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)

Jean D Carruthers, Steve Fagien, John H Joseph, Shannon D Humphrey, Brian S Biesman, Conor J Gallagher, Yan Liu, Roman G Rubio, SAKURA 1 and SAKURA 2 Investigator Group, SAKURA 1 and SAKURA 2 Investigator Group includes the following, Joel L Cohen, Stephen Ho, Sue Ellen Cox, John Soderberg, Arthur Swift, Daniel Borsuk, Vasilios Papanastasiou, Ava Shamban, Soheil Simzar, Vince Bertucci, Brittany Waller, Charles Boyd, Molly Katz, Lauren Churchill, Stacy Smith, Cheryl Burgess, Karan Dhir, Zoe Draelos, Michael Draelos, Nathan Rosen, Channy Muhn, Ashish C Bhatia, Shraddha Desai, Te-Shao Hsu, Christopher T Kelly, Brandice M Brazell, Jeanine Downie, Bruce Katz, Marianne Woody, Mary Lupo, Skylar Souyoul, Kavita Mariwalla, Joseph Eviatar, Wm Philip Werschler, Scott Schade, Richard G Glogau, Derek Jones, Jeanette M Black, Naissan Wesley, Joely Kaufman-Janette, Joel Schlessinger, Jacqueline Hall, Shea Perillo, Jeffrey Dover, Laurel Morton, Nowell Solish, Gary Monheit, Heidi Essig, Steve Yoelin, Steve Yoelin, Jean D Carruthers, Steve Fagien, John H Joseph, Shannon D Humphrey, Brian S Biesman, Conor J Gallagher, Yan Liu, Roman G Rubio, SAKURA 1 and SAKURA 2 Investigator Group, SAKURA 1 and SAKURA 2 Investigator Group includes the following, Joel L Cohen, Stephen Ho, Sue Ellen Cox, John Soderberg, Arthur Swift, Daniel Borsuk, Vasilios Papanastasiou, Ava Shamban, Soheil Simzar, Vince Bertucci, Brittany Waller, Charles Boyd, Molly Katz, Lauren Churchill, Stacy Smith, Cheryl Burgess, Karan Dhir, Zoe Draelos, Michael Draelos, Nathan Rosen, Channy Muhn, Ashish C Bhatia, Shraddha Desai, Te-Shao Hsu, Christopher T Kelly, Brandice M Brazell, Jeanine Downie, Bruce Katz, Marianne Woody, Mary Lupo, Skylar Souyoul, Kavita Mariwalla, Joseph Eviatar, Wm Philip Werschler, Scott Schade, Richard G Glogau, Derek Jones, Jeanette M Black, Naissan Wesley, Joely Kaufman-Janette, Joel Schlessinger, Jacqueline Hall, Shea Perillo, Jeffrey Dover, Laurel Morton, Nowell Solish, Gary Monheit, Heidi Essig, Steve Yoelin, Steve Yoelin

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.

Trial registration: ClinicalTrials.gov NCT03014635 NCT03014622.

Figures

Fig. 1.
Fig. 1.
Disposition of subjects in SAKURA 1 and SAKURA 2 studies.
Fig. 2.
Fig. 2.
Proportion of subjects with glabellar line severity of none or mild at maximum frown assessed by investigators using the Investigator Global Assessment–Frown Wrinkle Severity (IGA-FWS) scale or by subjects using the Patient Frown Wrinkle Severity (PFWS) scale. (Above) SAKURA 1 study; (below) SAKURA 2 study.
Fig. 3.
Fig. 3.
Proportion of subjects with an improvement in Global Aesthetic Improvement Scale score at maximum frown. In the two studies, investigator ratings showed that the proportion of subjects who were improved, much improved, or very much improved in the DaxibotulinumtoxinA for Injection group was 98.0 percent and 98.0 percent at week 4, and 43.1 percent and 44.2 percent at week 24, compared with placebo group values of 3.1 percent and 3.0 percent at week 4, and 0 percent and 1.1 percent at week 24. (Above) SAKURA 1 study; (below) SAKURA 2 study.
Fig. 4.
Fig. 4.
Duration for which glabellar line severity of none or mild at maximum frown was maintained after DaxibotulinumtoxinA for Injection treatment in SAKURA 1 and SAKURA 2 studies according to wrinkle severity assessments from both investigators and subjects [i.e., on both the Investigator Global Assessment–Frown Wrinkle Severity (IGA-FWS) scale and the Patient Frown Wrinkle Severity (PFWS) scale].
Fig. 5.
Fig. 5.
Time for glabellar line severity at maximum frown to return to baseline levels after DaxibotulinumtoxinA for Injection treatment in SAKURA 1 and SAKURA 2 studies according to wrinkle severity assessments from both investigators and subjects [i.e., on both the Investigator Global Assessment–Frown Wrinkle Severity (IGA-FWS) scale and the Patient Frown Wrinkle Severity (PFWS) scale].
Fig. 6.
Fig. 6.
Subject treated with 40 U of DaxibotulinumtoxinA for Injection showing a 2-point reduction in glabellar line severity at maximum frown at week 4 that was sustained through week 24 according to both investigator and subject ratings. A 1-point reduction in glabellar line severity was sustained until at least week 36 according to investigator ratings and until at least week 32 according to subject ratings. Investigators used the Investigator Global Assessment–Frown Wrinkle Severity (IGA-FWS) scale and subjects used the Patient Frown Wrinkle Severity (PFWS) scale.
Fig. 7.
Fig. 7.
Subject global satisfaction with treatment at week 4. The proportion of subjects who were satisfied or very satisfied was 89.8 percent and 91.1 percent in the DaxibotulinumtoxinA for Injection groups (in the SAKURA 1 and SAKURA 2 studies, respectively) compared with 2.1 percent and 4.0 percent in the placebo groups.

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