Valbenazine Shows Positive Phase 3 Results in Treating Chorea in Huntington Disease

SAP Partner | <b>NYU Langone Health</b>

Patients treated with valbenazine demonstrated favorable outcomes on all secondary outcomes over placebo, as well showed no new safety signals.

Newly published topline results from the phase 3 KINECT-HD study (NCT04102579) showed that once-daily treatment with valbenazine (Ingrezza; Neurocrine Biosciences), a selective vesicular monoamine transporter 2 (VMAT2) inhibitor, reduces the severity of chorea in patients with Huntington disease (HD). Neurocrine noted that data from this study will be presented at a medical conference in 2022.1

Valbenazine, an FDA-approved medication for tardive dyskinesia (TD), met its primary end point in the placebo-controlled trial, 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.

"The positive results of the KINECT-HD study move us closer to bringing valbenazine as a potential treatment option to patients in the U.S. living with chorea, one of the most common symptoms of Huntington disease," Eiry W. Roberts, MD, chief medical officer, Neurocrine Biosciences, said in a statement.1 "We will review the complete data and begin preparing a supplemental new drug application (sNDA) for submission to the US Food and Drug Administration next year. In the meantime, we will continue dosing in the KINECT-HD2 study, which is evaluating the long-term safety and tolerability of valbenazine in this same patient population."

A total of 128 patients with HD, aged 18 to 75 years old, were randomized 1:1 to either valbenzaine or placebo for 12 weeks. The first 8 weeks of the study were a dose adjustment period followed by a dose maintenance phase for 4 weeks. During this period, patients who did not tolerate the drug well were allowed to have dosage lowered by a clinical investigator.

At the end of the treatment period, valbenazine showed a consistent safety profile, with no new treatment-emergent adverse events observed during the trial. Notably, no patients demonstrated suicidal behavior or suicidal ideation while on study drug. Compared with placebo, patients that received valbenazine also showed favorable responses on secondary end points including Clinical Global Impression of Change (CGI-C) Response Status and Patient Global Impression of Change (PGI-C) Response Status.

"We are energized by these positive data and grateful to have been part of a study that has advanced a potential new therapy for people living with chorea associated with Huntington disease," Andrew Feigin, MD, chair, Huntington Study Group, and professor, Department of Neurology, NYU Grossman School of Medicine, said in a statement.1 "We look forward to continuing our work with Neurocrine Biosciences through the KINECT-HD2 study and working toward our goal of benefiting the lives of those living with this condition."

There is an open-label study–KINECT-HD2 (NCT04400331)–that looks to evaluate the long-term safety and tolerability of the valbenazine in a similar cohort of 150 adults; however, patients in this trial will have motor manifest HD. Still recruiting, this study will assess number of TEAEs, as well as change from baseline in UHDRS TMC score, 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; P ≤.001) with separation seen as early as 2 weeks, and continued reductions recorded through 48 weeks of treatment.2

REFERENCES
1. Neurocrine Biosciences announces positive phase 3 data for KINECT-HD study evaluating valbenazine for chorea associated with Huntington disease. News release. Neurocrine Biosciences. December 7, 2021. Accessed January 6, 2022. https://www.prnewswire.com/news-releases/neurocrine-biosciences-announces-positive-phase-3-data-for-kinect-hd-study-evaluating-valbenazine-for-chorea-associated-with-huntington-disease-301439605.html
2. 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 6, 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