BIAL, a biopharmaceutical company focused on neurosciences and rare diseases, announced a key milestone in its Phase 2 clinical trial (ACTIVATE) of BIA 28-6156, with the first patient completing the full dose regimen. This study is evaluating the drug as a novel therapy for Parkinson's disease (PD) patients who have a mutation in the glucocerebrosidase 1 (GBA1) gene (GBA-PD). The ACTIVATE study (NCT05819359) is a Phase 2, multicenter, randomised, double-blind, placebo-controlled study evaluating the efficacy, safety, tolerability, pharmacodynamics, and pharmacokinetics of two fixed-dose levels (10mg/day and 60mg/day) of BIA 28-6156. Topline data from this Phase 2 study is expected to be released in mid-2026.
Novel Approach to GBA-PD Treatment
BIA 28-6156 represents a first-in-class therapeutic approach as a small molecule allosteric activator of beta-glucocerebrosidase (GCase). Administered orally once daily, it aims to increase GCase activity and re-establish sphingolipid recycling, potentially modifying the underlying cause of GBA-PD. Preclinical data suggest that BIA 28-6156 can cross the blood-brain barrier and has a low toxicity profile.
Clinical Significance and Expert Commentary
Joerg Holenz, BIAL's Chief Scientific Officer, stated, "The first patient out in the ACTIVATE study marks a pivotal milestone in the development of BIA 28-6156, as well as for our ambition to create transformative value for people living with neurodegenerative diseases. We are confident that our medicine has the potential to become a groundbreaking, novel treatment for patients with a confirmed diagnosis of GBA-PD. BIA 28-6156 offers a specific, potentially disease-modifying mechanism of action, with the potential to delay clinical motor progression."
Professor Joaquim Ferreira, an ACTIVATE study investigator, highlighted the significance of this milestone, noting the successful recruitment of over 230 genetically confirmed GBA-PD patients across 85 sites in Europe and North America. He expressed immense anticipation for the potential of BIA 28-6156, not only for the GBA-PD patient community but also for the broader Parkinson's community."
Parkinson's Disease and GBA1 Mutations
Parkinson's disease is the second most common neurodegenerative disorder, affecting more than 10 million people globally. Between 5% and 15% of PD patients have mutations in the GBA gene, making it the most important genetic risk factor for PD. GBA-PD patients often experience an earlier onset of symptoms, more severe clinical manifestations, and a faster rate of disease progression compared to those with idiopathic PD.
ACTIVATE Study Design
The ACTIVATE study is designed to evaluate the efficacy, safety, tolerability, pharmacodynamics, and pharmacokinetics of two fixed-dose levels (10mg/day and 60mg/day) of BIA 28-6156. The primary endpoint is to assess the delay of meaningful clinical progression as assessed by the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II and Part III up to 78 weeks of double-blind treatment period.
