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Auspex Announces Positive Topline Results From Registration Trial of SD-809 for Chorea Associated With Huntington's Disease

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| Source: Auspex Pharmaceuticals, Inc.

Pivotal Phase 3 Trial Met Primary and Multiple Key Secondary Efficacy Endpoints; Favorable Safety and Tolerability Demonstrated

ARC-HD Trial Shows Successful Maintenance of Chorea Control After Switch to SD-809

NDA Submission Planned by Mid-2015

Conference Call Scheduled for 4:30 PM ET / 1:30 PM PT Today

LA JOLLA, Calif., Dec. 16, 2014 (GLOBE NEWSWIRE) -- Auspex Pharmaceuticals, Inc. (Nasdaq:ASPX), a biopharmaceutical company dedicated to developing innovative medicines for people with movement disorders and other rare diseases, today announced positive topline efficacy and safety results from its Phase 3 registration trial evaluating SD-809 for the treatment of chorea associated with Huntington's disease (HD), called First-HD. In addition to meeting the primary efficacy endpoint, significant improvements in both patient and clinical global impressions of change and quality of life were observed. Importantly, the study showed a favorable safety and tolerability profile, including low rates of depression, somnolence, akathisia/restlessness and anxiety. In addition, Auspex announced results from an analysis of the completed four-week Switch portion of the ARC-HD study, which also has an ongoing long-term safety component. Data from the study show that patients who switched from the current standard of care, tetrabenazine, to SD-809 maintained chorea control at both week one and week four.

Huntington's disease is a genetic disorder that causes a wide variety of symptoms including involuntary movements, problems with emotion, behavior, thinking, processing information, and ultimately leads to death. Approximately 90 percent of patients with Huntington's disease will develop chorea, which is characterized by involuntary, excessive movements that can impact all parts of the body and interferes with motor functions. As a result, chorea associated with Huntington's disease can be severely debilitating.

"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," said Samuel A. Frank, M.D., associate professor of neurology, Boston University School of Medicine and principal investigator for First-HD. "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."

First-HD Topline Results

First-HD was a 1:1 randomized, double-blind, placebo-controlled, parallel-group trial evaluating the efficacy, safety and tolerability of SD-809 in the management of chorea associated with Huntington's disease. The primary efficacy endpoint for the study was the change from baseline to maintenance therapy in the Total Maximal Chorea (TMC) score of the Unified Huntington's Disease Rating Scale (UHDRS). There were four pre-specified key secondary endpoints that were tested on a hierarchical basis: treatment success based on patient global impression of change (PGIC) and clinical global impression of change (CGIC), quality of life and balance. Other pre-specified motor endpoints were also analyzed. A total of 90 patients (45 in each group) were enrolled for evaluation over 13 weeks: patients were titrated weekly to an optimal dose up to week eight; were on maintenance therapy for four 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 to placebo (p < 0.0001). Additional results from First-HD are as follows:

           
Pre-Specified Motor Endpoints SD-809 Placebo Treatment Effect Favors P-Value
Change in TMC Score1 from
Baseline to Maintenance Therapy*
4.4 Point
Improvement
1.9 Point
Improvement
Improvement of
2.5 Points over Placebo
SD-809 p < 0.0001
Percent Change in TMC Score
from Baseline to Maintenance Therapy
37 Percentage Points
Improvement
16 Percentage
Points Improvement
Improvement of
21 Percentage Points
over Placebo
SD-809 p < 0.0001
Change in Total Motor Score1 (TMS)
from Baseline to Maintenance Therapy
7.4 Point
Improvement
3.4 Point
Improvement
Improvement of
4.0 Points over Placebo
SD-809 p = 0.002
1TMC and TMS are subscales of the Unified Huntington's Disease Rating Scale (UHDRS)
*Primary efficacy endpoint

The clinical relevance of the change in chorea was assessed by four pre-specified secondary endpoints. As summarized in the following table, the first three key secondary endpoints, including two patient-rated measures of benefit, showed statistically significant superiority of SD-809 over placebo.

     
Pre-specified Key Secondary Endpoints2 Favors P-Value
1. Patient Global Impression of Change (PGIC)3 SD-809 p = 0.002
2. Clinical Global Impression of Change (CGIC)3 SD-809 p = 0.002
3. SF-36 Physical Functioning Score (a Quality of Life measure) from Baseline to Week 12 SD-809 p = 0.03
4. Berg Balance Test SD-809 p = 0.14
2 Analyzed using a pre-specified hierarchical testing procedure
3 Success defined as much improved or very much improved

 In general, SD-809 was well tolerated; there was no difference in the rate of dose reduction between SD-809 and placebo (6.7% in each group). Results from First-HD show a favorable safety and tolerability profile of SD-809; following are the number of patients reporting adverse events by system organ class: 

     
System Organ Class SD-809
n = 45
Placebo
n = 45
Psychiatric Disorders 8 (17.8%) 8 (17.8%)
Nervous System Disorders 8 (17.8%) 10 (22.2%)
All Other Body Systems    
Cardiac Disorders 0 (0.0%) 3 (6.7%)
Ear & Labyrinth 1 (2.2%) 1 (2.2%)
Eye Disorders 1 (2.2%) 1 (2.2%)
General Disorders 7 (15.6%) 8 (17.8%)
Gastrointestinal Disorders 9 (20%) 9 (20%)
Hepatobiliary Disorders 1 (2.2%) 0 (0.0%)
Infections and Infestations 5 (11.1%) 5 (11.1%)
Injury, Poisoning and Procedural Complications 4 (8.9%) 6 (13.3%)
Investigations 6 (13.3%) 3 (6.7%)
Musculoskeletal and Connective Tissue Disorders 2 (4.4%) 3 (6.7%)
Renal and Urinary Disorders  2 (4.4%) 1 (2.2%)
Reproductive Systems and Breast Disorders 1 (2.2%) 0 (0.0%)
Respiratory, Thoracic and Mediastinal Disorders 1 (2.2%) 3 (6.7%)
Skin and Subcutaneous Tissue Disorders 2 (4.4%) 1 (2.2%)
Vascular Disorders 2 (4.4%) 0 (0.0%)

The number of patients reporting adverse events in the system organ classes of psychiatric, nervous system, gastrointestinal and other general disorders are listed below:

       
System Organ Class Adverse Event Term SD-809
n = 45
Placebo
n = 45
PSYCHIATRIC Insomnia 3 (6.7%) 2 (4.4%)
DISORDERS Depression/Agitated Depression 2 (4.4%) 3 (6.7%)
  Abnormal Dreams 1 (2.2%) 1 (2.2%)
  Agitation 1 (2.2%) 0 (0.0%)
  Anxiety 1 (2.2%) 1 (2.2%)
  Suicidal Ideation 1 (2.2%) 0 (0.0%)
  Compulsions 0 (0.0%) 1 (2.2%)
  Impulsive Behavior 0 (0.0%) 1 (2.2%)
  Sleep Disorder 0 (0.0%) 3 (6.7%)
NERVOUS Somnolence 5 (11.1%) 2 (4.4%)
SYSTEM Dizziness 2 (4.4%) 4 (8.9%)
DISORDERS Akathisia/Restlessness 1 (2.2%) 1 (2.2%)
  Cognitive Disorder 1 (2.2%) 0 (0.0%)
  Drooling 1 (2.2%) 0 (0.0%)
  Dyskinesia 1 (2.2%) 0 (0.0%)
  Migraine 1 (2.2%) 0 (0.0%)
  Headache 0 (0.0%) 3 (6.7%)
  Loss of Consciousness 0 (0.0%) 1 (2.2%)
  Syncope 0 (0.0%) 1 (2.2%)
GENERAL Irritability 3 (6.7%) 6 (13.3%)
DISORDERS Fatigue 3 (6.7%) 2 (4.4%)
  Gait disturbance 1 (2.2%) 0 (0.0%)
  Chest pain 1 (2.2%) 0 (0.0%)
  Hangover 1 (2.2%) 0 (0.0%)
GASTRO- Diarrhea 4 (8.9%) 0 (0.0%)
INTESTINAL Dry mouth 4 (8.9%) 3 (6.7%)
DISORDERS Constipation 2 (4.4%) 1 (2.2%)
  Nausea 1 (2.2%) 2 (4.4%)
  Abdominal pain upper 1 (2.2%) 0 (0.0%)
  Dyspepsia 1 (2.2%) 0 (0.0%)
  Frequent bowel movements 1 (2.2%) 0 (0.0%)
  Gastrointestinal pain 1 (2.2%) 0 (0.0%)
  Vomiting 0 (0.0%) 3 (6.7%)
  Dysphagia 0 (0.0%) 1 (2.2%)
  Flatulence 0 (0.0%) 1 (2.2%)
  Salivary hypersecretion 0 (0.0%) 1 (2.2%)

There was one patient with two serious adverse events (cholecystitis and agitated depression) in the SD-809 group, and one patient with one serious adverse event (exacerbation of COPD) in the placebo group. The same patient experiencing the serious adverse events in the SD-809 group also reported suicidal ideation, which was not considered a serious adverse event.

"The data from both the First-HD and ARC-HD studies suggest clear efficacy and an excellent safety and tolerability profile for SD-809," said Joseph Jankovic, MD, professor of neurology, Distinguished Chair in Movement Disorders and director, Parkinson's Disease Center and Movement Disorders Clinic, Baylor College of Medicine and a treating investigator in the studies. "The results are very exciting and represent terrific news for patients living with Huntington's disease and for the physicians who treat them. Any drug that suppresses chorea associated with Huntington's disease, with such a low rate of somnolence and depression, as suggested by these findings, would be a welcome addition to the treatment options available for my patients. I am especially grateful to my patients who volunteered to participate in these studies." 

More than 90 percent of patients who completed First-HD enrolled into Auspex's long-term safety study of SD-809. Complete results of the First-HD study will be reported in 2015.

ARC-HD Switch Study

In parallel to First-HD, Auspex completed the four-week Switch portion of the ARC-HD study, which has an ongoing long-term safety component. Although designed primarily as a safety study, maintenance of chorea control was assessed after switching patients overnight from tetrabenazine to SD-809 (at approximately half the dose of tetrabenazine).

All available data through eight weeks following the switch were included in the analysis. After switching from tetrabenazine to SD-809, chorea was assessed at one and four weeks. Dose adjustments were permitted after week one. The mean total chorea score decreased by approximately one point from baseline on the TMC score.

  • Week one change for 36 patients was -0.8 ± 0.4 (mean ± standard error)
  • Week four change for 35 patients was -0.8 ± 0.5

In addition, there were 21 patients for whom data were available at week eight; these data demonstrated an improvement of 1.9 (± 0.8) points on the TMC score. Data for the remaining 15 patients will be available at a future date.

The safety and tolerability experience observed in ARC-HD Switch over the four-week period was consistent with the experience observed in First-HD. The most commonly reported adverse events in ARC-HD Switch patients were somnolence, fall, and nasopharyngitis.

"The strong efficacy and safety results seen in both the First-HD and ARC-HD Switch studies confirm our belief in SD-809 as a highly promising new medicine for the treatment of chorea associated with Huntington's disease," said Pratik Shah, Ph.D., president and chief executive officer at Auspex Pharmaceuticals. "Patients with chorea associated with Huntington's disease have been waiting for too long for a new therapeutic option. We are committed to rapidly advancing SD-809 along its regulatory pathway and submitting an NDA by mid-2015. In addition, we remain fully committed to exploring the therapeutic promise of SD-809 in other movement disorders, including tardive dyskinesia and Tourette syndrome."

Upcoming SD-809 Clinical Data and Other Milestones

SD-809 continues to be evaluated in other clinical studies. Auspex anticipates reporting the following data from various studies in 2015:

  • Thorough QT study in the first quarter of 2015;
  • ARM-TD pivotal study for the treatment of tardive dyskinesia in mid-2015, and;
  • Phase 1b study in Tourette syndrome in mid-2015.

Based on the data reported today, Auspex expects to file a New Drug Application (NDA) for SD-809 for the treatment of chorea associated with Huntington's disease by mid-2015.

Auspex also expects to report Phase 1 data for SD-560, a deuterated form of pirfenidone, by mid-2015.

Conference Call Today

Auspex will host a conference call and live audio webcast with slides today at 4:30 PM ET, 1:30 PM PT. To participate in the conference call, please dial 1-844-834-1429 (domestic) or 1-484-653-6711 (international) and refer to conference ID 54690193. A live webcast and slides can be accessed under "Events & Presentations" in the Investor Relations section of the company's website at www.auspexpharma.com. The archived webcast will be available on the company's website beginning approximately two hours after the event.

About the First-HD Trial

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. The 12-week trial was designed to evaluate and generate label information for the safety, tolerability and efficacy of SD-809 for treating chorea associated with Huntington's disease. The primary endpoint was a change in Total Maximum Chorea (TMC), a standardized score from baseline to maintenance therapy defined as the average of values from Week 9 and Week 12 visits. Patients were treated with SD-809 or placebo starting at 6 mg once per day to up to 24 mg twice per day (48 mg total maximum daily dose). This study was conducted at centers in the United States and Canada, in collaboration with the Huntington Study Group.

About the ARC-HD Switch Trial

ARC-HD Switch is an open-label clinical trial in 37 patients with chorea associated with Huntington's disease in which safety, tolerability and chorea control are assessed in patients switching from stable doses of tetrabenazine to SD-809, which is administered in lower doses and with a simplified dosing regimen. At the time of this analysis, data were available from 36 patients at week one, 35 patients at week four and 21 at week eight. The study was designed to provide guidance to physicians on how to switch patients' treatment from tetrabenazine to SD-809. The analysis was not designed to compare the safety and tolerability of SD-809 to tetrabenazine. Participating patients are eligible to receive open-label SD-809 treatment in a one-year long-term safety study. The study is being conducted at centers in the United States, Canada and Australia.   

About Huntington's Disease

Huntington's disease is a genetic disorder that causes certain cells in the brain to die over time. This causes a wide variety of symptoms including involuntary movements, problems with emotion and behavior, and problems with thinking and processing information. Depression and suicide is common within this patient population, with a lifetime prevalence of depression of around 40 percent; more than 25 percent of patients attempt suicide at some point in their lives. More than 30,000 people in the US and Canada are symptomatic for Huntington's disease and many more are genetically at risk of developing it.

The most visually prominent symptom of Huntington's disease is chorea, which can appear as involuntary, excess movements that can impair a patient's quality of life and be incredibly debilitating. At first, the movements may be subtle and be mistaken as twitching, but may develop into more pronounced movements over time. Approximately 90 percent of people with Huntington's disease will experience chorea at some point. Currently, there is only one FDA approved treatment for a symptom of Huntington's disease, giving physicians limited approved options to care for these patients.

About the Huntington Study Group (HSG)

HSG is an independent not-for-profit network of more than 400 clinical investigators, coordinators and scientists from 100 participating universities and clinics in the United States, Canada, Europe, Australia, New Zealand and South America who provide comprehensive care for Huntington disease (HD) patients and families and carry out multi-center clinical research including observational studies and controlled clinical trials. The mission of the HSG is to seek treatments that make a difference to those affected by HD.

About Auspex Pharmaceuticals

Auspex Pharmaceuticals is a biopharmaceutical company dedicated to developing innovative medicines for hyperkinetic movement disorders and other rare diseases. Auspex employs its proprietary technology to create patent-protected, new chemical entities from known, clinically proven pharmacologics. The company's lead product SD-809 is in final stages of development for the treatment of chorea associated with Huntington's disease, a neurodegenerative movement disorder that impacts cognition, behavior and movements. In addition, Auspex is investing in the broad potential of SD-809 for the treatment of other movement disorders, including tardive dyskinesia and tics associated with Tourette syndrome. The company's pipeline also includes SD-560, being developed for fibrotic conditions. For further information, please visit the company's website www.auspexpharma.com.

Forward-Looking Statements

Statements made in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, statements regarding Auspex's ability to successfully complete its ongoing clinical trials and development programs, Auspex's ability to obtain regulatory approval for its product candidates and market penetration and acceptance of its product candidates. Risks that contribute to the uncertain nature of the forward-looking statements include: Auspex's future preclinical studies and clinical trials may not be successful; changes in regulatory requirements in the United States and foreign countries may prevent or significantly delay regulatory approval of Auspex's product candidates; Auspex may change its plans to develop and commercialize its product candidates; the U.S. Food and Drug Administration (FDA) may not agree with Auspex's interpretation of the data from clinical trials of its product candidates; Auspex may decide, or the FDA may require Auspex, to conduct additional clinical trials or to modify Auspex's ongoing clinical trials; Auspex may experience delays in the commencement, enrollment, completion or analysis of clinical testing for its product candidates, or significant issues regarding the adequacy of its clinical trial designs or the execution of its clinical trials, which could result in increased costs and delays, or limit Auspex's ability to obtain regulatory approval; the third parties with whom Auspex has partnered with for the development of its product candidates and upon whom Auspex relies to conduct its clinical trials and manufacture its product candidates may not perform as expected; Auspex's product candidates may not receive regulatory approval or be successfully commercialized; unexpected adverse side effects or inadequate therapeutic efficacy of Auspex's product candidates could delay or prevent regulatory approval or commercialization; Auspex may be unable to obtain and maintain intellectual property protection for its product candidates; the loss of key scientific or management personnel; Auspex's ability to obtain additional financing; and the accuracy of Auspex's estimates regarding expenses, future revenues and capital requirements. All forward-looking statements contained in this press release speak only as of the date on which they were made. Other risks and uncertainties affecting Auspex are described more fully in Auspex's filings with the Securities and Exchange Commission. Auspex undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.

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