Abstract Details

Title Effect Sizes of Once-daily Valbenazine for Chorea Associated with Huntington’s Disease: A Post-hoc Analysis of KINECT®-HD Data

Topic Movement Disorders

Presentation(s) P10 - Poster Session 10 (5:00 PM-6:00 PM)

Poster/Presentation
Number 5-012

Objective To assess treatment effect sizes of once-daily valbenazine for chorea associated with Huntington’s disease (HD).

Background Once-daily valbenazine is approved for chorea associated with HD and tardive dyskinesia. Cohen’s d effect sizes, which describe standardized differences between two means (e.g., mean score changes between placebo and active drug in a clinical trial), are used to compare the magnitude of effects across studies or therapies and can be interpreted as small (0.2-<0.5), medium (0.5-<0.8), or large (≥0.8). Effect sizes reported for common neurologic treatments include levodopa for Parkinson’s disease (0.9), sumatriptan for migraines (0.8), methylphenidate for attention-deficit/hyperactivity disorder (0.8), and memantine for moderate-to-severe Alzheimer’s disease (0.3 to 0.5).

Design/Methods Cohen’s d effect sizes for valbenazine in HD chorea were calculated using Unified Huntington’s Disease Rating Scale (UHDRS®) Total Maximal Chorea (TMC) data from KINECT®-HD (NCT04102579), a 12-week phase 3 study of valbenazine (≤80 mg) versus placebo. Effect sizes were calculated at all post-baseline study visits and at maintenance (average of Week 10 and Week 12 scores) using the difference between valbenazine and placebo for the mean TMC score change from screening/baseline (average of screening and baseline scores) divided by the pooled standard deviation.

Results

The least squares mean changes from screening/baseline to maintenance in TMC score were -4.6 and -1.4 for valbenazine and placebo, respectively. The placebo-corrected improvement (i.e., least squares mean difference [LSMD] between treatment groups) was -3.2 (P<0.0001 [primary endpoint]). The effect size increased from Week 2 (d=0.5), when all participants were taking the initial 40-mg dose, to a large effect (d=0.9) at maintenance, with 81.8% taking the target 80-mg dose at Week 12.

Conclusions Based on TMC data from KINECT-HD, meaningful effect sizes were detected as early as Week 2 at the initial 40-mg dose. Effect sizes for valbenazine generally increased throughout the 12-week trial to a large effect size at maintenance.

Authors/Disclosures
Sean Hinton, PhD (Neurocrine Biosciences) PRESENTER	Dr. Hinton has received personal compensation for serving as an employee of Neurocrine Biosciences, Inc. Dr. Hinton has stock in Neurocrine Biosciences, Inc..
Raja Mehanna, MD (University of Texas Health Science Center At Houston-McGovern Medical School)	Dr. Mehanna has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Teva. Dr. Mehanna has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Kyowa Kirin. The institution of Dr. Mehanna has received research support from Cerevel. The institution of Dr. Mehanna has received research support from Neurocrine.
Erin Furr-Stimming, MD, FAAN (University of Texas Health Science Center-Houston)	Dr. Furr-Stimming has received personal compensation for serving as an employee of Help4HD International. Dr. Furr-Stimming has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medscape. Dr. Furr-Stimming has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MedPage. Dr. Furr-Stimming has received personal compensation in the range of $500-$4,999 for serving as a Consultant for PTC Therapeutics. Dr. Furr-Stimming has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Wave Life Sciences. Dr. Furr-Stimming has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Latus Bio. Dr. Furr-Stimming has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Atalanta Therapeutics. Dr. Furr-Stimming has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Furr-Stimming has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for SkyHawk Therapeutics. Dr. Furr-Stimming has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis . Dr. Furr-Stimming has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Atalanta Therapeutics. The institution of Dr. Furr-Stimming has received research support from Roche/Genetech. The institution of Dr. Furr-Stimming has received research support from Uniqure. The institution of Dr. Furr-Stimming has received research support from CHDI. The institution of Dr. Furr-Stimming has received research support from Huntington Study Group/Neurocrine Bioscienes. The institution of Dr. Furr-Stimming has received research support from NIH/University of Iowa. The institution of Dr. Furr-Stimming has received research support from Sage Therapeutics. The institution of Dr. Furr-Stimming has received research support from HDSA. The institution of Dr. Furr-Stimming has received research support from Prilennia. Dr. Furr-Stimming has received publishing royalties from a publication relating to health care. Dr. Furr-Stimming has received publishing royalties from a publication relating to health care. Dr. Furr-Stimming has a non-compensated relationship as a Committee member with AAN UES Committee that is relevant to AAN interests or activities.
Elise Kayson, NP	Ms. Kayson has nothing to disclose.
Jody Goldstein, BS	Miss Goldstein has nothing to disclose.
Olga Klepitskaya, MD, FAAN (Neurocrine Biosciences, Inc)	Dr. Klepitskaya has received personal compensation for serving as an employee of Neurocrine Biosciences, Inc. Dr. Klepitskaya has or had stock in Neurocrine Biosciences.
Hui Zhang (Neurocrine Bioscience)	Hui Zhang has received personal compensation for serving as an employee of Neurocrine Bioscience Inc..
Eduardo Dunayevich, MD	Eduardo Dunayevich has received personal compensation for serving as an employee of Neurocrine Biosciences. Eduardo Dunayevich has stock in Neurocrine Biosciences.
Grace L. Liang, MD	Dr. Liang has received personal compensation for serving as an employee of Neurocrine Biosciences. Dr. Liang has stock in Neurocrine Biosciences.
Dietrich Haubenberger, MD, FAAN (Neurocrine Biosciences)	Dr. Haubenberger has received personal compensation for serving as an employee of Neurocrine Biosciences, Inc. Dr. Haubenberger has stock in Neurocrine Biosciences. Dr. Haubenberger has a non-compensated relationship as a Member of the Board with American Society for Experimental Neurotherapeutics that is relevant to AAN interests or activities.

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