BIAL R&D has commenced its Phase 2 clinical trial, named ACTIVATE, by dosing the first patient to evaluate BIA 28-6156 for treating Parkinson's disease (PD) in patients with a mutation in the glucocerebrosidase 1 (GBA1) gene (GBA-PD). Parkinson's disease, the second most common neurodegenerative disorder, has GBA1 gene mutations identified as the most common genetic risk factor.
The ACTIVATE study is a Phase 2, multicenter, randomized, double-blind, placebo-controlled study designed to assess the efficacy, safety, tolerability, pharmacodynamics, and pharmacokinetics of two fixed dose levels of BIA 28-6156 (10mg and 60mg/day). Approximately 237 genetically confirmed GBA-PD subjects will be randomized into three treatment arms: 10mg BIA 28-6156, 60mg BIA 28-6156, or placebo. The primary endpoint is the time to meaningful clinical progression, evaluated by the Movement Disorder Society - Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Parts II and III, over a 78-week double-blind treatment period.
BIA 28-6156: A Novel Approach to Parkinson's Treatment
BIA 28-6156, previously known as LTI-291 or LTI-00291, is a novel allosteric activator of beta-glucocerebrosidase (GCase). It is under development by BIAL R&D for treating Parkinson's disease (PD) in patients with a mutation in the glucocerebrosidase 1 (GBA1) gene (GBA-PD). The drug is a small molecule designed for oral administration, once daily, with a low toxicity profile and the ability to cross the blood-brain barrier, as validated in vitro and in vivo studies.
Study Design and Patient Enrollment
The ACTIVATE study is enrolling subjects with PD diagnosed between 1 to 7 years before genetic screening, a modified Hoehn and Yahr score ≤2.5, and a score of ≥22 on the Montreal Cognitive Assessment. Participants must be receiving a stable dose of PD medication, which will continue throughout the study. Patient screening is underway across sites in North America, with plans to expand to the EU in Q3 2023. Additional details about the trial design can be found at www.clinicaltrials.gov (identifier: NCT05819359).
Mechanism of Action and Potential Benefits
According to Nuno Mendonça, Chief Medical Officer of BIAL, "Activation of GCase enzymatic activity via allosteric modulation with BIA 28-6156 offers a novel potential treatment for patients with GBA-PD as well as a promising new approach to delay clinical motor progression. Data from nonclinical settings, including data from human cells, suggest that activation of GCase enzymatic activity could provide therapeutic benefit to patients with PD who carry a GBA-PD risk-associated variant in the GBA1 gene."
About BIAL R&D
BIAL - R&D Investments S.A. (BIAL R&D), a subsidiary of BIAL Holding, S.A., is dedicated to discovering new drugs for human use. BIAL R&D owns intellectual property related to pharmaceutical compounds for neurodegenerative diseases, including BIA 28-6156. BIAL consistently invests over 20% of its annual turnover in R&D, with a major focus on neurosciences.
