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 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 aailable 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.
CONTACT: Corporate Communications Contacts:
For Media:
Dan Budwick, Pure Communications, Inc.
dan@purecommunicationsinc.com
(973) 271-6085
For Investors:
Monique Allaire Lyons, Pure Communications, Inc.
monique@purecommunicationsinc.com
(617) 895-9511