DaxibotulinumtoxinA for Injection for the Treatment of Glabellar Lines: Results from Each of Two Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Studies (SAKURA 1 and SAKURA 2)

Abstract

Background: DaxibotulinumtoxinA for Injection (DAXI) is a novel botulinum toxin type A formulation in clinical development. A phase 2 dose-ranging study identified an optimal dose and demonstrated efficacy with a median duration of 24 weeks. Methods: In two phase 3, multicenter, randomized, double-blind, placebo-controlled studies (SAKURA 1 and SAKURA 2), subjects with moderate or severe glabellar lines at maximum frown were assigned randomly to receive placebo or 40 U of DAXI. Glabellar lines were evaluated at least every 4 weeks for at least 24 weeks until severity returned to baseline (≤36 weeks). Results: Overall, 609 subjects were enrolled (DAXI, n = 405; placebo, n = 204). DAXI was significantly more effective than placebo in achieving the primary efficacy outcome (≥2-point improvement in glabellar line severity at maximum frown at week 4 according to both investigator and subject ratings): 73.6 percent versus 0.0 percent (SAKURA 1), and 74.0 percent versus 1.0 percent (SAKURA 2) (both p < 0.0001). Composite investigator and subject ratings of maximum frown after DAXI treatment showed that glabellar line severity of none or mild was maintained for a median of 24.0 weeks (SAKURA 1) and 23.9 weeks (SAKURA 2), and glabellar line severity did not return to baseline levels for a median of 27.7 and 26.0 weeks, respectively. DAXI was generally well tolerated, with the most common adverse events related to DAXI treatment being headache (SAKURA 1, 7.0 percent; SAKURA 2, 5.9 percent) and injection-site pain (5.0 percent and 2.4 percent, respectively). Conclusions: Results from both studies were highly consistent. DAXI may offer a prolonged duration of response (median, ≥24 weeks) and is generally well tolerated. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, I.

DaxibotulinumtoxinA for Injection for the Treatment of Glabellar Lines: Efficacy Results From SAKURA 3, a Large, Open-Label, Phase 3 Safety Study

“…Study participants were either rollover subjects who had completed the SAKURA 1 or 2 Phase 3 studies 2 or newly enrolled (de novo) subjects. Eligible subjects included those aged 18 years or older, in good health, with moderate or severe glabellar lines based on the Investigator Global Assessment–Frown Wrinkle Severity (IGA-FWS) and Patient FWS (PFWS) scales.…”

“…The high level of efficacy seen with DAXI in the Phase 2 glabellar lines study was confirmed with consistent results demonstrated in the SAKURA 1 and 2 trials involving a combined total of 609 subjects (405 subjects received a single treatment of DAXI 40U and 204 subjects received placebo). 2 The primary efficacy end point was achieved in both the SAKURA 1 and 2 trials, and the median duration of none or mild glabellar line severity was 24.0 weeks. In the Phase 2, dose-ranging and both Phase 3 SAKURA trials, the adverse event (AE) profile was similar to that seen with other neuromodulators, and no new safety signals were identified.…”

“…The safety and efficacy of a single administration of DAXI 40U for the treatment of moderate or severe glabellar lines was studied in 2 identically designed, pivotal, multicenter, randomized, placebo-controlled, Phase 3 trials (SAKURA 1 and SAKURA 2). 2 The DAXI dose was determined based on a Phase 2, dose-ranging clinical trial in which the 40U dose provided the most favorable risk-benefit profile, demonstrating robust efficacy with no subjects experiencing eyelid ptosis. 3 Notably, the 40U dose of DAXI contains 0.18 ng of core neurotoxin, 2 similar to the onabotulinumtoxinA 20U dose.…”

“… 2 The DAXI dose was determined based on a Phase 2, dose-ranging clinical trial in which the 40U dose provided the most favorable risk-benefit profile, demonstrating robust efficacy with no subjects experiencing eyelid ptosis. 3 Notably, the 40U dose of DAXI contains 0.18 ng of core neurotoxin, 2 similar to the onabotulinumtoxinA 20U dose. 4 …”

Efficacy and Safety of Botulinum Toxin vs. Placebo in Depression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

“…Botulinum toxin type A (BTX-A), also known as onabotulinumtoxinA or Botox R , is widely known for its cosmetic efficacy in treating glabellar frown lines (8). It was estimated that more than 1 million cases of BTX-A treatment were reported annually in the United States (9).…”