Revance Therapeutics, Inc.’s next-generation neuromodulator product, DaxibotulinumtoxinA, safely and effectively smoothed forehead lines and Crow’s feet with a median duration of 27 weeks in forehead lines and 24 weeks in crow’s feet achieved in at least one treatment group, according to two Phase 2a open-label, dose-escalation studies.
DaxibotulinumtoxinA for Injection has been given a Prescription Drug User Fee Act (PDUFA) VI program date of November 25, 2020, by the U.S. Food and Drug Administration.
In the forehead lines study, a total of 61 subjects were randomized into one of four dose groups with each receiving 40 units of DaxibotulinumtoxinA for Injection in the glabellar complex, followed two weeks later by injections of either 12, 16, 24, or 30 units in the forehead for a total study duration of up to 38 weeks. In the crow’s feet study, a total of 63 patients were randomized into one of four dose groups to receive either 12, 24, 36 or 48 units of DaxibotulinumtoxinA for Injection, then followed for up to 36 weeks.
The primary endpoint for efficacy was the percentage of subjects achieving a score of none or mild in wrinkle or line severity at Week 4 either at maximum eyebrow elevation for forehead lines or at maximum smile for crow’s feet. The scores were based on the investigator assessment. In the forehead lines study, all subjects achieved a score of none or mild at Week 4 in at least one treatment group. In the crow’s feet study, 88 percent of subjects achieved a score of none or mild at Week 4 in at least one treatment group.
In addition, the proportion of subjects with a measurable treatment effect, as assessed by the investigator, was analyzed. A dose-dependent change in percent of subjects with at least a one-point change from baseline was observed. In both studies, all subjects achieved a score of at least a one-point change from baseline at Week 4 in at least one treatment group.
One of the exploratory endpoints in these studies was duration of effect, defined as the median time to return to baseline wrinkle severity based on both investigator and patient assessment. At least one dose in each study demonstrated a median duration of effect of 27 weeks in the forehead lines study and 24 weeks in the crow’s feet study.
In these two Phase 2a studies, DaxibotulinumtoxinA for Injection was well-tolerated at all dose levels. Adverse events were mild, localized and transient as expected and there were no treatment-related serious adverse events, as is common with other approved neuromodulators in the treatment of facial lines. The most common treatment-emergent adverse events after forehead line treatment were edema (10 percent), erythema (6.7 percent) and headache (5 percent). There was as single occurrence of mild eyelid ptosis that was fully resolved by Day 9. The most common treatment-emergent adverse events after crow’s feet treatment were nasopharyngitis (11.1 percent), bruising (7.9 percent) and headache (7.9 percent). There were no events of ptosis.
Interim Week 4 data from these two Phase 2a studies were used in the final design of Revance’s current upper facial lines Phase 2 study (glabellar lines, forehead lines and lateral canthal lines), to optimize dosing and injection patterns. Revance is scheduled to report results from that study in the fourth quarter of 2020. “We are very pleased with the results of these two studies, designed to evaluate safety and efficacy, as well as identify safe and effective doses, for DaxibotulinumtoxinA for Injection in the treatment of forehead lines and crow’s feet,” says Roman Rubio, M.D., Senior Vice President of Clinical Development at Revance, in a news release. “The finding that at least one dose in each study produced a response rate of 24-weeks duration provides a compelling initial demonstration that DaxibotulinumtoxinA for Injection holds promise for the treatment of forehead lines and crow’s feet.”
Adds Mark Foley, President and Chief Executive Officer, “Exploring DaxibotulinumtoxinA for Injection in other areas of the upper face beyond glabellar lines provides an expanded body of knowledge on the performance of our long-acting, next-generation neuromodulator. These results are consistent with those observed in our SAKURA Phase 3 program for DaxibotulinumtoxinA for Injection in the treatment of glabellar lines. Our aim is to provide physicians and patients with a true advancement in the treatment of not only facial wrinkles, but also a number of debilitating muscle movement and pain disorders, which are being addressed through ongoing therapeutic clinical trials.”