FDA Accepts Supplemental NDA for Valbenazine as Therapy for Huntington Disease Chorea

The phase 3 KINECT-HD study, which showed statistically significant differences from placebo in Total Maximal Chorea score, served as one of the main parts to valbenazine’s supplemental new drug application.

Eiry W. Roberts, MD, chief medical officer, Neurocrine Biosciences

Eiry W. Roberts, MD

According to a recent announcement, the FDA has accepted Neurocrine Biosciences’ supplemental new drug application (sNDA) for valbenazine (Ingrezza), a selective vesicular monoamine transporter 2 (VMAT2) inhibitor, as a treatment for chorea associated with Huntington disease (HD). The agency is expected to make a decision on the agent by August 20, 2023.1

The sNDA is supported by findings from the double-blind, placebo-controlled, phase 3 KINECT-HD study (NCT04102579) and the ongoing open-label KINECT-HD2 study (NCT04400331). Each study features adults aged 18 to 75 years of age who have been diagnosed with either manifest HD or motor manifest HD who have sufficient chorea symptoms.

Eiry W. Roberts, MD, chief medical officer, Neurocrine Biosciences, said in a statement, “This sNDA filing advances our effort to bring a potential new treatment option to the many thousands of people experiencing chorea associated with Huntington disease in the U.S. We look forward to working with the FDA as it reviews our filing."1

In KINECT-HD, a total of 128 patients with HD were randomly assigned 1:1 to either valbenazine or placebo for a 12-week treatment period, with the first 8 weeks being dose-adjusted followed by a 4-week maintenance phase. At the conclusion of the trial, the agent met its primary end point, represented by a statistically significant placebo-adjusted reduction in the Unified Huntington’s Disease Rating Scale (UHDRS) Total Maximal Chorea (TMC) score of 3.2 units (P <.00001) from baseline to weeks 10 and 12.2

On secondary end points, investigators observed reductions of 42.9% and 52.7%, respectively, on Clinical Global Impression of Change and Patient Global Impression of Change in valbenazine-treated patients vs reductions of 13.2% (P <.001) and 26.4% (P <.01) for those on placebo. Quality of Life in Neurological Disorders scale, another secondary end point used to assess upper and lower extremity function, was included in the study but did not reach statistical significance.

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Treatment-emergent adverse events (TEAEs) were found in 76.6% of those on valbenazine and 63.5% of those on placebo, with serious TEAEs reported in 1.6% and 3.2% of those groups, respectively. The most common TEAEs, which included somnolence, fatigue, fall, and akathisia, were mild to moderate in nature and consistent with prior safety findings. Notably, no patients demonstrated suicidal behavior or suicidal ideation while on the study drug.

KINECT-HD2, the open-label study, includes approximately 150 adults with motor manifest HD who are assessed for up to 156 weeks. Similar to KINECT-HD, this study uses change from baseline to maintenance in the UHDRS TMC score as the primary end point. Still recruiting, that study will span across a study period of 104 weeks.

In April 2017, history was made as valbenazine became the first FDA-approved treatment for patients with TD. Later that year, a capsule strength form of the medication also gained greenlight. The drug’s approval was based on more than 20 clinical studies that included over 1000 individuals. Data from these studies showed that 80-mg valbenazine provided significant, rapid, and meaningful improvement in TD severity compared to placebo at 6 weeks (–3.2 vs –0.1; ≤.001) with separation seen as early as 2 weeks, and continued reductions recorded through 48 weeks of treatment.3

REFERENCES
1. Neurocrine Biosciences announces US FDA accepts supplemental new drug application for valbenazine as a treatment for chorea associated with Huntington disease. News release. Neurocrine Biosciences. December 22, 2022. Accessed January 23, 2023. https://www.prnewswire.com/news-releases/neurocrine-biosciences-announces-us-fda-accepts-supplemental-new-drug-application-for-valbenazine-as-a-treatment-for-chorea-associated-with-huntington-disease-301709335.html
2. Neurocrine Biosciences Presents Additional Phase 3 Data for KINECT-HD Study Evaluating Valbenazine for Chorea Associated with Huntington Disease at HSG 2022. News release. Neurocrine. November 3, 2022. Accessed January 23, 2023. https://www.prnewswire.com/news-releases/neurocrine-biosciences-presents-additional-phase-3-data-for-kinect-hd-study-evaluating-valbenazine-for-chorea-associated-with-huntington-disease-at-hsg-2022-301666869.html
3. Neurocrine announces FDA approval of 80 mg ingrezza® (valbenazine) capsules for the treatment of adults with tardive dyskinesia. News release. Neurocrine Biosciences. October 5, 2017. Accessed January 23, 2022. https://www.prnewswire.com/news-releases/neurocrine-announces-fda-approval-of-80-mg-ingrezza-valbenazine-capsules-for-the-treatment-of-adults-with-tardive-dyskinesia-td-300531471.html
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