AbobotulinumtoxinA for the Treatment of Moderate-to-Severe Glabellar Lines: A Randomized, Dose-Escalating, Double-Blind Study

September 2021 | Volume 20 | Issue 9 | Original Article | 980 | Copyright © September 2021


Published online August 16, 2021

John Joseph MDa, Amir Moradi MD MBAb, Z. Paul Lorenc MD FACSc, Kyle Coleman MDd, Glynis Ablon MD FAADe, Joely Kaufman-Janette MDf, Sue Ellen Cox MDg, Andrew Campbell MDh, Steven Dayan MDI, Anna-Karin Berg PhDj, Girish Munavalli MD MHS FACMSk

aClinical Testing of Beverly Hills, Encino, CA
bMoradi M.D., Vista, CA
cLorenc Aesthetic Plastic Surgery Center, New York, NY
dEtre Cosmetic Dermatology and Laser Center, New Orleans, LA
eAblon Skin Institute and Research Center, Manhattan Beach, CA
fSkin Research Institute, LLC, Coral Gables, FL
gAesthetic Solutions, PA, Chapel Hill, NC
hQuintessa Aesthetic Center – Ethiq2 Research, LLC, Mequon, WI
iDeNova Research, Chicago, IL
jGalderma, Uppsala, Sweden
kDermatology, Laser & Vein Specialists of the Carolinas, PLLC, Charlotte, NC

Abstract
Objective: To evaluate the efficacy and safety of AbobotulinumtoxinA (ABO) dose escalation in the correction of moderate-to-severe glabellar lines.
Design: Phase 2, 36-week, multicenter, randomized, dose-ranging, double-blind, placebo-controlled study.
Methods: Adults with moderate-to-severe glabellar lines received a single ABO treatment, dosed at 50, 75, 100, or 125 U, or placebo. Primary endpoint was week 4 composite ≥2-grade responder rate among those achieving a severity score of 0 (none) or 1 (mild) at maximum frown, evaluated using concurrent investigator and subject assessments. Secondary endpoints included ≥1-grade severity improvement, duration of effect, and reporting of treatment-emergent adverse events (TEAEs).
Results: Overall, 399 subjects were included (88.2% were female). Week 4 composite ≥2-grade ABO responder rate was 80.0% (50 U), 88.8% (75 U), 90.0% (100 U) and 95.1% (125 U), versus 2.6% with placebo (P<0.001). Responder rate (≥1-grade) ranged between 53% (50 U) and 69% (125 U) at week 24 and between 18% (50 U) and 31% (125 U) at week 36. Median time (weeks) to return to baseline severity/worse, among those scoring 0 (none) or 1 (mild), was 32.3 (50 U), 34.3 (75 U), 36.0 (100 U) and 36.6 (125 U), versus 23.7 (placebo). ABO-related TEAEs were reported in 4% of subjects (80% were mild). No seroconversion to ABO neutralizing antibodies was seen.
Conclusion: A single ABO treatment provided rapid and effective improvements in glabellar line severity at all doses. Higher doses tended to demonstrate elevated response rates and longer duration of effect. All ABO doses were well-tolerated with low TEAE incidence.

J Drugs Dermatol. 2021;20(9):980-987. doi:10.36849/JDD.6263

INTRODUCTION

Botulinum toxin type A treatment remains a cornerstone of facial aesthetic treatments.1,2 AbobotulinumtoxinA (ABO) has demonstrated efficacy, safety and subject satisfaction in the treatment of facial lines in randomized trials and real-world observational studies.3-6 ABO is available as Dysport® in the United States and Azzalure® in Europe (Ipsen Biopharm Limited, UK).7,8 The 50 Speywood unit (50 U) dose, currently licensed for correction of moderate-to-severe glabellar lines, has been shown to effectively reduce glabellar line severity for durations extending to 5 months.7-11 However, data suggest that higher doses of botulinum neurotoxin type-A products may lengthen treatment effect, without impacting safety.2,12,13 Joseph et al 2016 demonstrated that a single ABO 120 U treatment provided a prolonged treatment effect, compared with the 50 U