IncobotulinumtoxinA Demonstrates Safety and Prolonged Duration of Effect in a Dose-Ranging Study for Glabellar Lines

October 2021 | Volume 20 | Issue 10 | Original Article | 1052 | Copyright © October 2021


Published online September 28, 2021

Martina Kerscher MD PhDa, Sabrina Fabi MDb, Tanja Fischer MD PhDc, Michael Gold MDd, John Joseph MDe, Welf Prager MDf, Berthold Rzany MD ScMg, Steve Yoelin MDh, Susanna Roll Dr. medI, Gudrun Klein PhDi, Corey Maas MD PhDj

aUniversit t Hamburg, Hamburg, Germany
bCosmetic Laser Dermatology, San Diego, CA
cHaut- & Lasercentrum, Potsdam, Germany
dGold Skin Care Center, Tennessee Clinical Research Center, Nashville, TN
eJohn Joseph MD, Private Practice, Beverly Hills, CA
fPrager and Partner Dermatologische Praxis, Hamburg, Germany
gHaut rzte RZANY&HUND, Berlin, Germany
hMedical Associates, Inc., Newport Beach, CA
iMerz Pharmaceuticals GmbH, Frankfurt am Main, Germany
jThe Maas Clinic, San Francisco, CA

Abstract
Background: To further explore clinical trial results indicating increasing doses of botulinum toxin A prolong duration of effect, a 2-stage, phase 2, randomized, double-blind study investigated the duration of effect and safety of incobotulinumtoxinA (INCO; Xeomin®, Bocouture®) doses higher than the US Food and Drug Administration-approved 20 units (U) for glabellar frown lines (GFL). The stage 1 primary efficacy and safety results were reported previously. Here, we report the results of the final analysis (stage 1 and 2), including primary and secondary efficacy and safety endpoints.
Methods: A total of 241 subjects with moderate-to-severe GFL were randomized to receive a single treatment with 20 (N=61), 50 (N=60), 75 (N=61), or 100U (N=59) INCO. The primary efficacy endpoint was duration of ≥ 1-point improvement from baseline assessed by investigator at maximum frown on the Facial Wrinkle Scale.
Results: The median duration of effect was 175 days for the 20U group (95% CI 142, 185), 185 days for the 50U group (95% CI 182, 205), 210 days for the 75U group (95% CI 182, 217), and 215 days for the 100U group (95% CI 183, 237). The incidence of treatment-related adverse events was low across all doses and there were no treatment-related serious adverse events.
Conclusions: These results demonstrate that all INCO doses were well tolerated, consistent with the known safety profile of 20U, and increasing dose prolongs the duration of effect for GFL.

J Drugs Dermatol. 2021;20(10):1052-1060. doi:10.36849/JDD.6377

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INTRODUCTION

IncobotulinumtoxinA (INCO; Xeomin®, Bocouture®; Merz Pharmaceuticals GmbH, Frankfurt am Main, Germany) is approved in the United States and worldwide markets for treating glabellar frown lines (GFL) at a dose of 20 units (U) and in the European Union at a dose of 20–30 U. Phase 3 studies that used 20U of INCO demonstrated the duration of effect lasts for at least 4 months.1–3

There is an increasing demand for a longer duration of effect from botulinum toxin A (BoNT/A) products. INCO is unique among commercially available products in that it does not contain unnecessary bacterial proteins,4–6 which may reduce immunogenicity.7,8,9 The manufacturing process, which includes a 2-step chromatographic purification procedure, yields only the active 150kDa molecule, giving INCO the lowest protein load of available BoNT/A formulations, which is a consideration with overall increasing doses used in aesthetics.7,10–14

A randomized, double-blind, investigator-initiated study showed a strong dose-response relationship with doses of 20, 60, and 100U INCO exhibiting a median duration of effect of 120, 180, and 270 days, respectively.15 Adverse events (AEs) with the higher doses were mild and consistent with the known safety profile of 20U INCO.

A 2-stage dose-ranging phase 2 trial was conducted to assess the safety and duration of escalating INCO doses (20, 50, 75U in stage 1 and 20 and 100U in stage 2) for up to 360 days. The stage 1 primary efficacy and safety results were reported previously.16 Here, we report the results for the full cohort, including the primary and secondary endpoints for efficacy and safety.