Parkinson Agent Solengepras Enters Phase 3, Sage to Discontinue SAGE-718, Serious Adverse Event Reported in Gene Therapy Study of NGN-401

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Welcome to this special edition of Neurology News Network. I'm Marco Meglio.

According to an announcement, Cerevance’s phase 3 ARISE pivotal trial (NCT06553027) assessing its investigational agent solengepras as a potential adjunctive therapy for Parkinson disease (PD) has begun dosing. The global, placebo-controlled, 12-week trial plans to enroll 330 patients with the disease, with topline data expected in the first half of 2026.Eligible participants for this study include individuals diagnosed with PD meeting UK Brain Bank and MDS Research Criteria, displaying bradykinesia, motor asymmetry, or rest tremor, and a prominent response to levodopa. The double-blind study will use change in the total daily OFF time over the 12-week period as the primary end point. Solengepras, also known as CVN424, is designed to selectively address the indirect dopamine pathway by modulating the GPR6 receptor.

Recent topline results from Sage Therapeutics’ 12-week, double-blind, placebo-controlled phase 2 DIMENSION study (NCT05107128) of SAGE-718, also known as dalzanemdor, showed that the treatment did not meet primary or secondary end points in patients with cognitive impairment (CI) associated with Huntington Disease (HD). Based on these findings, the company does not plan to further develop the agent and is also closing the ongoing phase 3 PURVIEW trial (NCT05655520), an open-label safety study in participants with HD.Among the 189 participants in DIMENSION study, SAGE-718 failed to demonstrate a statistically significant difference versus the placebo from baseline to day 84 on the primary end point of change in the Symbol Digit Modalities Test (SDMT). Additional analyzes of the secondary end points also did not reveal statistically significant or clinically meaningful differences in those treated with dalzanemdor compared with placebo. Despite this, the therapy was generally well-tolerated and had no new safety signals observed, with the majority of treatment emergent adverse events (TEAEs) reported as mild to moderate in severity.

In a company update, Neurogene announced that a trial participant in its phase 1 study (NCT05898620) had experienced an emerging treatment-related serious adverse event (SAE) with high dose of NGN-401, an investigational adeno-associated viral (AAV) gene therapy for Rett syndrome. The participant developed systemic hyperinflammatory syndrome, is currently in critical condition, and the situation is ongoing, according to the company.Thus far, there have been no other treatment-related SAEs in the clinical trial, including the 5 patients who received the 1E15 vg dose (low-dose cohort) and the 2 patients in the 3E15 vg dose (high-dose cohort). Neurogene had conversations with the FDA about the SAE through the START program, and ultimately, the company decided to pause further use of the high-dose cohort upon initial notification of the SAE and does not intend to enroll any additional participants at that dose level going forward.

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