Higher doses of deutetrabenazine appear to be safe and well tolerated in patients with Huntington disease who may require them to adequately control chorea, according to a recently published post-hoc analysis.
Deutetrabenazine, a vesicular monoamine transporter 2 (VMAT2) inhibitor, is currently approved by the Food and Drug Administration (FDA) for the treatment of chorea associated with Huntington disease at a maximum dose of 48mg/day. To investigate the long-term safety and efficacy of the treatment, an open-label extension study (ARC-HD) was conducted and dosages between 6mg/day and 72mg/day were assessed. Patients received dose increases in a response-driven manner up to 48mg/day, after which, further increases (12mg/day per week) were permitted at the investigator’s discretion to a maximum of 72mg/day.
“In this post-hoc analysis, patient counts and safety assessments were attributed to patients when they received a dose either ≤48mg/day or >48mg/day,” the study authors reported. Adverse event (AE) rates were compared for 9 selected AEs (ie, akathisia, depression, fall, anxiety, dysphagia, parkinsonism, somnolence, insomnia, suicidality) and were adjusted for drug exposure duration.
Among the 113 patients in the study, only 49 received doses greater than 48mg/day (74.1 patient-years). Results showed that following the titration phase, there appeared to be no difference in the rate of exposure-adjusted AEs when comparing patients receiving deutetrabenazine doses less than or equal to 48mg/day to those receiving doses greater than 48mg/day.
Based on their findings, the study authors concluded that doses >48mg/day were well tolerated and were not associated with increases in the rates of selected AEs. “This analysis does not address the occurrence of other AEs or whether adequate efficacy was achieved at lower doses, factors that may have influenced dose increases,” they added.
Frank S, Vaughan C, Stamler D, et al. Evaluation of the safety of deutetrabenazine at higher doses to treat chorea in huntington’s disease. Neurology. Apr 2020, 94 (15 Supplement) 4310.