Sequential Administration of TrenibotulinumtoxinE and OnabotulinumtoxinA for Glabellar Lines: a Phase 1 Evaluation

BACKGROUND: Botulinum neurotoxin type A (BoNT/A) is widely used to treat facial wrinkles. Certain individuals considering neurotoxin treatments may hesitate to try BoNT/A products due to uncertain outcomes. TrenibotulinumtoxinE (trenibotE), a botulinum neurotoxin serotype E, has a distinct pharmacological profile from BoNT/A. OBJECTIVES: This Phase 1 study evaluated the safety and efficacy of sequential administration of trenibotE followed by onabotulinumtoxinA (onabotA) for the treatment of moderate-to-severe glabellar lines (GL). METHODS: Participants received a single administration of placebo or trenibotE 700 U on Day 1. On Day 30, eligible participants received a single administration of onabotA 20 U and were followed through Day 150. Investigators and participants utilized the Facial Wrinkle Scale (FWS) to assess GL at maximum frown during each visit. The primary endpoint was investigator-assessed achievement of None or Mild on the FWS at maximum frown at Day 60. Safety and immunogenicity were evaluated. RESULTS: On Day 1, 90 participants received placebo or trenibotE. On Day 30, 85 participants received onabotA. Responder rates at Day 60 were similar between participants who initially received placebo or trenibotE. Peak responder rates of None or Mild GL severity were similar for trenibotE at Day 7 and onabotA at Day 60 (30 days post-onabotA). Most treatment-emergent adverse events were mild, nonserious, and unrelated to study treatment. No participants developed treatment-emergent binding or neutralizing antibodies to trenibotE or onabotA. CONCLUSIONS: Sequential administration of trenibotE followed by onabotA as studied identified no new safety concerns and may be a potential treatment strategy for moderate-to-severe GL. PLAIN-TEXT SUMMARY: In this study, treatment with fast-acting trenibotulinumtoxinE followed 30 days later by onabotulinumtoxinA generally improved facial wrinkles (glabellar lines), as assessed by both patients and clinicians. No new safety concerns were identified.