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.
"Interim data results from the KINECT-HD2 open-label study suggest one-capsule, once-daily valbenazine improved chorea at the first evaluation at week 2 when participants were taking the initial dose of 40 mg, with efficacy sustained through week 50 at most 80 mg," Eiry W. Roberts, MD, chief medical officer at Neurocrine Biosciences, told NeurologyLive®. "More than half of participants and investigators rated symptoms as 'much improved' or 'very much improved' at week 6, and about 3-quarters of participants and investigators rated symptoms as 'much improved' or 'very much improved' by week 50. The most common treatment-emergent adverse events at the time of the analysis were consistent with those observed in the phase 3 KINECT-HD study, including falls, fatigue and somnolence."
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
"We are pleased with the interim data results from KINECT-HD2 and remain focused on the continuation of this ongoing open-label study to investigate the long-term safety and tolerability of valbenazine in patients with HD chorea. We look forward to analyzing and providing updates on additional data when available. Additionally, Neurocrine continues to engage with the scientific community on what the data from the studies, including KINECT-HD and KINECT-HD2, can tell us about the potential benefits of valbenazine for treatment of patients with HD chorea in clinical practice," Roberts told.
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
"The clinical results of the KINECT-HD phase 3 study that led to the FDA approval of valbenazine for chorea associated with HD showed reduction in the severity of chorea as early as two weeks after starting valbenazine at an initial dose of 40 mg, with consistently greater improvements versus placebo seen at all subsequent visits through the end of the 12-week study. The 50-week data from the ongoing KINECT-HD2 study demonstrate clinically meaningful and sustained improvement in reducing chorea. These data provide insight into the potential long-term use of valbenazine for the management of chorea associated with HD," Roberts told.