Study of Bial therapy for patients with GBA1 mutations advances
First Parkinson's patient completes dosing in Phase 2 study of BIA 28-6156
The first patient in a Phase 2 clinical study testing BIA 28-6156 — a small molecule in the pipeline at Bial for treating Parkinson’s disease in people with mutations in the GBA1 gene — has completed the full dose regimen, the company announced.
The goal of the study, called ACTIVATE (NCT05819359), is to check how well BIA 28-6156 works against a placebo in delaying the clinical progression of motor symptoms in people with GBA1 mutations — who are said to have GBA-PD. These patients often develop symptoms more quickly than those without mutations in this gene.
ACTIVATE, which has enrolled more than 200 patients, will span 78 weeks, or about 1.5 years. Top-line data are expected by mid-2026.
The study also will test the safety of BIA 28-6156 when taken by mouth at a daily dose of either 10 or 60 mg. Also under investigation will be the therapy’s pharmacokinetics, meaning how it moves into, through, and out of the body, and its pharmacodynamics, or its effects on the body.
“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,” Joerg Holenz, PhD, Bial’s chief scientific officer, said in a company press release.
ACTIVATE testing BIA 28-6156 in over 200 patients with GBA1 mutations
The ACTIVATE study is being conducted at 95 locations in the U.S., Canada, and several countries in Europe.
According to Joaquim Ferreira, MD, PhD, an ACTIVATE investigator and member of the study’s steering committee, “there is immense anticipation surrounding the potential of BIA 28-6156, not only for the GBA-PD patient community but also for the broader Parkinson’s community.”
The completion of dosing in the first study participant is a key milestone, according to Bial.
“This step follows the remarkable success of the recruitment phase, which has enrolled over 230 genetically confirmed GBA-PD patients across 85 sites in Europe and North America,” said Ferreira, also a professor at the Lisbon School of Medicine in Portugal. The study is now active and no longer recruiting.
Mutations in GBA1, the gene that provides instructions for producing an enzyme called GCase, are a major risk factor for developing Parkinson’s. When GCase is faulty or missing, toxic clumps of misfolded proteins build up around nerve cells in the brain, causing the disease’s symptoms.
Patients with this form of Parkinson’s, known as GBA-PD, often develop symptoms earlier than those with idiopathic Parkinson’s — when the disease has no known cause. Symptoms in those with GBA-PD also are more severe and usually progress faster than in patients without these gene mutations. As such, according to the researchers, there is a need for treatments that can delay how fast motor symptoms progress.
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.
BIA 28-6156 is designed as an allosteric activator of GCase — that is, a small molecule that binds to the enzyme and increases its activity. By so doing, BIA 28-6156 is expected to prevent misfolded proteins from building up and damaging nerve cells.
Holenz said Bial has high hopes for its therapy candidate.
“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,” Holenz said.
The ACTIVATE study enrolled patients who had a diagnosis of Parkinson’s for at least one year, but for no longer than seven years. Eligible patients were on stable treatment for Parkinson’s for at least 30 days before screening, which will be maintained during the study.
Participants in the study were randomly assigned to receive a placebo or one of the two doses of BIA 28-6156 for up to 78 weeks. The main goal of the study is to watch for changes in the time from the beginning of the study to clinically meaningful progression of motor symptoms using the MDS-Unified Parkinson’s Disease Rating Scale parts 2 and 3.
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