Bial drops Parkinson’s therapy after it fails to slow disease in trial
BIA 28-6156 didn't meet goals in Phase 2 trial involving gene mutation
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- Bial discontinued BIA 28-6156 for GBA-related Parkinson's after it failed to slow disease progression in a Phase 2 trial.
- GBA-related Parkinson's, caused by GBA1 gene mutations, often leads to earlier, more severe symptoms and faster disease progression.
- The failed trial provides insights for understanding Parkinson's and development of new therapies.
BIA 28-6156, a small-molecule therapy developed by Bial for GBA-related Parkinson’s disease, did not slow disease progression in a Phase 2 clinical trial involving people with mutations in the GBA1 gene, and the company decided to discontinue its development for the condition.
Bial said that while the study data provided valuable scientific insights into Parkinson’s mechanisms, BIA 28-6156 did not perform significantly better than a placebo based on either the primary or key secondary endpoints of the ACTIVATE trial (NCT05819359).
“While we would have hoped for better news for the broader Parkinson’s community, the ACTIVATE study provides many valuable insights and learnings for the field, being crucial for enhancing our understanding of Parkinson’s,” Joerg Holenz, PhD, Bial’s chief scientific officer, said in a company press release. “We will use these findings to inform the community and to accelerate our efforts to develop new therapeutic solutions in this indication.”
Mutations in the GBA1 gene, which provides instructions for producing the GCase enzyme, are one of the most common genetic causes of Parkinson’s. When the enzyme is faulty or missing, toxic clumps of misfolded proteins, such as alpha-synuclein, accumulate in nerve cells, contributing to Parkinson’s symptoms.
In people with GBA-related Parkinson’s, symptoms frequently develop earlier and are more severe, and the disease usually progresses faster than in patients without these mutations.
Treatment aimed to address underlying cause
BIA 28-6156, previously LTI-291, is an oral small molecule designed to bind to GCase and increase its activity. This was intended to prevent the accumulation of misfolded proteins and nerve cell damage, meaning the treatment was expected to modify the disease’s underlying cause in GBA-related Parkinson’s.
The safety, tolerability, and efficacy of BIA 28-6156 were investigated in several Phase 1 clinical trials conducted by Lysosomal Therapeutics, the company that initially developed the molecule. Two trials in healthy volunteers demonstrated that BIA 28-6156 levels reaching the brain were sufficient to double GCase activity.
A Phase 1b study that enrolled people with GBA-Parkinson’s found biomarker evidence of increased GCase activity at several treatment doses. Another study showed that the treatment improved patients’ brain blood flow, nerve cell activity, and functional connectivity.
The ACTIVATE study evaluated the treatment’s safety, tolerability, efficacy, and pharmacological properties in 273 adults with GBA-Parkinson’s across 85 clinical sites in 11 countries in Europe and North America. Participants were randomly assigned to receive 10 mg or 60 mg of BIA 28-6156, or a placebo, once daily for approximately 18 months.
The trial’s main goal was to assess the time to clinically meaningful progression in motor aspects of experiences of daily living as assessed by MDS-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) parts 2 and 3.
Secondary goals included changes in the progression of motor symptoms, other measures of disease severity, and patient-reported changes in Parkinson’s symptoms and health-related quality of life.
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