Venglustat nonsuperior to placebo after 1 year for GBA1-associated Parkinson’s disease

Key takeaways:

• A study included 221 adults with GBA1-associated Parkinson’s disease given 15 mg venglustat or placebo for 52 weeks.
• Venglustat was safe and well-tolerated but had no beneficial effect compared with placebo.

Although generally safe and well-tolerated, venglustat treatment for adults with GBA-1 associated Parkinson’s disease was not superior to placebo after 1 year, per data from the Lancet Neurology.

“No disease-modifying treatments have been approved for Parkinson’s disease, perhaps partly because drug development efforts have approached PD as a single entity,” Nir Giladi, MD, neurologist in the Movement Disorders Unit, Neurological Institute, Tel Aviv Sourasky Medical Center, and colleagues wrote.

In the MOVES-PD clinical trial, a randomized, double-blind, placebo-controlled study, Giladi and colleagues sought to assess safety, efficacy and target engagement of venglustat in adults with early-stage Parkinson’s disease who carry pathogenic GBA1 variants.

Part one of MOVES-PD established safety, efficacy and pharmacokinetics of venglustat at a dose of 15 mg; part two was a phase 2 clinical trial conducted at 52 locations (academic sites, specialty clinics and general neurology centers) in 16 countries. MOVES-PD part 2 included 221 individuals aged 18 to 80 years with Parkinson’s disease (Hoehn and Yahr stage 2) and one or more GBA1 variants randomized 1:1 to either 15 mg/day oral venglustat (n = 110) or placebo (n = 111) for 52 weeks, with or without food.

The primary outcome was change from baseline to 52 weeks in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) parts II and III combined score (where higher scores indicate greater impairment), analyzed in a modified intention-to-treat population (mITT).

According to results, mean change for the mITT in MDS-UPDRS parts II and III combined score was 7.29 for venglustat (n = 96) and 4.71 for placebo (n = 105); the absolute difference between groups was 2.58 (95% CI, –1.10 to 6.27).

The most common treatment-emergent adverse events (TEAEs) were constipation and nausea, with serious TEAEs logged for 12 participants in each group and one death recorded in the venglustat group due to an unrelated cardiopulmonary arrest.

“These findings suggest that glucosylveramide synthase inhibition with venglustat is not a viable therapeutic approach for people with GBA1-associated Parkinson’s disease,” Giladi and colleagues wrote.