Fast onset of action with valbenazine for treatment of chorea associated with Huntington disease
Presenter: Raja Mehanna, MD, University of Texas Health Science Center, Houston, TX
Indirect treatment comparison of valbenazine with deutetrabenazine for improvement in total maximal chorea score in Huntington disease. Abstract 890. Presented August 29, 2023.
An indirect comparison of data from clinical trials in adults with chorea associated with Huntington disease (HD) showed that valbenazine improves chorea as early as week 2 and has a therapeutic effect similar to deutetrabenazine during the maintenance phase.
Valbenazine and deutetrabenazine are both vesicular monoamine transporter 2 inhibitors. Deutetrabenazine is currently approved by the US Food and Drug Administration (FDA) for the treatment of chorea associated with HD, and valbenazine is currently under FDA review for this indication. In the phase 3 trials of valbenazine (KINECT-HD)1 and deutetrabenazine (First-HD) that this study compared,2 improvements in chorea were significantly greater with active treatment versus placebo. However, there is no available trial that compared the efficacy of deutetrabenazine and valbenazine in the treatment of chorea associated with HD, noted the investigators, led by Raja Mehanna, MD, University of Texas Health Science Center, Houston, TX.
To assess the relative efficacy of valbenazine versus deutetrabenazine for chorea associated with HD, Mehanna and colleagues used the Bucher indirect treatment comparison method3 to assess data from those phase 3 clinical trials. “Given their similar study designs and patient populations, KINECT-HD and First-HD were ideal candidates for performing an indirect treatment comparison analysis,” they wrote in their poster presentation, in which preliminary results were presented, with a more comprehensive analysis to come.
Both KINECT-HD and First-HD were 12-week clinical trials that used the Unified Huntington’s Disease Rating Scale (UHDRS) and total maximal chorea (TMC) score to evaluate the effects of treatment on chorea in adults with HD.
The KINECT-HD trial had an 8-week dose-adjustment period during which valbenazine capsules were administered once daily up to a target dosage of 80 mg/day, which was maintained during the 4-week maintenance phase. In First-HD, deutetrabenazine tablets (6 mg, 9 mg, or 12 mg) were administered twice daily and escalated weekly in 6-mg increments, per the FDA-approved dosing recommendation, with a target daily dosage of 48 mg/day.
The analyses presented included participants who had available UHDRS TMC assessments at screening, baseline, and after at least 1 post-baseline visit. Analyses were conducted using mean changes in UHDRS TMC score from screening/baseline (average of screening and baseline scores) at weeks 2, 4, 6, and study endpoint.
The TMC score changes from screening/baseline favored valbenazine over deutetrabenazine and reached statistical significance at week 2 (with initial 40-mg dose for valbenazine) and week 4. The mean difference between valbenazine and deutetrabenazine in TMC score change from screening/baseline favored valbenazine by 1.87 points at week 2 and 1.84 points at week 4 (P < 0.05 for both). Although TMC scores at week 6 and during the maintenance period numerically favored valbenazine over deutetrabenazine, statistical significance was not achieved.
The investigators concluded: “Results of these analyses indicate that improvements in HD-associated chorea were significantly greater with valbenazine versus deutetrabenazine during early treatment (ie, at weeks 2 and 4) and were similar to deutetrabenazine at later timepoints (ie, at week 6 and endpoint). The 2- to 4-week timeframe of this study suggests that the corresponding doses of valbenazine (40 and 60 mg, respectively) may be sufficient for reducing chorea in some patients with HD. In contrast, a 2- to 4-week timeframe might not be sufficient for patients to reach an efficacious dose with deutetrabenazine.”
References
- Furr Stimming E, Claassen DO, Kayson E, et al. Safety and efficacy of valbenazine for the treatment of chorea associated with Huntington's disease (KINECT-HD): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Neurol 2023; 22(6):494-504. doi: 10.1016/S1474-4422(23)00127-8.
- Huntington Study Group; Frank S, Testa CM, Stamler D, et al. Effect of deutetrabenazine on chorea among patients with Huntington disease: a randomized clinical trial. JAMA 2016; 316(1):40-50. doi: 10.1001/jama.2016.8655.
- Bucher HC, Guyatt GH, Griffith LE, Walter SD. The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials. J Clin Epidemiol 1997; 50(6):683-691. doi: 10.1016/s0895-4356(97)00049-8.
Disclosure
This study was supported by Neurocrine Biosciences, Inc, San Diego, CA. Writing assistance and editorial support were provided by Prescott Medical Communications Group, Inc, Chicago.