Valbenazine Eases Chorea in Trial; FDA Submission Expected Next Year
Treatment with valbenazine significantly lessened chorea — a motor symptom characterized by jerky, unpredictable, and involuntary movements — in people with Huntington’s disease in the Phase 3 clinical trial KINECT-HD, according to an announcement from the therapy’s developer, Neurocrine Biosciences.
Neurocrine now is planning to submit an application next year asking the U.S. Food and Drug Administration (FDA) to approve valbenazine to treat Huntington’s-associated chorea.
“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, Neurocrine’s chief medical officer, said in a press release.
“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,” added Andrew Feigin, MD, chair of the Huntington Study Group, a clinical research network that helped to run the KINECT-HD trial.
KINECT-HD (NCT04102579) enrolled 128 adults with Huntington’s, ages 18 to 75, who had marked chorea symptoms. The participants were randomly assigned to receive either valbenazine or a placebo, taken once daily for 12 weeks, or about three months.
The trial’s main goal was to assess the effect of treatment on the Total Maximal Chorea or TMC score from the Unified Huntington’s Disease Rating Scale (UHDRS), a standard measure of this motor symptom that assesses chorea in seven body parts — the face, mouth/jaw, trunk, and each limb.
Results showed that, compared with a placebo, valbenazine reduced the TMC score by 3.2 units on average — which represents “a highly statistically significant improvement in chorea,” according to Neurocrine. Specifically, the therapy significantly reduced chorea movements, the company said.
Changes in the Clinical Global Impression of Change (CGI-C) and the Patient Global Impression of Change (PGI-C) — respectively, clinician- and patient-reported measures of disease severity — also showed a significant improvement with valbenazine over the placebo.
Safety results were in line with the known safety profile of valbenazine. Importantly, none of the participants exhibited suicidal behavior or worsening suicidal ideation, a known side effect of the medication, the company said.
“We are incredibly grateful to the KINECT-HD participants for contributing [to] the success of this important clinical trial,” said Erin Furr-Stimming, MD, a professor at McGovern Medical at UTHealth Houston, in Texas, and the trial’s principal investigator.
Neurocrine and the Huntington Study Group are now running an extension trial called KINECT-HD2 (NCT04400331), in which all participants will be treated with valbenazine. KINECT-HD2 is enrolling patients who participated in the original KINECT-HD study, and also about 30 new participants. Enrollment is ongoing at numerous locations in North America.
Based on the data from KINECT-HD, Neurocrine is planning to submit a supplemental new drug application (sNDA) to the FDA next year requesting approval of valbenazine for chorea in Huntington’s. Full results from the trial also will be presented at a conference 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,” Roberts said.
“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,” Feigin added.
Valbenazine works by blocking the activity of vesicular monoamine transporter-2 (VMAT-2), a protein that controls the activity of dopamine in the brain. Dopamine is a signaling molecule that is important for coordinating movement; valbenazine aims to lessen involuntary movements by lowering the amount of dopamine available in the brain. It currently is FDA-approved to treat a movement disorder called tardive dyskinesia, for which it is marketed under the brand name Ingrezza.