Revance Therapeutics, Inc. (NASDAQ:RVNC), a biotechnology company developing neuromodulators for use in treating aesthetic and therapeutic conditions, today announced initiation of patient dosing in the company’s ASPEN Phase 3 clinical program for its investigational drug candidate DaxibotulinumtoxinA for Injection (RT002) for the treatment of cervical dystonia (CD), a movement disorder of the neck.

"In our Phase 2 study, treatment with RT002 resulted in patients realizing clinically meaningful relief from the pain and disability associated with cervical dystonia for at least 24 weeks," said Roman Rubio, MD, Senior Vice President of Clinical Development at Revance. "Current botulinum toxin injections for cervical dystonia are administered at approximately 12-week intervals. With the potential for twice yearly administration, RT002 could represent a meaningful advancement in treatment, providing significantly prolonged improvement of symptoms in patients."

"The initiation of our pivotal program is an important milestone for Revance as we advance our novel long-lasting neuromodulator RT002 in this important therapeutic indication," said Dan Browne, President and Chief Executive Officer at Revance. "The FDA granted Orphan Drug Designation for the use of RT002 in the treatment of cervical dystonia, and we believe that RT002 can deliver improved patient outcomes not only in cervical dystonia therapy, but in a number of other muscle movement disorders as well."

Positive results from the company’s open-label, dose-escalating Phase 2 clinical study of RT002 injectable in the treatment of cervical dystonia were recently published in Movement Disorders Clinical Practice. The trial demonstrated a median duration of effect of at least 24 weeks for each of the three dose cohorts studied. For reference, current treatment of cervical dystonia calls for injection of botulinum toxin approximately every three months (12 weeks), or four times per year.

The Phase 2 trial achieved its primary efficacy endpoint, demonstrating a clinically significant mean reduction of 38 percent in the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) - Total score from baseline at Week 4 across all three cohorts. This mean reduction continued to increase to 50 percent at Week 6, was 42 percent at Week 12, and was maintained at or above 30 percent through Week 24. For reference, placebo-controlled trials for botulinum toxin type A products approved to treat cervical dystonia had a reduction in the TWSTRS – Total score from baseline of 21 percent to 26 percent at Week 4 and 13 percent to 16 percent at Week 12.

Regarding the Phase 2 study’s key secondary endpoint – percentage of responders showing improvement on Clinician Global Impression of Change (CGIC) – 97 percent of all patients experienced an improvement in cervical dystonia symptoms at Week 4. In all three cohorts, RT002 injectable appeared to be generally safe and well-tolerated through Week 24. There were no serious adverse events and no dose-dependent increase in adverse events. The treatment-related adverse events were generally transient and mild to moderate in severity, with one case of neck pain reported as severe. The most common adverse events were dysphagia, or difficulty in swallowing (14 percent), of which all cases were mild in severity, injection site redness (8 percent), injection site bruising (5 percent), injection site pain (5 percent), muscle tightness (5 percent) and muscle weakness (5 percent).

The global neuromodulator opportunity for muscle movement disorders in 2017 was estimated to be more than $1 billion. The company plans to initiate a Phase 2 program in upper limb spasticity, the largest indication in the muscle movement segment, later this year.

ASPEN Phase 3 Clinical Program in Cervical Dystonia

The company’s ASPEN Phase 3 clinical program consists of two trials to evaluate the safety and efficacy of RT002 injectable for the treatment of cervical dystonia in adults: 1) a randomized, double-blind, placebo-controlled, parallel group trial, and 2) an open-label, long-term safety trial. The program is expected to enroll a total of approximately 300 patients at multiple sites in the United States, Canada, and Europe.

Randomized Trial: Patients will be randomized to either a low dose or high dose of RT002 injectable or placebo treatment. Post-treatment, patients will be followed for a maximum of 36 weeks. The primary efficacy endpoint of the trial will be the change from baseline in the TWSTRS – Total score. Key secondary endpoints include the duration of treatment effect, the Clinical and Patient Global Impression of Changes, and adverse events. Further, the trial features exploratory efficacy assessments, including the Cervical Dystonia Impact Profile (CDIP)-58, a disease-specific, patient-rated questionnaire that measures quality of life.

Open-Label Trial: Patients will receive up to four continuous treatment cycles of RT002 injectable over the 52-week observation period. Primary endpoints of the trial are safety and immunogenicity after multiple cycles of treatment with RT002. Key secondary endpoints are the change from baseline in TWSTRS – Total score, and the duration of treatment effect, as well as overall treatment response based on the Clinical and Patient Global Impression of Change.