Valbenazine Shows Sustained Treatment Effect on Huntington’s Chorea in KINECT-HD2 Open-Label Data

Newly presented interim data from KINECT-HD2 (NCT04400331), an open-label extension study assessing valbenazine (Ingrezza; Neurocrine Biosciences) in patients with Huntington disease (HD) chorea, showed that once-daily treatment with the medication was safe and effective, with clinically meaningful impacts seen for up to 1 year. Overall, these preliminary analyses indicated that the clinical profile of valbenazine is similar irrespective of background antipsychotic therapy.^1,2

Valbenazine was originally approved for patients with tardive dyskinesia in 2017, and later had its label expanded in 2023 to include the treatment of chorea associated with HD. Its approval was based on data from the phase 3 KINECT-HD study (NCT04102579) and its open-label extension, KINECT-HD2. The new data, presented at the 2024 International Congress of Parkinson’s Disease and Movement Disorders, held September 27 to October 1, in Philadelphia, Pennsylvania, comprised of 125 patients with HD who had received at least 1 dose of valbenazine at the time of the pre-planned interim analysis.

Led by principal investigator Erin Furr Stimming, MD, FAAN, FANA, a professor of neurology at McGovern Medical School of UTHealth Houston, improvements in Total Maximal Score (TMC) on the Unified Huntington’s Disease Rating Scale were observed as early as week 2 on the initial valbenazine dose of 40 mg (–3.4 [±3.1]; n = 118). These improvements were seen and sustained from week 8 (–5.6 [±3.6]; n = 110) to week 50 (–5.8 [±4.1]; n = 66) at doses up to 80 mg. These improvements were consistent regardless of presence or absence of concomitant antipsychotic treatment.

"The data from this study reinforce the long-term clinical safety of INGREZZA observed to date, showing sustained improvement in chorea regardless of antipsychotic use during the study," Eiry W. Roberts, MD, chief medical officer at Neurocrine, said in a statement.¹ "This is an important finding given that approximately a third of patients living with Huntington's disease chorea are prescribed antipsychotic medications for neuropsychiatric symptoms without receiving treatment for the chorea that may significantly disrupt daily life.”

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For context, the mean TMC score was 11.9 (±3.5) at baseline. Among those already receiving antipsychotic treatment, the improvements in TMC score did not appear to differ, as recorded on week 4 (–6.0 [±1.3]; n = 5) and week 50 (–5.2 [±2.2]; n = 5). Of the 125 participants in the pre-planned analysis, 119 (95.2%) reported at least 1 treatment-emergent adverse event (TEAE), and 17 (13.6%) discontinued because of a TEAE. The most common TEAEs were falls (30.4%), fatigue (24.0%), and somnolence (24.0%).

KINECT-HD2 was similar to the original KINECT-HD trial in that it featured adults aged 18 of 75 years who had been diagnosed with either manifest HD or motor manifest HD who had sufficient chorea symptoms. In KINECT-HD, valbenazine met its primary end point, demonstrating a statistically significant placebo-adjusted reduction in UHDRS TMC score of 3.2 units (P <.0001) from baseline to weeks 10 and 12.³

Additional data from the original study showed that treatment with valbenazine resulted in improved chorea as early as 2 weeks after administration in the lowest study dose (40 mg), with consistently greater improvement relative to placebo in all subsequent visits (weeks 4 to 12), as the dose was adjusted from 40 mg to 60 mg to 80 mg over the 12-week period. The study also met its secondary end points on change in Clinical Global Impression-Clinician (CGI-C) and Patient Global Impression-Clinician (PGI-C).By the end of the 12-week period, 43% and 53% of patients on valbenazine were classified as "much improved" or "very much improved" on CGI-C and PGI-C, respectively, compared with rates of 13% and 26% for those on placebo. Notably, the change in Neuro-QoL Upper Extremity Function T-score was not statistically significant after 12 weeks.

Earlier this year, the FDA approved a new sprinkle formulation of valbenazine to allow for greater administration options and flexibility. The oral granule capsules (40 mg, 60 mg, and 80 mg) are intended to be opened for sprinkling on soft foods prior to administration. The new drug application (NDA) filing for the sprinkle formulation included chemistry, manufacturing, and controls information and data demonstrating the bioequivalence and tolerability of the oral granule sprinkle capsules compared with the currently approved valbenazine capsules.⁴

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REFERENCES
1. Neurocrine Biosciences Presents Interim Data Demonstrating Robust and Sustained Improvements in Chorea Associated With Huntington's Disease Through Week 104 Irrespective of Antipsychotic Use. News release. Neurocrine Biosciences. September 30, 2024. Accessed October 3, 2024.
2. Furr Stimming E, Claassen D, Kayson E, et al. Sustained chorea improvements with long-term, once-daily valbenazine in adults with Huntington’s disease. Presented at: 2024 MDS Congress; September 27-October 1; Philadelphia, PA. ABSTRACT 1465
3. Stimming EF, Claassen DO, Kayson E, et al. Safety and efficacy of valbenazine for the treatment of chorea associated with Huntington’s disease (KINECT-HD): a phase 3, randomized, double-blind, placebo-controlled trial. Lancet Neurol. 2023;22:494-504
4. Neurocrine Biosciences Announces U.S. FDA Approval of INGREZZA® SPRINKLE (valbenazine) Capsules. News release. Neurocrine. April 30, 2024. Accessed October 3, 2024. https://www.prnewswire.com/news-releases/neurocrine-biosciences-announces-us-fda-approval-of-ingrezza-sprinkle-valbenazine-capsules-302132283.html