Revance Therapeutics announced results for two Phase 2a open-label, dose escalation studies of its investigational drug candidate DaxibotulinumtoxinA for Injection in the treatment of dynamic forehead lines (FHL) following glabellar (frown) line injections and lateral canthal lines (LCL). Both studies demonstrated positive efficacy results and that DaxibotulinumtoxinA for Injection was well tolerated. Additionally, the studies evaluated a range of doses, providing directional guidance on the impact of dose on efficacy and duration of effect.
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 portion 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, 100 percent of 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 both studies, 100 percent of 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.
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. 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.
The U.S. Food and Drug Administration (FDA) has given Revance a Prescription Drug User Fee Act (PDUFA) VI program date of November 25, 2020 for DaxibotulinumtoxinA for Injection as a potential treatment for moderate to severe glabellar lines.
“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,” said Roman Rubio, MD, senior vice president of clinical development at Revance. “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.
Additional information about each Phase 2a study can be found at www.clinicaltrials.gov.