Opicapone

Portugal-based Bial reported that pariceract (BIA 28-6156; formerly LTI-291, LTI-00291), its oral small-molecule allosteric activator of beta-glucocerebrosidase (GCase), failed to slow disease progression in patients with GBA1 gene-associated Parkinson’s disease, ending development of what had been one of the few mechanism-specific candidates in this genetically defined population. The result closes a program that had enrolled 273 patients across 85 sites in Europe and North America, and deals a further setback to the GCase activation hypothesis in GBA-associated Parkinson’s disease — a subtype affecting an estimated 5%-15% of all Parkinson’s patients and typically characterized by faster motor progression and earlier cognitive decline than idiopathic disease. The ACTIVATE trial was a Phase IIb, multicenter, randomized, double-blind, placebo-controlled study evaluating pariceract in genetically confirmed GBA-PD patients across two fixed oral doses (10 mg/day and 60 mg/day). Enrollment of 273 patients took approximately 18 months, with sites spanning 11 countries. The study assessed efficacy, safety, tolerability, pharmacodynamics, and pharmacokinetics. Bial announced the first patient to complete the full dose regimen in January 2025, with topline data expected mid-2026. Neither the primary endpoint nor the key secondary efficacy endpoints were met. Bial did not disclose the specific primary endpoint measure or numerical efficacy data in the topline release, stating only that pariceract “failed to slow the progression of GBA-PD versus placebo”. The drug was reported as generally well tolerated, with no unexpected safety concerns identified — a finding that does not rescue the program but may inform future mechanistic work in the field. Based on the absence of demonstrated efficacy, Bial has discontinued further development of pariceract for this indication. Competitive context The GCase activation space has now accumulated two high-profile clinical failures in rapid succession. In May 2026, Biogen (Nasdaq: BIIB) and Denali Therapeutics (Nasdaq: DNLI) reported that BIIB122 (DNL151), a small-molecule LRRK2 inhibitor, failed its Phase IIb LUMA study in early-stage idiopathic Parkinson’s disease — a different target but another genetically informed disease-modification strategy that did not translate into clinical benefit. While the LUMA failure involved a distinct mechanism and broader patient population, it reinforces the difficulty of demonstrating disease modification in Parkinson’s with current trial designs and endpoints. Within the GCase space specifically, competitors remain active at earlier stages. Maryland-based Gain Therapeutics (Nasdaq: GANX) is advancing GT-02287, a GCase allosteric modulator, in a Phase Ib extension study in patients with Parkinson’s disease with or without a GBA1 mutation. Interim data presented in May 2026 showed stable MDS-UPDRS scores over 150 days and a differential response pattern in patients with elevated baseline cerebrospinal fluid glucosylsphingosine, a GCase substrate biomarker — though the study was not designed to assess clinical efficacy. Chicago-based Vanqua Bio reported Phase Ib data in March 2026 showing that VQ-101, another oral GCase activator, achieved greater than 50% activation of lysosomal GCase in GBA-Parkinson’s patients, meeting a pre-specified target engagement goal. Both programs remain substantially earlier in development than pariceract was at the time of its failure. Cross-trial comparisons are limited by differences in patient populations, dose levels, trial duration, and endpoint selection, and the mechanistic success of earlier-stage programs does not predict Phase II outcomes. The pariceract result will prompt scrutiny of whether GCase target engagement alone — without demonstrated downstream effects on alpha-synuclein aggregation or neurodegeneration — is sufficient to support efficacy hypotheses in GBA-PD clinical trials. The failure also raises questions about trial design in this space. GBA-PD patients progress faster than idiopathic PD patients on average, which theoretically improves statistical power to detect disease modification over a given timeframe. Whether the ACTIVATE study was adequately powered, whether the doses selected achieved sufficient central nervous system GCase activation, and whether the primary endpoint was sensitive enough to detect clinically meaningful slowing will be central questions when Bial presents full data at scientific meetings. The company said it intends to disseminate the ACTIVATE data through peer-reviewed publications and conferences. For Bial, which invests over 20% of annual revenue in R\&D and has focused its neuroscience pipeline on Parkinson’s disease, the discontinuation removes what had been a lead disease-modification asset. The company’s approved portfolio includes opicapone (Ongentys), a COMT inhibitor used as adjunct therapy to levodopa in Parkinson’s patients with motor fluctuations — a symptomatic treatment that competes in a different segment of the disease management landscape. Pariceract had represented Bial’s attempt to move upstream toward disease modification in a genetically defined subpopulation, a strategy that now requires reassessment. This article was generated with AI assistance and reviewed and edited by the AllSci editorial team Explore more at AllSci News: https://allsci.com/news/ Your email address will not be published. Required fields are marked * Comment * Name * Email * Website Privacy Terms About Us Copyright © 2026. AllSci Corp. All rights reserved.

Study Topline results will be released around the end of Q2 2026 BIA 28-6156 is being developed as a potential first-in-class disease-modifying therapy in GBA-PD Bial was present at the GBA1 conference and is currently attending the World Parkinson Congress PORTO, Portugal--(BUSINESS WIRE)-- #BIA28 --Bial, an innovation-driven biopharmaceutical company focused on neurosciences and rare diseases, today announced the completion of the treatment period in its Phase 2b ACTIVATE study of BIA 28-6156 (pariceract) in patients with Parkinson’s disease (PD) who have a pathogenic mutation in the glucocerebrosidase 1 (GBA1) gene (GBA-PD). Upon completion of the 78-week double-blind treatment period and all scheduled safety follow-ups, data cleaning and analysis are currently ongoing. Topline results will be released around the end of Q2. A status report on the ACTIVATE study was presented in an oral presentation at the 3 rd International GBA1 Meeting 2026 . The team is currently attending the 7 th World Parkinson Congress , taking place in Phoenix from 24 to 27 May 2026. “Momentum is building across the Parkinson’s scientific community around the clinical potential of pariceract. At the GBA1 Meeting and the 7th World Parkinson Congress , we have been able to connect with this community as we approach a key milestone, the anticipated release of topline results from our ACTIVATE study," said Raquel Costa, Head of Clinical Operations and study lead. 273 genetically confirmed GBA-PD patients were enrolled over approximately 18 months across 85 clinical sites in 11 countries throughout Europe and North America. The study reported strong patient retention, reflecting the commitment of patients and study site teams. “This is a particularly exciting moment for the whole Parkinson’s community and for Bial. We would like to sincerely thank the patients, their families, investigators, and site teams who contributed to the ACTIVATE with extraordinary commitment and rigour over the course of the study. We are hopeful that BIA 28-6156 may help address a major unmet need by targeting the underlying cause of GBA1-associated Parkinson’s," added Raquel Costa. The ACTIVATE study is evaluating the efficacy, safety, tolerability, pharmacodynamics, and pharmacokinetics of BIA 28-6156 in patients with GBA-PD. BIA 28-6156 is in development as a first-in-class, small molecule for once-daily oral administration, allosteric activator of beta-glucocerebrosidase (GCase), for the treatment of patients with GBA-PD. By increasing the activity of GCase, BIA 28-6156 may be the first drug to directly modify the underlying cause of the disease in this group of patients by re-establishing the sphingolipid recycling. (1,2) Parkinson’s is the second most common neurodegenerative disorder, affecting more than 10 million people worldwide. (3) Between 5-15% of Parkinson’s patients have mutations in the GBA1 gene, making it the largest genetic risk factor. (4) GBA-PD patients tend to have, on average, an earlier onset of symptoms compared to those with idiopathic Parkinson’s (5) and have more severe clinical symptoms that progress significantly faster, leading to a worse overall prognosis, (4) thus emphasising the importance of developing new treatments for this condition. Translating Bial’s focus on Parkinson's Disease research and development, the company is also presenting two posters at the 7 th World Parkinson Congress, highlighting patient perspectives on treatment routines and adherence, and new insights from a Phase IV study on opicapone’s effects on sleep and non-motor symptoms in Parkinson’s. Posters Details: Date: 26 May 2026 Session Time: 11:30 AM - 1:00 PM Location: Room: Hall D-E (3rd floor) - Phoenix Convention Center Posters Title: TRACK-PD: Understanding Treatment Routines and Adherence in Care - Knowledge and Perspectives of People Living with Parkinson’s Disease Effect of Opicapone on Sleep-Related Complaints and Non-Motor Burden in Parkinson’s Patients: A Post-Hoc Analysis of the OASIS Trial About Bial Bial is an innovation-driven pharmaceutical company dedicated to improving the health and lives of people worldwide. With a strong commitment to therapeutic innovation, Bial has established an ambitious R&D programme, consistently investing over 20% of its annual revenue in this area. The company focuses on two key areas with high unmet medical needs: neurosciences and rare diseases. In Europe, Bial operates manufacturing facilities and a R&D centre at its headquarters in Portugal, and maintains affiliates in Spain, Germany, the United Kingdom, Italy, and Switzerland. In addition, Bial is present in the United States and selected emerging markets. As part of its international growth strategy, the company collaborates with established partners through strategic alliances and licensing agreements to expand access to its healthcare solutions. Currently, Bial’s products are available in more than 50 countries, advancing its mission to pursue scientific excellence, mainly in neurosciences and rare diseases, delivering transformative medicines that empower patients’ lives. For more information about BIA 28-6156, please visit: For more information about the trial design, please visit: (identifier: NCT05819359) For more information about Bial, please visit: References den Heijer JM et al. Br J Clin Pharmacol. 2021 Sep;87(9):3561-3573 Guedes L. et al. Integrated safety analysis of BIA-28-6156 phase 1 clinical trials (a novel allosteric activator of beta-glucocerebrosidase). Presented at the International Congress of Parkinson’s Disease and Movement Disorders (MDS), Copenhagen, Denmark. August 27–31, 2023 APDA, , accessed May 18 th 2026 Smith L, Schapira AHV. Cells. 2022 Apr 8;11(8):1261 Gan-Or Z, et al. Neurology. 2015 Mar 3;84(9):880-7 Contacts Media Contacts: Bial Susana Vasconcelos Director, Communication T. +351229866100 | E. susana.vasconcelos@bial.com