Neurocrine Biosciences Submits Supplemental NDA for Valbenazine in the Treatment of Huntington Disease Chorea

Eiry W. Roberts, MD

In a recent announcement of a data presentation from the phase 3 KINECT-HD study (NCT04102579) of valbenazine (Ingrezza; Neurocrine Biosciences) at the 29th annual meeting of the Huntington Study Group, held from November 3-5, 2022, in Tampa, Florida, the company’s chief medical officer noted that these data—as well as findings from the ongoing open-label KINECT-HD2 study (NCT04400331)—served as the basis for the supplemental new drug application (sNDA) for the therapy in the treatment of chorea associated with Huntington disease (HD).¹

Previously, in May 2022, the company announced that valbenazine had received an orphan drug designation from the FDA.² Topline data of the selective vesicular monoamine transporter 2 (VMAT2) inhibitor from KINECT-HD were presented in December 2021.³

The poster data showed that valbenazine, which is approved in the US for the treatment of tardive dyskinesia, met its primary end point. Ultimately, at week 12, the placebo-adjusted least-squares mean change with valbenazine was a reduction of 3.2 units on the Total Maximal Chorea score (P <.0001).

On secondary end points of Clinical Global Impression of Change and Patient Global Impression of Change, there were reductions of 42.9% and 52.7%, respectively, with valbenazine compared with 13.2% (P <.001) and 26.4% (P <.01) for those on placebo. Additional secondary end point data included change on the Quality of Life in Neurological Disorders scale for upper and lower extremity function, though these measures did not reach statistical significance.

Notably, enrollment in the long-term KINECT-HD2 study is still ongoing, with a target of 158 individuals. Neurocrine’s chief medical officer, Eiry W. Roberts, MD, said in a statement that "the additional findings of the phase 3 KINECT-HD study presented in this poster demonstrate an improvement in chorea over time, with an increase in responder rates in the [Total Maximal Chorea score] primary end point, and [Clinical Global Impression of Change] and [Patient Global Impression of Change] outcomes by study visit up to week 12.”¹

As for safety, the incidence of treatment emergent adverse events (TEAEs), including somnolence, fatigue, fall, and akathisia, were mild to moderate in nature and deemed to be consistent with prior safety findings. The incidence of any TEAE was 76.6% with valbenazine and 63.5% with placebo, while serious TEAEs were reported by 1.6% of those on valbenazine and 3.2% of those on placebo. Treatment discontinuation because of TEAEs occurred for 7.8% and 6.3% of valbenazine-treated and placebo patients, respectively. There were no instances of suicidal behavior or worsening of suicidal ideation observed in the valbenazine-treated subjects in KINECT-HD.

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 in KINECT-HD. 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.

REFERENCES
1. 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 November 4, 2022. 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
2. Neurocrine Biosciences Receives Orphan Drug Designation for Valbenazine as a Treatment for Chorea Associated with Huntington Disease. News release. Neurocrine. May 12, 2022. Accessed November 4, 2022. https://www.prnewswire.com/news-releases/neurocrine-biosciences-receives-orphan-drug-designation-for-valbenazine-as-a-treatment-for-chorea-associated-with-huntington-disease-301546658.html
3. Neurocrine Biosciences announces positive phase 3 data for KINECT-HD study evaluating valbenazine for chorea associated with Huntington disease. News release. Neurocrine. December 7, 2021. Accessed November 4, 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