AL-S Pharma has presented phase 2 clinical study results on AP-101 to treat amyotrophic lateral sclerosis (ALS) at the 36th International Symposium on ALS/MND in San Diego.
AP-101 is an investigational human antibody therapeutic selectively targeting misfolded SOD1 to disrupt the progressive spread of pathology in ALS. The global phase 2 study with 73 participants met its primary endpoint related to safety and tolerability. Adverse events were comparable to placebo, and no AP-101-induced antibody responses were reported.
The analysis of an exploratory composite endpoint revealed that early treatment with AP-101 prolonged survival and delayed ventilatory support in comparison to study participants receiving placebo for 6 months followed by 6 months of treatment with AP-101. Positive treatment effects were observed in both the sporadic ALS cohort and the SOD1 mutation carrier cohort. Effects on survival were accompanied by disease stabilisation as measured by King’s staging. Functional decline measured by ALSFRS-R was reduced in study participants with elevated misfolded SOD1 at baseline and in SOD1 mutation carriers. In addition, AP-101 treatment resulted in favourable neurofilament biomarker changes aligned with clinical benefit.
“We are very excited by the positive phase 2 results for AP-101,” said Angela Genge, chief medical officer of AL-S Pharma.
“We are observing very consistent results across survival, function, and biomarkers in two independent cohorts within our study. Despite the statistical limitations of a phase 2 study, the exploratory outcome data indicates that treatment with AP-101 results in a clinically meaningful treatment effect in both sporadic ALS as well as SOD1-ALS patients.”
The 2 study results with AP-101 are consistent with the hypothesis that targeting misfolded SOD1 is a disease-modifying approach in ALS.2 AL-S Pharma is currently preparing for a confirmatory phase 3 clinical study.
The AP-101-02 study was a global, randomised, double-blind, placebo-controlled study evaluating safety, tolerability, pharmacodynamic markers, and pharmacokinetics of AP-101 in study participants with sporadic ALS and mutant SOD1-ALS over 6 months followed by a 6-months open-label extension and a safety follow-up period.
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