GZ/SAR402691

[LordJim]

Anyone else in the GBA Parkinson's trial for GlaxoSolveys GZ/SAR402671?

They seem to be ending the trial with no explanation.

[sharoncrayn]

GBA is a gene mutation theory of PD causation. Hypothetically, it or the variations encompass at least 5% of the US PD population.

Sanofi-Genzyme started a Phase 2 with their drug GZ/SAR402671. CT known as MOVES-PD was to be done in 2 phases. Multi-center. Long term.

Started CT in 2016.

Primary completion is sometime late 2020

Final Completion date is 2024 (estimate)

Nice, France September 22-26, 2019-Late Breaking Abstracts

Safety, Pharmacokinetics, and Pharmacodynamics of Oral Venglustat in the Japanese and the Rest of the World Parkinson’s Disease Population with a GBA Mutation: Results from Part 1 of the MOVES-PD Study

Objective: To assess the safety, pharmacokinetics (PK), and pharmacodynamics of oral venglustat in Parkinson’s disease (PD) patients with a glucocerebrosidase (GBA) mutation from Japan and the rest of the world (ROW).

Background: A heterozygous mutation in GBA predisposes PD patients to cognitive impairment and rapid disease progression at a younger age [1]. Venglustat is a glucosylceramide (GL-1) synthase inhibitor investigated in PD patients with a GBA mutation.

Methods: Part 1 of the phase 2 MOVES-PD trial (NCT02906020) was a randomized, placebo-controlled, double-blind, sequential cohort study of venglustat at 3 escalating doses in PD patients ≥18 years with a GBA mutation. Venglustat doses were evaluated separately in Japanese patients (per regulatory agency request) to ensure consistency with ROW population. Venglustat/placebo was administered for up to 36 weeks in ROW population and 52 weeks in Japanese patients. Assessments: venglustat safety/tolerability (primary endpoint); plasma and cerebrospinal fluid (CSF) PK and pharmacodynamics.

Results: A total of 29 PD patients were randomized to venglustat (Japan [n=9]; ROW [n=13]) or placebo (Japan [n=3]; ROW [n=4]). Mean age was 54.3 years (Japan) and 58.4 years (ROW); mean time since

PD symptom onset was 6.7 years, and since diagnosis was 5.2 years in both populations. Eight (89%) Japanese venglustat-treated patients, and 12 (92%) ROW patients reported ≥1 treatment-emergent AE (TEAE) versus 2 (67%) and 4 (100%) patients from the respective placebo groups; most TEAEs were mild/moderate and resolved without corrective treatment. Psychiatric, gastrointestinal, and neurological events, consistent with common motor/non-motor PD symptoms or known AEs of concurrent PD International Congress of Parkinson’s Disease and Movement Disorders®medications, were the most common TEAEs in both populations. No serious AEs or deaths occurred. No Japanese patients and 2 ROW patients on venglustat discontinued due to TEAEs after Week 4 (primary timepoint). In both populations, venglustat exposure in plasma and CSF increased in a close to doseproportional manner, and plasma and CSF GL-1 levels decreased from baseline in a dose-dependent manner over 4 weeks. At the highest dose, CSF GL-1 decreased 72.0% in Japanese and 74.3% in ROW patients.

Conclusions: All doses of venglustat demonstrated favorable safety and tolerability in Japanese and ROW PD patients, with dose-dependent plasma and CSF exposure, and reduction in plasma and CSF GL-1.

Part 2 of MOVES-PD is ongoing.

References: 1. Cilia R, Tunesi S, Marotta G, et al. Survival and Dementia in GBA-associated Parkinson’s Disease: The Mutation Matters. Ann Neurol. 2016; 80: 662–673.

Sharon

[sharoncrayn in reply to sharoncrayn]

Part 2 of MOVES-PD is ongoing.