Revance Announces Positive 24-Week Duration of Effect in Interim Results from Phase 2 Cervical Dystonia Trial
December 12, 2016
- RT002 injectable appeared to be generally safe and well-tolerated -
- RT002 injectable displayed clinically significant impact on cervical dystonia signs and symptoms -
- Revance to host conference call at
The trial enrolled 37 subjects and follows three sequential treatment cohorts for up to a total of 24 weeks after treatment for each cohort. The trial's first cohort of 12 subjects received a single dose of up to 200 units of RT002 injectable, the second cohort of 12 subjects received between 200 and 300 units, and the third cohort received from 300 to 450 units. Later-enrolled subjects in the second and third cohorts have yet to complete the trial's 24-week protocol. Today's results are therefore preliminary, with final results expected in the first half of 2017.
Interim Results from the Phase 2 Cervical Dystonia trial:
- SAFETY: In all three cohorts, RT002 injectable appeared to be generally safe and well-tolerated. There were no serious adverse events and no dose-dependent increase in adverse events. The treatment-related adverse events were transient and mild to moderate in severity, except for one case of neck pain reported as severe, with a duration of 2 days. The most common adverse events were dysphagia, or difficulty in swallowing (10.8%), injection site redness (8.1%), injection site pain (5.4%), muscle tightness (5.4%) and muscle weakness (5.4%). For reference, trials for botulinum type A products approved to treat cervical dystonia have adverse events for dysphagia ranging from 13% to 39%.
- EFFICACY: The trial's 4-week primary efficacy measurement was the improvement in dystonia symptoms as determined by reduction from baseline on the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)-Total score. RT002 injectable showed a clinically significant mean reduction of 16.9 from baseline, or 38%, across all three cohorts. In cohort one, with a mean dose of 174 units, the majority of the 44% reduction observed in the TWSTRS-Total score at Week 4 was preserved at Week 24, with a 33% mean reduction from baseline observed. Clinically meaningful mean reductions in the TWSTRS Severity, Disability and Pain subscales were consistent and observed at all follow-up visits in the first cohort. Later-enrolled subjects in the second and third cohorts have not yet reached the 24-week point. For reference, placebo-controlled trials with botulinum type A products approved to treat cervical dystonia had a reduction in the TWSTRS-Total score from baseline of 14% to 26% at Week 4.
- DURATION OF EFFECT: Duration of effect for this trial was defined as the number of weeks from treatment until the return of symptoms that warrant retreatment, based on the subject's target TWSTRS score. The median duration of effect was at least 24 weeks for subjects in cohort one (n=12), and at least 16 weeks for subjects in cohort two (n=11), using the complete 16 week follow up data. In cohort one, no subjects had returned to baseline at Week 24 and only one subject in cohort two, to date, has returned to baseline, which occurred at the Week 24 visit. In cohort one, RT002 achieved a median duration of at least 24 weeks based on three different assessments, including 1) the number of weeks from treatment until a subject reaches or exceeds their target TWSTRS-Total score, 2) improvement (score > 0) on the Clinician Global Impression of Change (CGIC), and 3) TWSTRS-Total score return to baseline. For reference, current treatment of cervical dystonia calls for injection of botulinum toxin approximately every 3 months, or 4 times per year.
"Patients with cervical dystonia suffer from painful, embarrassing
twisting movements of the neck, often impairing their ability to work,
drive and perform activities of daily living," said lead trial
investigator Dr.
"Cervical dystonia is an ideal therapeutic indication for testing the
attributes of RT002 injectable," said
"Further, RT002 injectable, even at high doses, may deliver a strong safety profile possibly by limiting the spread of toxin, which could avoid life-altering adverse events such as general muscle weakness and difficulty swallowing," Browne continued. "We plan to share the final safety, efficacy, and duration results in 2017 once all cohorts have completed the 24-week assessment period. We then intend to seek regulatory advice from US and EU health authorities to determine the next steps in this clinical program."
The abstract for this Phase 2 clinical trial of RT002 injectable to
treat cervical dystonia was submitted to the Toxins 2017 (
Phase 2 Study Design
Revance's Phase 2 trial is an open-label, sequential, dose-escalating
study to evaluate the safety, preliminary efficacy and duration of
effect of a single treatment of DaxibotulinumtoxinA Injectable (RT002)
for isolated cervical dystonia. Thirty-seven subjects with at least
moderate cervical dystonia were enrolled at multiple sites in
The primary efficacy endpoint of the Phase 2 study is an improvement in dystonia symptoms as measured by change (reduction) from baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total score at four weeks. TWSTRS is a composite scale that covers different features of the cervical dystonia condition. The first part of the scale is based on the physical findings and severity of dystonia, the second part rates the patient's perceived level of disability, and the third part rates the pain. The study protocols also feature a number of secondary efficacy endpoints, including duration of effect and patient-rated quality of life as measured by change from baseline in Cervical Dystonia Impact Profile (CDIP).
All subjects are followed out to nine weeks, after treatment. Subjects with sustained improvement after this initial period of nine weeks continue to be assessed for duration of efficacy and other measures until they return to baseline or for up to a total of 24 weeks after treatment.
Conference Call
Revance management will host a conference call and webcast today at
A replay of the call will be available beginning
About Cervical Dystonia
According to the
Treatments for cervical dystonia include oral medications, botulinum
toxin injections, surgery, and complementary therapies. Botulinum toxin
can help block the communication between the nerve and the muscle and
may alleviate abnormal movements and postures. Current botulinum toxin
treatments for cervical dystonia have a duration of effect of
approximately three months. Cervical dystonia can occur at any age,
although most individuals first experience symptoms in middle age. It
affects several hundred thousand adults and children in
About
Revance, a Silicon Valley-based biotechnology company, is committed to the advancement of remarkable science. The company is developing a portfolio of products for aesthetic medicine and underserved therapeutic specialties, including dermatology, orthopedics and neurology. Revance's science is based upon a proprietary TransMTS® peptide technology, which when combined with active drug molecules, may help address current unmet needs.
Revance's initial focus is on developing daxibotulinumtoxinA, the company's highly purified botulinum toxin, for a broad spectrum of aesthetic and therapeutic indications, including facial wrinkles and muscle movement disorders. The company's lead drug candidate, DaxibotulinumtoxinA for Injection (RT002), is currently in development for the treatment of glabellar lines, cervical dystonia and plantar fasciitis with the potential to be the first long-acting neurotoxin. The company holds worldwide rights for all indications of RT002 injectable and RT001 topical and the pharmaceutical uses of the TransMTS technology platform. More information on Revance may be found at www.revance.com.
"Revance Therapeutics," TransMTS®, "Remarkable Science Changes Everything," and the Revance logo are registered trademarks of Revance Therapeutics, Inc.
Forward Looking Statements
This press release contains forward-looking statements, including statements related to the process and timing of, and ability to complete, current and anticipated future clinical development of our investigational drug product candidates, including but not limited to initiation and design of clinical studies for current and future indications, related results and reporting of such results; statements about our business strategy, timeline and other goals and market for our anticipated products, plans and prospects; and statements about our ability to obtain regulatory approval; and potential benefits of our drug product candidates and our technologies.
Forward-looking statements are subject to risks and uncertainties
that could cause actual results to differ materially from our
expectations. These risks and uncertainties include, but are not limited
to: the outcome, cost, and timing of our product development activities
and clinical trials; the uncertain clinical development process,
including the risks that interim results are not indicative of final
results and that clinical trials may not have an effective design or
generate positive results; our ability to obtain and maintain regulatory
approval of our drug product candidates; our ability to obtain funding
for our operations; our plans to research, develop, and commercialize
our drug product candidates; our ability to achieve market acceptance of
our drug product candidates; unanticipated costs or delays in research,
development, and commercialization efforts; the applicability of
clinical study results to actual outcomes; the size and growth potential
of the markets for our drug product candidates; our ability to
successfully commercialize our drug product candidates and the timing of
commercialization activities; the rate and degree of market acceptance
of our drug product candidates; our ability to develop sales and
marketing capabilities; the accuracy of our estimates regarding
expenses, future revenues, capital requirements and needs for financing;
our ability to continue obtaining and maintaining intellectual property
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information regarding factors that may cause actual results to differ
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