Solengepras Enters Phase 3 for Parkinson's, SAGE-718 Discontinued, and Neurogene Pauses NGN-401 High-Dose Trial
核心洞察
Cerevance (搜索)'s solengepras (CVN424) has entered a Phase 3 trial (ARISE) as an adjunctive therapy for Parkinson's disease, with topline data expected in the first half of 2026.
Sage Therapeutics discontinued the development of SAGE-718 (dalzanemdor) for Huntington's disease after disappointing Phase 2 results showing no significant cognitive improvement.
Neurogene paused the high-dose arm of its Phase 1 study of NGN-401, a gene therapy for Rett syndrome (搜索), following a serious adverse event in one participant.
Cerevance (搜索) has initiated dosing in its Phase 3 ARISE trial (NCT06553027) to evaluate solengepras as an adjunctive treatment for Parkinson's disease. The global, placebo-controlled study aims to enroll 330 patients, with topline results anticipated in the first half of 2026. Solengepras, also known as CVN424, is designed to selectively modulate the GPR6 receptor (搜索), targeting the indirect dopamine pathway.
Solengepras Phase 3 Trial Details
Eligible participants include those diagnosed with Parkinson's disease based on UK Brain Bank and MDS Research Criteria, exhibiting bradykinesia, motor asymmetry, or rest tremor, and demonstrating a notable response to levodopa. The primary endpoint of the double-blind study is the change in total daily OFF time over the 12-week treatment period.
SAGE-718 Development Halted
Sage Therapeutics has discontinued the development of SAGE-718 (dalzanemdor) for Huntington's disease following topline results from the Phase 2 DIMENSION study (NCT05107128). The 12-week, double-blind, placebo-controlled trial failed to meet its primary or secondary endpoints in patients with cognitive impairment associated with Huntington's disease. The company is also closing the ongoing Phase 3 PURVIEW trial (NCT05655520), an open-label safety study.
In the DIMENSION study, SAGE-718 did not demonstrate a statistically significant difference compared to placebo from baseline to day 84 on the primary endpoint, the Symbol Digit Modalities Test (SDMT). Additional analyses of secondary endpoints also showed no significant or clinically meaningful differences. The therapy was generally well-tolerated, with most treatment-emergent adverse events reported as mild to moderate in severity. The study included 189 participants.
Neurogene Pauses NGN-401 High-Dose Cohort
Neurogene has announced a pause in the high-dose cohort of its Phase 1 study (NCT05898620) of NGN-401, an investigational adeno-associated viral (AAV) gene therapy for Rett syndrome (搜索). This decision follows a treatment-related serious adverse event (SAE) in one participant receiving the high dose. The participant developed systemic hyperinflammatory syndrome and is in critical condition.
To date, no other treatment-related SAEs have been reported in the clinical trial, including the five patients who received the low dose (1E15 vg) and the two patients in the high-dose cohort (3E15 vg). Neurogene has consulted with the FDA through the START program and decided to halt further use of the high-dose cohort. No additional participants will be enrolled at that dose level.