First-HD Results Released
Auspex announces promising results from First-HD trial of deuterated tetrabenazine (SD-809)
By: Meredith A. Achey, BM
On December 16, 2014, Auspex Pharmaceuticals announced positive top-line results for the “First Time Use of SD-809 in Huntington Disease” (First-HD) registration trial of SD-809, a deuterated formulation of tetrabenazine (see HD Insights, Vol. 7). The company also released preliminary results of the ongoing open-label “Alternatives for Reducing Chorea in HD” (ARC-HD) study showing that individuals who switched from tetrabenazine to SD-809 maintained chorea control while taking SD-809 (see Table 1 for a summary of the trials). The complete press release is available here.
The primary efficacy endpoint for First-HD was improvement in the total maximal chorea score of the Unified Huntington’s Disease Rating Scale. Trial participants who took SD-809 showed an average improvement of 2.5 points (p<0.0001) from baseline to maintenance therapy. In addition, secondary endpoints assessing clinical relevance, including patient global impression of change, clinical global impression of change, and change in the SF-36 physical functioning score (a quality of life measure) showed improvement over placebo (p<0.05), while the Berg Balance test did not show significant improvement (p=0.14). More than 90% of First-HD participants enrolled in the open-label, long-term follow-up ARC-HD study.
ARC-HD “Switch” was completed in parallel to First-HD, as patients currently taking tetrabenazine for chorea control were switched overnight to SD-809 at approximately half their usual dose of tetrabenazine (see Table 1). After four weeks, the 35 individuals for whom data was available showed an average improvement of 0.8 points (standard error 0.5) in total maximal chorea score. After eight weeks, data for 21 individuals showed an average improvement of 1.9 points (standard error 0.8). The safety profile was similar to that in the First-HD study.
These preliminary results have given the HD community hope for improvement in the treatment of HD. Dr. Samuel A. Frank, principal investigator for First-HD, told HD Insights, “Combined with the excellent adverse event profile seen with the analysis to date, we are far in the process of developing another potential treatment option for patients with HD.”
Dr. Francis Walker, Professor of Neurology at Wake Forest University School of Medicine and unaffiliated with the study, told HD Insights, “SD-809 may have advantages over tetrabenazine in that it is taken twice instead of four times daily and seems to have a positive effect on function…by preliminary findings, [SD-809] seems to improve upon an existing treatment for HD related chorea.” He cautioned, however, that, “Yet to be reported is the effect of SD-809 on cognition, an area where tetrabenazine has a mild negative effect.” Dr. Frank highlighted several novel elements of the trial’s design, saying, “This trial… [had] many novel aspects that we may be able [to] apply to other HD trials including capacity assessment in the context of a clinical trial, easy swallowing assessment and direct shipping of study drug to participants… [Additionally], we demonstrated that deuterated compounds penetrate the blood brain barrier, a concept that may be applied to other deuterated compounds used for other neurological conditions.”
Full results of First-HD are expected in 2015, and Arc-HD is scheduled to conclude in mid-2015. Auspex CEO Dr. Pratik Shah indicated that the company will submit a New Drug Application to the FDA by mid-2015 for SD-809 as a treatment for chorea in HD. Auspex continues to evaluate SD-809 in other conditions, including tardive dyskinesia and Tourette syndrome.
Auspex announces positive topline results from registration trial of SD-809 for chorea associated with Huntington’s disease. [Internet]. Auspex Pharmaceuticals; [updated 2014 Dec 31; cited Dec 31 2014]. Available from: investor.auspexpharma.com/releasedetail.cfm?releaseid=887958.