Early interim data from Gain Therapeutics’ Phase 1b study of GT-02287 in Parkinson’s disease point to stability and improvements on MDS-UPDRS motor and activities-of-daily-living measures at Day 90 among the first nine participants, with similar trends reported in several of the first 21 patients overall. Mean baseline MDS-UPDRS scores were 5.8 (Part I), 7.4 (Part II), and 24.7 (Part III). Improvements emerged at Day 90, not Day 30; Part I remained stable. Pharmacokinetics in 14 sampled participants were consistent and within the projected therapeutic range, aligning with exposures seen in the prior healthy volunteer study. Safety was acceptable with no treatment-emergent serious adverse events; transient liver enzyme elevations resolved despite ongoing dosing. Two independent DMC reviews recommended continuation, and Australian regulators cleared an extension enabling up to 12 months of treatment.
The company presented the poster at the International Congress of Parkinson’s Disease and Movement Disorders, summarizing safety (primary endpoint) and exploratory clinical observations in people with and without GBA1 mutations. The open-label trial enrolled 21 participants across seven Australian sites, reflecting a real-world mix: two treatment-naïve, two with deep brain stimulation, and most on levodopa and/or dopamine agonists. Regulators’ approval of a 12‑month extension positions the program to collect durability data beyond the initial 90-day dosing window.
Strategically, Gain is leaning into a pharmacologic restoration of glucocerebrosidase activity via an allosteric small molecule intended to address lysosomal dysfunction across GBA1-mutated and idiopathic PD. That positioning aims to avoid the operational and regulatory complexity of gene therapy and the mixed track record of substrate reduction approaches. The appearance of a functional signal over 90 days—while far from confirmatory—helps de-risk dose selection and supports a move toward a randomized design. However, the absence of a control arm, small sample size, and known placebo effects in PD underscore the need for longer, blinded assessment and biomarker corroboration to credibly argue disease modification.
For sites and CROs, the extension approval shifts operational planning toward retention, longitudinal scheduling, centralized ratings, and routine hepatic monitoring given observed transient enzyme elevations. The heterogeneity of concomitant therapies, including DBS, will necessitate tight stratification and rater calibration to limit noise in motor outcomes. Sponsors and vendors should anticipate demand for objective biomarker integration—CSF or peripheral GCase activity and neurofilament light chain—to link mechanism to clinical change and meet evolving regulatory expectations for disease-modifying claims. Competition for PD recruitment remains intense; an oral, add-on regimen could help enrollment, but GBA1 stratification and central read infrastructure will be critical.
Near term, watch for the full 90‑day dataset across all participants, responder distributions on MDS-UPDRS Parts II and III, and any accompanying biomarker readouts that bridge exposure, target engagement, and clinical effect. The 12‑month extension will be the first test of durability and trajectory separation from natural history, which will inform whether the next study should be GBA1-enriched or broadly idiopathic. Key risks include the interpretability of open-label outcomes, potential liver signal management as exposure increases in longer dosing, and operational complexity over a one-year horizon. An update on Phase 2 design—control strategy, enrichment, and biomarker endpoints—will clarify the regulatory path and the program’s ability to differentiate in a crowded PD pipeline. A company KOL event on October 14 may provide additional context on these choices.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
