Trial of BIA 28-6156 for GBA1 Parkinson’s patients hits milestone
More than 80% of participants have completed one year of treatment
More than 80% of the people with Parkinson’s disease caused by GBA1 gene mutations who are enrolled in a Phase 2 clinical trial have completed one year of treatment with Bial’s experimental candidate BIA 28-6156.
The study, called ACTIVATE (NCT05819359), is assessing the treatment’s safety and efficacy at slowing the clinical progression of motor symptoms in people with Parkinson’s and GBA1 mutations compared with a placebo. Dosing was begun earlier this year, and about a quarter of the participants have completed the 1.5-year treatment period.
The last participant is expected to complete their final visit by April 2026, with top-line results anticipated by June.
“All patients reaching week 52 [year one] of the study is a highly meaningful milestone,” Raquel Costa, Bial’s head of clinical operations and study lead, said in a company press release. “This brings us closer to obtaining the data needed to rigorously assess the safety and efficacy of BIA 28-6156, which could become a much-needed disease-modifying treatment for this patient population.”
Mutations in GBA1 are a risk factor for developing Parkinson’s
Mutations in GBA1, the gene that provides instructions for producing the GCase enzyme, are a risk factor for developing Parkinson’s. When GCase is faulty or missing, toxic clumps of misfolded proteins accumulate around brain nerve cells, resulting in Parkinson’s symptoms.
People with GBA-related Parkinson’s, also known as GBA-PD, frequently have an earlier symptom onset, and symptoms are more severe and usually progress faster than in those without these mutations.
BIA 28-6156 is an orally available small molecule designed to bind to GCase and increase its activity. The treatment is therefore expected to prevent misfolded proteins from building up and damaging nerve cells, which Bial believes may make BIA 28-6156 the first drug to directly modify the disease’s underlying cause in this group of patients.
The Phase 2 ACTIVATE trial recruited 273 adults, ages 35 to 80, with GBA-PD across 85 sites in North America and Europe. Participants were randomly assigned to receive either 10 mg or 60 mg of BIA 28-6156 or a placebo once daily for 78 weeks, or about 1.5 years.
The trial’s main goal is to assess the time to clinically meaningful progression on motor aspects of experiences of daily living and motor signs of the disease, as assessed by parts 2 and 3 of the MDS-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS).
Changes in other measures of disease severity, including MDS-UPDRS total and motor scores, the Modified Hoehn and Yahr scale, and the Clinical and Patient Global Impression-Change scales, will also be assessed, as will health-related quality of life.
The company also recently presented a poster, titled “A 6-year longitudinal analysis from the Parkinson’s progression markers initiative on non-motor symptom severity and progression in GBA1-associated vs. sporadic Parkinson’s disease,” at the International Congress of Parkinson’s Disease and Movement Disorders, held recently in Honolulu, U.S.
The findings suggest nonmotor symptoms are more severe and progress more rapidly in Parkinson’s patients with GBA1 mutations than in those without them.
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