma samples available for these analyses. The analyses showed that geometric least squares (LS) mean YKL-40 and CRP plasma concentrations were 10% and 17% lower, respectively, at Week 12 and approximately 20% and 30% lower, respectively, at Week 24 in the AMX0035 versus placebo group. YKL-40 and CRP concentrations correlated with ALSFRS-R total score and ALSFRS-R slope. Geometric LS mean CHIT1 plasma levels were not significantly different between treatment groups. Further analyses of neuroinflammatory biomarkers are planned in the ongoing Phase 3 PHOENIX trial to confirm these results.
