Ongoing Clinical Development of SD-809
Phase 3 placebo-controlled registration trial
We have completed a Phase 3 registration clinical trial of SD-809, which we refer to as First-HD. First-HD is a randomized, double-blind, placebo-controlled, parallel-group trial of SD-809 in 90 patients with chorea associated with Huntington’s disease and is designed to evaluate, and generate label information for, the safety, tolerability and efficacy of SD-809 for treating chorea associated with Huntington’s disease. Patients were randomized 1:1 to receive SD-809 once or twice daily or placebo. They were individually titrated to their optimal dosage of study drug during the course of the trial, followed by maintenance therapy at that dose. The overall treatment period was 12 weeks in duration with a titration period that lasted eight weeks and a maintenance period that lasted four weeks. The primary endpoint for this trial was change in TMC score from baseline to maintenance therapy, where final score was defined as the average of values from Week 9 and Week 12 visits. This is the same endpoint that was accepted by the FDA when it considered and approved the NDA for tetrabenazine in 2008. Patients from First-HD were also eligible to enroll in ARC-HD Rollover, a long-term safety clinical trial described below.
Open-label switch and long-term safety clinical trial
In parallel with First-HD, we undertook an additional clinical trial of SD-809, which we refer to as ARC- HD. One component of ARC-HD, referred to as ARC-HD Switch, was a four-week, open-label “switch” trial in 36 patients with chorea associated with Huntington’s disease adequately controlled with tetrabenazine. The objectives of ARC-HD Switch were to evaluate the safety of switching subjects from tetrabenazine to SD-809 and to provide guidance to physicians on how to switch such patients to SD-809. The primary endpoints of ARC-HD Switch are the incidence of adverse events, the duration of time to achieve stable dosing and changes in observed TMC values for patients when treated with tetrabenazine (baseline) as compared to treatment with SD-809.
We have rolled over patients from First-HD and ARC-HD Switch into a 52-week open-label, long-term, safety clinical trial, which is the second component of ARC-HD, referred to as ARC-HD Rollover. In ARC-HD Rollover, subjects will return to the clinic at scheduled intervals for evaluation of safety and chorea control. Further adjustments of SD-809 dosing will be made, if necessary, but not more than weekly, and in 6 mg daily increments.
Planned Clinical Development of SD-809 in Additional Indications
Phase 3 clinical trials for treatment of tardive dyskinesia
We have initiated two safety and efficacy clinical trials of SD-809 for the potential treatment of tardive dyskinesia. ARM-TD (Aim to Reduce Movements in Tardive Dyskinesia) is a Phase 2/3 randomized, double-blind, placebo-controlled, dose-titration clinical trial of SD-809 in approximately 90 patients with tardive dyskinesia. Topline results from this trial are expected in mid-2015. Based on feedback we obtained at a meeting with the FDA, the ARM-TD trial may qualify as one of the two pivotal trials needed for a 505(b)(2) New Drug Application, or NDA, filing, subject to FDA review. The AIM-TD (Addressing Involuntary Movements in Tardive Dyskinesia) clinical trial is a double-blind, placebo-controlled, parallel group trial in approximately 200 people with tardive dyskinesia. We expect topline results from this trial in 2016. Contingent upon successful completion of both studies, we plan to file an NDA for SD-809 for the treatment of tardive dyskinesia in 2016.
Phase 1b clinical trial in Tourette syndrome
We have initiated an open-label preliminary efficacy, pharmacokinetic and safety Phase 1b clinical trial of SD-809 for the treatment of tics associated with Tourette syndrome. We plan to enroll approximately 20 subjects to evaluate preliminary efficacy and safety, in addition to studying the pharmacokinetics of SD-809 in adolescents. We expect topline data from this trial by mid-2015.