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Positive Results Reported From Pivotal Trial of SD-809 for Chorea Associated With Huntington’s Disease
Positive efficacy and safety results have been reported from a pivotal phase III trial of SD-809 (Auspex Pharmaceuticals) for the treatment of chorea in patients with Huntington's disease (HD).
In addition to meeting the study’s primary efficacy endpoint, significant improvements in both patient and clinical global impressions of change and quality of life were observed. The study also demonstrated favorable safety and tolerability profiles for SD-809, including low rates of depression, somnolence, akathisia/restlessness, and anxiety.
SD-809 has the same mechanism of action as the vesicular monoamine transporter 2 (VMAT) inhibitor tetrabenazine (Xenazine, Valeant International/Lundbeck), but it is broken down in the body more slowly than tetrabenazine.
HD is a genetic disorder that causes a variety of symptoms, including involuntary movements and problems with emotion, behavior, thinking, and the processing of information. Approximately 90% of patients with HD develop chorea, which is characterized by involuntary, excessive movements that can affect all parts of the body and interfere with motor functions. As a result, chorea associated with HD can be severely debilitating.
The pivotal First-HD trial was a randomized, double-blind, placebo-controlled, parallel-group study evaluating the efficacy, safety, and tolerability of SD-809 in the management of chorea associated with HD. The trial’s primary efficacy endpoint was the change from baseline to maintenance therapy in the Total Maximal Chorea (TMC) score of the Unified Huntington's Disease Rating Scale (UHDRS). Key secondary endpoints included treatment success (based on the patient’s global impression of change [PGIC] and on the clinical global impression of change [CGIC]), quality of life, and balance.
Ninety patients were randomly assigned to receive either SD-809 or placebo for 12 weeks. The patients were titrated weekly to an optimal dose up to week 8; were on maintenance therapy for 4 weeks, and were taken off study medication in the final week of the study. A total of 87 patients completed the study; one patient in the SD-809 group and two in the placebo group discontinued.
SD-809 met the pre-specified primary efficacy endpoint. Patients taking SD-809 achieved a meaningful improvement of 2.5 points on the TMC score from baseline to maintenance therapy compared with placebo (P < 0.0001).
The clinical relevance of the change in chorea was assessed by four prespecified secondary endpoints. Three of these endpoints, including two patient-rated measures of benefit, demonstrated the statistically significant superiority of SD-809 over placebo. These endpoints were PGIC (P = 0.002 for SD-809 vs. placebo), CGIC (P = 0.002), and SF-36 Physical Functioning Score from baseline to week 12 (P = 0.03).
One patient experienced two serious adverse events (SAEs) (cholecystitis and agitated depression) in the SD-809 group, and one patient experienced one SAE (exacerbation of chronic obstructive pulmonary disease [COPD]) in the placebo group. The same patient experiencing the SAEs in the SD-809 group also reported suicidal ideation, which was not considered an SAE.