October 5, 2026

@michaelokun

The Phase 2b ACTIVATE trial tested whether BIA 28-6156, an oral activator of the GCase enzyme, could slow progression in Parkinson’s disease associated with GBA1 variants. Data just dropped in Seoul at the MDS meeting. In this 78-week, double-blind, placebo-controlled study, 272 participants received BIA 28-6156 at 10 mg/day, 60 mg/day, or placebo. Despite a compelling biological rationale, neither dose slowed clinical progression on the primary MDS-UPDRS outcome or the key motor secondary outcome, and exploratory analyses showed no dose-response or efficacy signal. The encouraging news was that BIA 28-6156 was well tolerated, with adverse events and discontinuation rates similar to placebo. Overall, this was a negative efficacy trial, but an important one that raises critical questions about whether activating GCase remains the right disease-modifying strategy, whether treatment needs to begin earlier, and whether different biomarkers or clinical endpoints will be needed to adequately test this approach. https://www.mdscongress.org/Abstracts/Late-breaking