Studies in motion

LA JOLLA, Calif.—Auspex Pharmaceuticals Inc., a biopharmaceutical company dedicated to developing innovative medicines for people with movement disorders and other rare diseases, has had three major announcements involving clinical trials with its compound SD-809. Founded in 2001, the company is focused on substitution of deuterium for hydrogen within known active molecules to create superior drug candidates with altered therapeutic profiles.

In November 2014, SD-809 was granted Orphan Drug designation by the U.S. Food and Drug Administration (FDA) for the treatment of Huntington’s disease. In December, Auspex announced positive top-line efficacy and safety results from its Phase 3 registration trial evaluating SD-809 for the treatment of chorea associated with Huntington’s disease, called First-HD, and its switch study called ARC-HD. First-HD was a 1:1 randomized, double-blind, placebo-controlled, parallel-group trial evaluating the efficacy, safety and tolerability of SD-809. Based on that data, Auspex expects to file a New Drug Application for SD-809 by mid-2015 in this indication. Huntington’s disease, a genetic disorder that causes a wide variety of symptoms including involuntary movements, problems with emotion, behavior, thinking and processing information, ultimately leads to death. Almost all patients with Huntington’s disease develop chorea, characterized by involuntary, excessive movements that can impact all parts of the body, interfere with motor functions and be severely debilitating.

Data from the study showed that patients who switched from the current standard of care, tetrabenazine, to SD-809 maintained chorea control at both week one and week four. According to Dr. Samuel A. Frank, associate professor of neurology at Boston University School of Medicine and principal investigator for First-HD, “For many individuals with Huntington’s disease, chorea is a key symptom impacting safety, function and quality of life. New, safe and tolerable therapies for chorea treatment are clearly needed to make this disease an increasingly treatable condition. The primary and secondary efficacy results from this study were confirmed by the Huntington Study Group independent analysis. These clear and unequivocal results are clinically meaningful and suggest that SD-809 may play an important role in the treatment of Huntington’s disease symptoms.”

According to Dr. Pratik Shah, president and CEO of Auspex, “Patients who received SD-809, our lead drug, showed an improvement in a standardized score measuring involuntary movement, compared with those given a placebo. SD-809 also significantly improved the patients’ quality of life, lowering rates of depression and anxiety. About 90 percent of those suffering from Huntington’s disease develop chorea, characterized by involuntary, excessive movements that can impact all parts of the body and interfere with motor functions.”

Shah says that the company was also running an additional trial to determine whether chorea management remained under control when patients were switched overnight to SD-809 from tetrabenazine. According to the study, the chorea score for the drug improved by a point in the first and fourth weeks. Tetrabenazine, which is marketed as Xenazine in the United States, is expected to lose its market exclusivity for treatment of chorea in August 2015. If approved, SD-809 could compete with generic versions of the drug.

In January, Auspex announced favorable top-line safety results from its thorough QT (TQT) clinical trial evaluating the effects of SD-809 on cardiac repolarization, based on placebo-corrected, time-matched changes from baseline in the corrected QT (QTc) interval. The TQT clinical trial demonstrated that at two different dose levels, SD-809 had no clinically significant effect on cardiac repolarization as assessed by the QT interval. A tetrabenazine arm was included for comparison and demonstrated an increase in QTc that is consistent with the effect reported in the FDA label for Xenazine. The clinical trial’s assay sensitivity was established by the observation of characteristic QTc prolongation following dosing with moxifloxacin.

“We are very pleased with the results of this TQT study,” notes Shah. “This study is another important step forward in our path to advance SD-809 to market and bring this much-needed therapy to patients living with serious movement disorders.”

Also in January, Auspex related that the FDA has granted Orphan Drug designation to the company’s investigational compound SD-809 for the treatment of Tourette syndrome in the pediatric population, defined as zero through 16 years of age. Auspex is currently evaluating the preliminary efficacy, pharmacokinetic and safety profile of SD-809 in a Phase 1b clinical trial for the treatment of tics associated with Tourette syndrome, a hyperkinetic movement disorder manifested by motor and phonic tics, which are often accompanied by neurobehavioral disorders such as attention-deficit hyperactivity disorder and obsessive-compulsive disorder. Top-line data from this trial are expected by mid-2015.

“Receiving Orphan Drug designation of SD-809 for the treatment of Tourette syndrome, in addition to Huntington’s disease, is an important step forward in our goal of bringing this novel treatment approach to the patients and families affected by these serious disorders,” according to Shah. “There have been no new drugs developed for Tourette syndrome in over 30 years. We believe that physicians consider the two approved neuroleptics to be inadequate. These treatments carry, among other adverse events, the risk of causing permanent neurologic deficits, such as tardive dyskinesia. The Orphan Drug designation recognizes the significant need that exists among children living with this debilitating disease, and we look forward to assessing the potential role that SD-809 may have in addressing that.”