Abstract Details

Title 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

Topic Movement Disorders

Presentation(s) P8 - Poster Session 8 (8:00 AM-9:00 AM)

Poster/Presentation
Number 3-013

Objective Assess safety, pharmacokinetics (PK), and pharmacodynamics of oral venglustat, a glucosylceramide (GL-1) synthase inhibitor, in Parkinson’s disease (PD) patients with a glucocerebrosidase (GBA) mutation from Japan and the rest of the world (ROW).

Background GBA mutations predispose PD patients to cognitive impairment and rapid disease progression at a younger age.

Design/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/placebo was administered for up to 36 weeks in the ROW population and 52 weeks in Japanese patients (evaluated separately per regulatory agency request). Assessments: venglustat safety/tolerability (primary endpoint); plasma and cerebrospinal fluid (CSF) PK and pharmacodynamics.

Results Twenty-nine 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). Eight (89%) Japanese venglustat-treated patients and 12 (92%) ROW patients reported ≥1 adverse event (AE) versus 2 (67%) and 4 (100%) from the respective placebo groups; most AEs were mild/moderate. Psychiatric, gastrointestinal, and neurological events, consistent with common motor/non-motor PD symptoms or known AEs of concurrent PD medications, were most frequent in both populations. No serious AEs/deaths occurred. No Japanese patients and 2 venglustat-treated ROW patients discontinued due to AEs after Week 4 (primary timepoint). In both populations, venglustat exposure in plasma and CSF increased in a close to dose-proportional manner; 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/tolerability in Japanese and ROW PD patients, with dose-dependent plasma and CSF exposure, and reduction in plasma and CSF GL-1.

Authors/Disclosures
M. Judith Peterschmitt, MD (Sanofi) PRESENTER	No disclosure on file
Hidemoto Saiki, MD (Parkinson's Disease advanced therapy center, Aichi Medical University)	No disclosure on file
Taku Hatano, MD (Department of Neurology Juntendo University School of Medicine)	Dr. Hatano has nothing to disclose.
	No disclosure on file
Stuart H. Isaacson, MD, F�鶹��ýӳ�� (Parkinson's Dis & Mov Dis Ctr of Boca Raton)	The institution of Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Acadia. The institution of Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sunovion. The institution of Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for acorda. The institution of Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Supernus. The institution of Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Neurocrine. The institution of Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Kyowa. The institution of Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for adamas. The institution of Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Lundbeck. The institution of Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Teva. The institution of Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Neuroderm. The institution of Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Abbvie. The institution of Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for amneal. Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Teva. Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Neurocrine. Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for adamas. Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Lundbeck. Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Supernus. Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Acadia. Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Acorda. Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Amneal. Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Abbvie.
Jaime Kulisevsky, MD, PhD (Sant Pau Hospital)	Dr. Kulisevsky has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Esteve. Dr. Kulisevsky has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Britannia. Dr. Kulisevsky has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AC Immune. Dr. Kulisevsky has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bial. Dr. Kulisevsky has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Zambon. Dr. Kulisevsky has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Britannia.
Tanya Simuni, MD, F�鶹��ýӳ�� (Northwestern University Feinberg School of Medicien)	Dr. Simuni has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for cadia, AcureX, Adamas, AskBio, Amneal, Blue Rock Therapeutics, Caraway Therapeutics, Critical Path for Parkinson's Consortium (CPP), Denali, Michael J Fox Foundation, Neuroderm, Sanofi, Sinopia, Roche, Takeda and Vanqua Bio. Dr. Simuni has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for of Koneksa, Neuroderm, Sanofi, UCB, AcureX, Adamas, AskBio, Biohaven, Denali, GAIN, Neuron23 and Roche. Dr. Simuni has received research support from Amneal, Biogen, Neuroderm, Prevail, Roche, and UCB and an investigator for NINDS, MJFF, Parkinson's Foundation.
Yuji Takahashi, MD, PhD (National Center of Neurology and Psychiatry)	The institution of Dr. Takahashi has received research support from Nihon Medi-Physics Co. Limit.. The institution of Dr. Takahashi has received research support from Takeda Pharmaceutical Company Limited.
Hector Gonzalez	Hector Gonzalez has nothing to disclose.
	No disclosure on file
	No disclosure on file
Ryosuke Takahashi, MD (Kyoto University Graduate School of Medicine)	Dr. Takahashi has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Kan Institute. Dr. Takahashi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Takeda Pharma. Dr. Takahashi has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Ono Pharma. Dr. Takahashi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Kyowa Kirin Pharma. Dr. Takahashi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Otsuka Pharma. Dr. Takahashi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Abbvie. Dr. Takahashi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eisai. Dr. Takahashi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Chugai Pharma. Dr. Takahashi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Takahashi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Argenix. Dr. Takahashi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alnyrum. Dr. Takahashi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sumitomo Pharma. The institution of Dr. Takahashi has received research support from MEXT. Japan. The institution of Dr. Takahashi has received research support from AMED, Japan. The institution of Dr. Takahashi has received research support from JST, Japan. The institution of Dr. Takahashi has received research support from MHLW, Japan. The institution of Dr. Takahashi has received research support from Sumitomo Pharma. The institution of Dr. Takahashi has received research support from Takeda Pharma. The institution of Dr. Takahashi has received research support from Otsuka Pharma. Dr. Takahashi has received personal compensation in the range of $500-$4,999 for serving as a PO with AMED, Japan. Dr. Takahashi has received personal compensation in the range of $500-$4,999 for serving as a PO with JST, Japan.
Cheryl H. Waters, MD, F�鶹��ýӳ�� (Columbia University)	Dr. Waters has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Acadia. Dr. Waters has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Kyowa. Dr. Waters has received personal compensation in the range of $500-$4,999 for serving as a Consultant for US world meds. Dr. Waters has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexza. Dr. Waters has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Acorda. Dr. Waters has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Acadia. Dr. Waters has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Neurocrine. Dr. Waters has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bial. Dr. Waters has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for US world meds. Dr. Waters has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Lundbeck. Dr. Waters has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Adamas. Dr. Waters has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sunovion. Dr. Waters has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Amneal.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
S. Pablo Sardi, PhD (SANOFI)	Dr. Sardi has received personal compensation for serving as an employee of Sanofi. The institution of Dr. Sardi has received research support from MJFF.
Stephane Saubadu, MD	Dr. Saubadu has received personal compensation for serving as an employee of Sanofi. Dr. Saubadu has stock in Sanofi.
	No disclosure on file
Tanya Fischer, MD, PhD	No disclosure on file

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