Pariceract Fails to Meet Primary End point in Phase 2b ACTIVATE Trial for GBA1-Associated Parkinson Disease

Based on newly reported topline results, Bial has decided to discontinue development of pariceract for patients with GBA1-associated (GBA) Parkinson disease (PD) after the investigational therapy failed to meet primary and key secondary efficacy end points in the phase 2b ACTIVATE study (NCT05819359). The company noted that detailed findings from the ACTIVATE study are planned for presentation at scientific conferences and publication in peer-reviewed journals.¹

ACTIVATE was a multinational phase 2b study evaluating the efficacy, safety, tolerability, pharmacodynamics, and pharmacokinetics of pariceract in patients with genetically confirmed GBA-PD. The trial enrolled participants over approximately 18 months across 85 clinical sites in 11 countries throughout Europe and North America. Among 273 patients eith GBA-PD, findings showed that treatment with pariceract did not significantly slow disease progression compared with placebo; however, the therapy was generally well tolerated, with no unexpected safety concerns reported.

“We are disappointed with the outcome of the Phase 2b ACTIVATE study, as the results do not confirm the hypothesis under investigation. I would like to express our gratitude to the study participants, their families and caregivers, the investigators, all the sites involved, and our teams for making this trial possible. We remain committed to finding treatments that could change disease progression for people living with Parkinson’s,” António Portela, Chief Executive Officer of Bial, said in a statement.¹

Pariceract was being developed as a first-in-class, orally administered allosteric activator of beta-glucocerebrosidase (GCase), the lysosomal enzyme encoded by GBA1. Reduced GCase activity is believed to contribute to lysosomal dysfunction and α-synuclein accumulation, mechanisms implicated in PD pathogenesis. Because GBA1 mutations represent one of the strongest known genetic risk factors for PD, therapies targeting GCase have attracted significant interest as potential disease-modifying approaches.²

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Development of pariceract was supported by earlier clinical data demonstrating target engagement and favorable safety findings. In a phase 1b randomized, placebo-controlled study, pariceract demonstrated safety when orally administered daily for 28 days among patients with GBA-PD.³ Notably, findings showed that pharmacologically active plasma and cerebrospinal fluid (CSF) concentrations were reached and intracellular GluCer elevations were identified.

This phase 1 randomized, double-blind, placebo-controlled trial included 40 participants with GBA-PD who were administered 28 consecutive daily doses of 10, 30, or 60 mg of pariceract, or placebo. The levels of glycosphingolipid (glucosylceramide and lactosylceramide) were measured in peripheral blood mononuclear cells, plasma, and CSF. Researchers also conducted a test battery of neurocognitive tasks as well as assessed the participants with Movement Disorder Society - Unified Parkinson's Disease Rating Scale and the Mini-Mental State Exam.

There were no deaths or treatment-related serious adverse effects reported using the therapy, and no participants dropped out of the study because of adverse events. Additionally, findings displayed that Cmax, and an area under the curve (AUC) 0-6 of pariceract increased in a dose-proportional manner, showing free CSF concentrations equal to the free fraction in plasma.

“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. We will use these findings to inform the community and to accelerate our efforts to develop new therapeutic solutions in this indication,” Joerg Holenz, Chief Scientific Officer of Bial, said in a statement.¹

REFERENCES
1. Bial Reports Topline Results From ACTIVATE Phase 2b Study in GBA‑Associated Parkinson’s. News release. Bial. June 9, 2026. Accessed June 11, 2026. https://www.bial.com/en/media/news/bial-reports-topline-results-from-activate-phase-2b-study-in-gba-associated-parkinsons
2. Gan-Or Z, Liong C, Alcalay RN. GBA-Associated Parkinson's Disease and Other Synucleinopathies. Curr Neurol Neurosci Rep. 2018;18(8):44. Published 2018 Jun 8. doi:10.1007/s11910-018-0860-4
3. den Heijer JM, Kruithof AC, Moerland M, et al. A Phase 1B Trial in GBA1-Associated Parkinson's Disease of BIA-28-6156, a Glucocerebrosidase Activator. Mov Disord. 2023;38(7):1197-1208. doi:10.1002/mds.29346