For patients who rolled over to the ARC-HD extension study from the previous First-HD trial, there was a 4.5-point reduction in mean chorea scores at week 8 that were maintained through week 145.
Samuel Frank, MD
Teva Pharmaceuticals recently announced findings from the phase 3 open-label, single-arm, 2-cohort, multicenter, ARC-HD extension study (NCT01897896) which demonstrated that treatment with deutetrabenazine (Austedo) was safe, and improved and maintained chorea in patients with Huntington disease (HD) over a 3-year treatment period.1,2
From baseline to week 8, treatment with deutetrabenazine resulted in a mean Total Maximal Chorea (TMC) score decrease of –4.5 points (SD, 3.1; 95% CI, –5.2 to –3.7) for those who completed the double-blind First-HD trial (NCT01795859) (rollover cohort, n = 82) and a decrease of –2.1 points (SD, 3.3; 95% CI, –3.1 to –1.0) for those who converted overnight from a stable tetrabenazine dose (switch arm, n = 37). In both the rollover and switch cohorts, mean motor scores decreased from baseline by –7.1 points (SD, 7.3; 95% CI, –8.8 to –5.5) and –2.4 points (SD, 8.7; 95% CI, –5.4 to 0.5), respectively.
"These data provide important insight into the long-term use of deutetrabenazine for the treatment of chorea associated with Huntington’s disease, which can have a significant functional impact on people’s lives," lead investigator Samuel Frank, MD, associate professor of neurology, and director, HDSA Center of Excellence, Beth Israel Deaconess Medical Center, said in a statement.1 "Results of this study add to the safety and tolerability profile and support deutetrabenazine as a treatment choice for this progressive condition."
Deutetrabenazine, a vesicular monoamine transporter 2 (VMAT2) inhibitor FDA-approved for treatment of tardive dyskinesia and chorea associated with HD, was assessed in a cohort of 119 patients with HD in ARC-HD, with drug dosage that ranged from 6 mg to 72 mg daily. Changes in Unified Huntington’s Disease Rating Scale (UHDRS) total motor score (TMS) and TMC score from baseline to week 8, as well as those from week 8 to week 145, were evaluated as both efficacy and safety end points during the study. For TMS and TMC, lower scores indicated better motor function and less chorea, respectively.
Overall, 81 (68%) patients who received deutetrabenazine treatment completed the long-term follow-up. For those who rolled over from First-HD, retitration was needed, and by week 8, the mean daily dose of the agent was 38.1 mg (SD, 10.53). For the switch cohort, the mean daily dose of deutetrabenazine at that time point was 36.5 mg (SD, 12.9). Across cohorts, the mean daily dose after titration was 37.6 mg (SD, 11.3) at week 8 and 45.7 mg (SD, 16.7) at the final visit.
From week 8 to week 145 (or end of treatment, whichever was earlier), patients on deutetrabenazine showed a minimal change of –0.5 points (SD, 5.2; 95% CI, –1.9 to 1.0) in TMC score but an increase in the TMS score (mean change, 8.2; SD, 11.9; 95% CI, 4.8-11.5). Notably, there were no unexpected adverse events (AEs) upon drug withdrawal, and chorea scores increased by a mean of 4.7 (SD, 4.6) units from week 8 to the 1-week follow-up.
EDG-5506, an orally administered small molecule agent, showed nearly a 40% decrease in levels of serum creatine kinase in a phase 1b trial of adults with Becker muscular dystrophy.
"Chorea is one of the most striking physical manifestations of Huntington’s Disease that occurs in approximately 90% of HD patients," Eran Harary, MD, senior vice president, Global Head of Specialty R&D, Teva, said in a statement.1 "As a disease that can have significant functional impact on patients’ and caregivers’ lives, we’re proud to share these new data to provide valuable insights for this community of patients and for those who provide care to them each day."
Deutetrabenazine showed a safety profile that was similar to previous studies. For those who completed the double-blind study (rollover arm) and those who converted overnight from a stable tetrabenazine dose (switch arm), the exposure-adjusted incidence rates (EAIRs) for AEs were 2.57% and 4.02%, respectively. At week 8, there were no increases in the incidence of any abnormal electrocardiogram parameters relative to baseline in either cohort. There was 1 death in the rollover cohort of sudden cardiac arrest that was deemed unlikely to be related to the study drug. No notably changes in safety assessments were observed over the treatment period.
