REFINE-1, a Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial With ATX-101, an Injectable Drug for Submental Fat Reduction

BACKGROUND ATX-101, an injectable form of deoxycholic acid, is approved in the United States and Canada for submental fat (SMF) reduction. OBJECTIVE To report results of REFINE-1, a randomized, double-blind, placebo-controlled, Phase 3 trial investigating the efficacy and safety of ATX-101. METHODS Subjects dissatisfied with their moderate or severe SMF received ATX-101 (2 mg/cm2) or placebo. Coprimary outcome measures were composite ≥1-grade and ≥2-grade improvements in clinician-assessed and subject-assessed SMF severity using validated scales at 12 weeks after last treatment. Magnetic resonance imaging (MRI) provided an objective measure of submental volume reduction. Patient-reported outcomes were assessed. RESULTS Among 256 ATX-101–treated and 250 placebo-treated subjects, a ≥1-grade composite response was achieved in 70.0% and 18.6%, and a ≥2-grade composite response in 13.4% and 0%, respectively (p < .001 for both). The proportion of MRI responders was more than 8 times higher with ATX-101 than placebo (46.3% vs 5.3%; p < .001). ATX-101–treated subjects reported improvement in the psychological impact of SMF and satisfaction with treatment (p < .001 for all assessments vs placebo). Of note, 55% and 75% of ATX-101–treated subjects reported 1-grade improvement in clinician-assessed SMF after 2 and 4 treatments, respectively. Adverse events (primarily localized to the injection site) were mostly mild or moderate, and transient. Marginal mandibular nerve paresis reported in 4.3% of ATX-101–treated subjects (1.0% of all ATX-101 treatment sessions) was mostly mild, transient, and resolved without sequelae. CONCLUSION ATX-101 is a safe and efficacious, first-in-class, injectable drug for SMF reduction.