Similar to the double-blind study, valbenazine was well-tolerated with clinically meaningful improvement in chorea severity after nearly a year of treatment.
Months after the FDA approved valbenazine (Ingrezza; Neurocrine Biosciences) for the treatment of chorea associated with Huntington disease (HD), new interim data from the open-label extension (OLE) of the phase 3 KINECT-HD2 study (NCT04400331) continued to highlight the therapy’s longterm efficacy and safety. All told, improvements in chorea were observed at the first evaluation (week 2) when participants were taking the lowest dose of 40 mg, with efficacy sustained through week 50 at a maximal dose of 80 mg.1,2
After the completion of the phase 3 KINECT-HD study, adults with genetically confirmed motor-manifest HD entered the OLE where they received once-daily valbenazine starting at 40 mg for up to 156 weeks. In addition to safety evaluations, efficacy outcomes included change in Unified Huntington’s Disease Rating Scale Total Maximal (TMC) score, Clinical Global Impression of Change (CGI-C), and Patient Global Impression of Change (PGI-C). The data, which included outcomes up to week 50, were presented at the 30th Annual Meeting of the Huntington Study Group, held November 2-4, in Phoenix, Arizona.
Of 127 participants at the time of the analysis, 98 were from KINECT-HD. All told, mean TMC score reductions were observed by week 2 with valbenazine 40 mg (n = 118; –3.4 [±3.1]) and sustained with maximal doses of 80 mg from week 8 (n = 110; 5.6 [±3.6]) to week 50 (n = 66; –5.8 [±4.1]). At week 50, 76.9% (50 of 65) of participants were CGI-C responders and 74.2% (49 of 66) were PGI-C responders. Among 125 patients who received treatment, 95.2% (n = 119) reported at least 1 treatment-emergent adverse event (TEAE) and 13.6% (n = 17) discontinued because of a TEAE. Falls (30.4%), fatigue (24.0%), and somnolence (24.0%) were among the most common TEAEs reported.
"These interim data provide insight on the clinically meaningful and sustained improvements participants are experiencing with INGREZZA for the treatment of chorea," Eiry W. Roberts, MD, chief medical officer at Neurocrine Biosciences, said in a statement. “We look forward to analyzing additional data as they become available."
Neurocrine also presented new substudy data from KINECT-HD using a wearable movement sensor, the first such study of its kind. Using the BioStamp nPoint system, participants wore 3 sensors (chest and anterior thighs) for 2, 7-day periods during the screening period and following the week 10 visit. A total of 27 patients (valbenazine: n = 12; placebo: n = 15) who wore the sensors for at least 5 hrs/day for at least 5 days during baseline and maintenance were included in the analysis. Results showed significant improvements in truncal chorea and gait asymmetry measures in the valbenazine (all P <.05) but not in the placebo group. Of note, 6 participants reported any sensor-related AE, all of which were mild.3
Valbenazine, a selective vesicular monoamine transporter 2 inhibitor, became the first such inhibitor FDA-approved for the treatment of chorea associated with HD in August 2023 based on results from the phase 3 KINECT-HD study and its OLE, KINECT-HD2. Similar in design, each study featured adults aged 18 to 75 years who had been diagnosed with either manifest HD or motor manifest HD who have sufficient chorea symptoms. In KINECT-HD, the agent met its primary end point, demonstrating a statistically significant placebo-adjusted reduction in Total Maximal Chorea (TMC) score of 3.2 units (P <.00001) from baseline to weeks 10 and 12.4