Safety and Efficacy of Recombinant Botulinum Toxin Type A for Moderate-to-severe Glabellar Lines: A Multicenter Randomized Controlled Trial.

[BACKGROUND] YY001 (Retoxin ®), the first global recombinant botulinum toxin type A (rBoNT/A) tested in humans, contains a pure 150-kDa core neurotoxin identical to natural BoNT/A (nBoNT/A). This study aimed to evaluate the safety and preliminary efficacy of YY001 in humans for moderate-to-severe glabellar lines.

[METHODS] Preclinical assessments comprised homology modeling, biochemical and pharmacological evaluation, and multispecies toxicology. In this phase I multicenter double-blind, randomized, dose-ranging, vehicle- and active- controlled trial, participants (n=50) with moderate-to-severe glabellar lines were randomized 1:1:1:1:1 to receive intramuscular injection of YY001 at 10, 20 and 30 U, Botox ® at 20 U, or vehicle. The primary endpoint encompassed the incidence of adverse events (AEs), serious AEs, injection site reactions and clinically significant laboratory changes within 28 days post-injection, with exploratory follow-up to 168 days.

[RESULTS] The YY001's structure and biological activities are highly consistent with those of nBoNT/A. In this trial, no drug-related AEs were observed in the tested 10-30 U of YY001. At day 28, the response rate by investigator's live assessment was 60% for 10 U of YY001, 80% for 20 U of YY001, 90% for 30 U of YY001, 70% for 20 U of Botox ®, and 0% for the vehicle, while the proportion of subjects with none or mild glabellar lines at maximum frown was 80%, 90%, 100%, 80%, and 0%, respectively.

[CONCLUSIONS] The first rBoNT/A (YY001) in human study demonstrated a favorable safety and tolerability profile (dose-independent) at doses of 10, 20 and 30 U in Chinese subjects with moderate-to-severe glabellar lines. It also showed dose-dependent efficacy benefit.Trial Registration: ChinaDrugTrials.org.cn identifier: CTR20221419.