Long-acting neuromodulator daxibotulinumtoxinA for Injection (RT002) delivered positive top-line results in alleviating moderate to severe glabellar lines in the SAKURA 3 Phase 3 open-label, long-term safety study. Completion of this study paves the way for Revance Therapeutics, Inc. to submit a Biologics License Application (BLA) with the FDA, which is on-track for the first half of 2019.

“The results of this trial are exceptional since they demonstrate that RT002 has consistently and predictably produced long duration and high response rates and was well tolerated over successive treatments,” says SAKURA investigator Jean D. Carruthers, MD, who has served as an investigator for multiple FDA-approved neuromodulators, and is a clinical professor at the University of British Columbia. “My study patients were thrilled with their appearance and the longevity RT002 delivered, and they can’t wait for this treatment option. I look forward to the possibility of providing my patients a new, unique neuromodulator that needs just two or fewer treatments a year.”

As a component of the largest clinical program of an aesthetic neuromodulator, the SAKURA 3 study included nearly 2,700 patients and more than 3,800 treatments. Patients received up to three treatments of RT002 and were followed for over a year and a half. Overall, the safety findings were consistent with the known safety profiles for currently available neuromodulators in aesthetics. The rate of treatment-related adverse events decreased over successive treatments. For efficacy, based on investigator assessment, more than 95 percent of patients achieved a score of none or mild glabellar lines at maximum frown at Week 4 after each of three treatments. Measuring duration of effect, the median time to return to baseline glabellar line severity was 28 weeks. The median time to loss of none or mild wrinkle severity was 24 weeks. The SAKURA 3 results were consistent with those in the Phase 3 pivotal trials, SAKURA 1 and SAKURA 2.

Dan Browne, co-founder, president and chief executive officer of Revance said, “We are very excited by these compelling new data, which support RT002 as a next-generation neuromodulator with highly differentiated characteristics. We look forward to working closely with the FDA to bring this important treatment to patients as soon as possible. The success of the SAKURA aesthetic trials, combined with our ongoing therapeutic studies in multiple neuroscience indications, drive our mission to become the leading innovator in neuromodulators.”

Following these results, Revance says it will begin studies in 2019 in forehead and lateral canthal lines (crow’s feet) to explore the use and dosage of RT002 in the upper face.

“The long-term results in these studies, which are consistent and predictable across age groups and prior toxin experience, are extremely impressive,” said SAKURA investigator Steven Fagien, MD, FACS, Aesthetic Eyelid Plastic Surgery, Boca Raton, FL, and one of the world’s foremost experts in injectable neuromodulators. “The SAKURA data demonstrate RT002 provides a trifecta of results – a reassuring safety profile, high patient response rates, and long-lasting results. RT002 has the potential to raise the bar of expectations for neuromodulators in the injectable facial aesthetic landscape.”

Global sales of neuromodulators totaled $4 billion in 2017 and are estimated to nearly double by 2025. Despite this, market penetration has remained below 10 percent for decades, at least in part because currently available short-acting neuromodulators do not address the number one desire of patients and physicians for longer-lasting results.

According to findings from a proprietary landmark survey of more than 2,000 women aged 25-70 conducted on behalf of Revance by The Harris Poll, facial lines and wrinkles are the most concerning visible sign of aging among women in this age range. Still, only seven percent of women said they have used a neuromodulator in the past five years. In addition, the survey also included 246 dermatologists and plastic surgeons who see at least 15 patients a week who receive neuromodulator treatments. Among this group of physicians, 86 percent wish there was a neuromodulator that offered longer-lasting results than what is currently available.

Revance also announced that it has entered into a license agreement with Shanghai Fosun Pharmaceutical Industrial Development Co., Ltd., a wholly-owned subsidiary of Shanghai Fosun Pharmaceutical Co., Ltd, providing Fosun Pharma Industrial with the exclusive rights to develop and commercialize RT002 in mainland China, Hong Kong and Macau.

Under the terms of the agreement, Revance will receive an upfront payment of $30 million within 30 business days of entering into the license agreement and is eligible to receive additional potential development and sales milestone payments of up to $230.5 million, as well as tiered low-double-digit to high-teen royalty payments on future net sales. Fosun Pharma Industrial will be responsible for conducting necessary clinical studies, marketing and sales in the Territory, while Revance will be responsible for manufacturing drug substance and finished drug product for both the clinical and commercial activities in the Territory. There will be no transfer of intellectual property.