Incidence of Adverse Events Associated With Deutetrabenazine for the Treatment of Tardive Dyskinesia and Chorea Associated With Huntington’s Disease (4416)

Objective: To evaluate the safety of deutetrabenazine in treating tardive dyskinesia (TD) and chorea associated with Huntington’s disease (HD).

Background: Deutetrabenazine is FDA-approved to treat TD in adults and HD chorea. In TD patients, deutetrabenazine showed significant improvements in motor function with a favorable safety profile in two 12-week pivotal trials, ARM-TD and AIM-TD, and the 3-year open-label extension (OLE) study. In HD patients, deutetrabenazine treatment significantly reduced chorea in the 12-week pivotal First-HD trial with a favorable safety profile, which continued in the long-term OLE trial, ARC-HD.

Design/Methods: Safety was assessed by comparing incidence of adverse events (AEs) with deutetrabenazine versus placebo. For TD, safety data were integrated from the 2 pivotal studies and through Week 15 of the OLE study. Data were analyzed by dose (12mg/day [n=72], 24mg/day [n=72], 36mg/day [n=72], flexible-dose [n=168], and placebo [pooled; n=130]). For HD, safety data were integrated upon first exposure to deutetrabenazine from First-HD and through Week 15 of ARC-HD for rollover patients who previously received placebo in First-HD. Safety data for deutetrabenazine (n=84) in the integrated analysis were compared with the placebo arm in First-HD (n=45).

Results: For TD, AEs with deutetrabenazine (all doses) and placebo (pooled), respectively, were: any, 44.4–59.5% and 53.8%; serious, 2.8–8.3% and 6.9%; treatment-related, 15.3–38.1% and 30.8%; and leading to withdrawal, 2.8–5.6% and 3.1%; and leading to dose reduction, 0–8.3% and 2.3%. For HD, AEs with deutetrabenazine and placebo, respectively, were: any, 64.3% and 60.0%; serious, 2.4% and 2.2%; treatment-related, 38.1% and 26.7%; leading to withdrawal, 1.2% and 2.2%; and leading to dose reduction, 7.1% and 6.7%.

Conclusions: Deutetrabenazine, the only FDA-approved vesicular monoamine transporter 2 inhibitor for multiple indications, was generally safe and well tolerated over 12–15 weeks of exposure compared to placebo in patients with TD and HD chorea.

Disclosure: Ms. Anderson has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for teva. Ms. Anderson has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Lundbeck. Ms. Anderson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AskBio. Ms. Anderson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for novartis. Ms. Anderson has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for neurocrine. Ms. Anderson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Medical Learning Istitute. Ms. Anderson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Medscape. Ms. Anderson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for atheneum. Ms. Anderson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for GLG. Ms. Anderson has received personal compensation in the range of $500-$4,999 for serving as a scientific advisor with CHDI. Dr. Fernandez has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Dr. Fernandez has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cerevel. Dr. Fernandez has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acorda. The institution of Dr. Fernandez has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sunovion. Dr. Fernandez has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Kyowa Hakko Kirin. Dr. Fernandez has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Partners Healthcare System. Dr. Fernandez has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Parkinson Study Group. Dr. Fernandez has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bial Neurology/Neurocrine. Dr. Fernandez has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biopas. Dr. Fernandez has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. The institution of Dr. Fernandez has received research support from Alkahest. The institution of Dr. Fernandez has received research support from Biogen. Dr. Fernandez has received research support from Michael J Fox Founda. The institution of Dr. Fernandez has received research support from Amneal. The institution of Dr. Fernandez has received research support from Teva Neurosciences. Dr. Frank has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Oscine Therapeutics. Dr. Frank has received personal compensation in the range of $500-$4,999 for serving as a Consultant for uniQure. Dr. Frank has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MCG Health. The institution of Dr. Frank has received research support from Huntington’s Disease Society of America. The institution of Dr. Frank has received research support from Michael J Fox Foundation. The institution of Dr. Frank has received research support from Roche/Genentech. The institution of Dr. Frank has received research support from CHDI Foundation. The institution of Dr. Frank has received research support from Huntington Study Group. The institution of Dr. Frank has received research support from Triplet Therapeutics. Dr. Factor has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acadia. Dr. Factor has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Impel. Dr. Factor has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Acorda. Dr. Factor has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CereSpir. Dr. Factor has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lundbeck. Dr. Factor has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. The institution of Dr. Factor has received research support from Impax. The institution of Dr. Factor has received research support from Lilly. The institution of Dr. Factor has received research support from Sunovion. The institution of Dr. Factor has received research support from Vaccinex. The institution of Dr. Factor has received research support from Voyager. The institution of Dr. Factor has received research support from Jazz Pharma. Dr. Factor has received publishing royalties from a publication relating to health care. Dr. Factor has received publishing royalties from a publication relating to health care. Dr. Factor has received publishing royalties from a publication relating to health care. Dr. Factor has received publishing royalties from a publication relating to health care. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Acadia Pharmaceuticals. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Acorda Therapeutics. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Adamas Pharmaceuticals. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Affiris. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AlphaSights. Dr. Hauser has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Amneal Pharmaceuticals. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ApoPharma. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Aptinyx. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Aranca. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Axovant. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Britannia. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Cadent. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for CAVR. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ClearView Healthcare Partners. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Clinical Score LLC. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for CNS Ratings LLC. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Compass Group. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Decision Resource Group (DRG). Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Dedham Group. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Defined Health. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Denali. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Enterin. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Extera Partners. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for FirstWord. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Global Kinetics Consulting (GKC). Dr. Hauser has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for GuidePoint Global. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Huron. Dr. Hauser has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Impax Laboratories. Dr. Hauser has received personal compensation in the range of $0-$499 for serving as a Consultant for InSearch Consulting. Dr. Hauser has received personal compensation in the range of $0-$499 for serving as a Consultant for Insignia Strategies. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Intrance Medical Systems. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for IQVIA. Dr. Hauser has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Jazz Pharmaceuticals. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Kaiser Permanente. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Kashiv Pharma. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for KeiferRX LLC. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for KeyQuest. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for KX Advisors. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Kyowa Kirin Pharmaceuticals. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for L.E.K. Consulting. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Lundbeck A/S. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medscape. Dr. Hauser has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for MPTA. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NeuroChallenge Foundation for PD. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Neurocrine Biosciences. Dr. Hauser has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for NeuroDerm. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NOVUS. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Orion. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Parkinson Study Group. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pennside Partners. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Perception OpCo (Cerevel Therapeutics LLC). Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Regenera Pharma. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ROCHE . Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Schlesinger Associates. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Scion Neurostim LLC. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Seelos Therapeutics. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Slingshot Insights. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sunovion Pharmaceuticals. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Teva Pharmaceuticals. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Tolmar Inc.. Dr. Hauser has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for US World Meds. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pharmather. Dr. Hauser has received personal compensation in the range of $0-$499 for serving as a Consultant for Global Life Sciences. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Revance Therapeutics. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Supernus Pharma. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Inhibikase. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for LifeSciences Consultants. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Research Catalyst . Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Curium Pharma. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Inhibikase. Dr. Hauser has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Impel Neuro Pharma. Dr. Hauser has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cerespir. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Acorda Therapeutics. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Adamas Pharmaceuticals. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Amneal Pharmaceuticals. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Kyowa Kirin Pharmaceuticals. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Neurocrine Biosciences. Dr. Hauser has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Sunovion Pharmaceuticals, Inc.. Dr. Hauser has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for US World Meds. Dr. Hauser has received stock or an ownership interest from Inhibikase. Dr. Hauser has received stock or an ownership interest from Axial Therapeutics. The institution of Dr. Hauser has received research support from Biogen, Inc.. The institution of Dr. Hauser has received research support from Biotie Therapies, Inc.. The institution of Dr. Hauser has received research support from Cavion, Inc. The institution of Dr. Hauser has received research support from Centogene. The institution of Dr. Hauser has received research support from Cerevel. The institution of Dr. Hauser has received research support from Civitas Therapeutics, Inc.. The institution of Dr. Hauser has received research support from Cynapsus Therapeutics. The institution of Dr. Hauser has received research support from Enterin. The institution of Dr. Hauser has received research support from Global Kinetics Corporation. The institution of Dr. Hauser has received research support from Impax Laboratory. The institution of Dr. Hauser has received research support from Intec Pharma. The institution of Dr. Hauser has received research support from Jazz Pharmaceuticals, Inc.. The institution of Dr. Hauser has received research support from Neuro Derm. The institution of Dr. Hauser has received research support from Northwestern University. The institution of Dr. Hauser has received research support from Pfizer. The institution of Dr. Hauser has received research support from Pharma 2 B. The institution of Dr. Hauser has received research support from Revance Therapeutics. The institution of Dr. Hauser has received research support from Roche. The institution of Dr. Hauser has received research support from Sun Pharma Advanced Research. The institution of Dr. Hauser has received research support from Sunovion. The institution of Dr. Hauser has received research support from AbbVie. The institution of Dr. Hauser has received research support from Axovant Sciences Ltd.. The institution of Dr. Hauser has received research support from Cerevance. The institution of Dr. Hauser has received research support from MJFF. The institution of Dr. Hauser has received research support from Neuraly. The institution of Dr. Hauser has received research support from Sanofi US Services, Inc.. Dr. Hauser has received intellectual property interests from a discovery or technology relating to health care. Dr. Jimenez Shahed has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Nuvelution. Dr. Jimenez Shahed has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Bracket Global LLC. Dr. Jimenez Shahed has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for St. Jude Medical, Inc. Dr. Jimenez Shahed has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Boston Scientific. Dr. Jimenez Shahed has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Teva. Dr. Jimenez Shahed has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Revance. Dr. Jimenez Shahed has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amneal. Dr. Jimenez Shahed has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Impel. Dr. Jimenez Shahed has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medtronic. The institution of Dr. Jimenez Shahed has received research support from Michael J Fox Foundation. The institution of Dr. Jimenez Shahed has received research support from Teva. The institution of Dr. Jimenez Shahed has received research support from Lily. The institution of Dr. Jimenez Shahed has received research support from Wilson Therapeutics. Dr. Jimenez Shahed has received personal compensation in the range of $500-$4,999 for serving as a Faculty with Movement Disorders Society. Dr. Jimenez Shahed has received personal compensation in the range of $500-$4,999 for serving as a Faculty with David Phinney Foundation. Dr. Jimenez Shahed has received personal compensation in the range of $500-$4,999 for serving as a Faculty with American Academy of Neurology. Dr. Jimenez Shahed has received personal compensation in the range of $500-$4,999 for serving as a Faculty with WebMD. Dr. Jimenez Shahed has received personal compensation in the range of $500-$4,999 for serving as a Grant Reviewer with Parkinson Foundation. Dr. Jimenez Shahed has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant on Research Grant with Florida Atlantic University. Hadas Barkay has received personal compensation for serving as an employee of Teva Pharmaceuticals. Amanda Wilhelm has received personal compensation for serving as an employee of Teva Pharmaceuticals. Jessica K. Alexander has received personal compensation for serving as an employee of Teva Pharmaceuticals. Jessica K. Alexander has received stock or an ownership interest from Teva Pharmaceuticals. Nayla Chaijale has received personal compensation for serving as an employee of Teva Pharmaceuticals. Alexander Send has received personal compensation for serving as an employee of Teva Pharmaceuticals. Alexander Send has received stock or an ownership interest from Teva Pharmaceuticals. Juha-Matti Savola has nothing to disclose. Dr. Stamler has received personal compensation for serving as an employee of Alterity Therapeutics. Dr. Gordon has received personal compensation for serving as an employee of Teva. Dr. Gordon has received stock or an ownership interest from Teva. Maria Chen has received personal compensation for serving as an employee of Teva Pharmaceuticals.