Results from a Pooled Analysis of Two European, Randomized, Placebo-Controlled, Phase 3 Studies of ATX-101 for the Pharmacologic Reduction of Excess Submental Fat

Abstract

BackgroundThe injectable adipocytolytic drug ATX-101 is the first nonsurgical treatment for the reduction of submental fat (SMF) to undergo comprehensive clinical evaluation. This study aimed to confirm the efficacy and safety of ATX-101 for SMF reduction through a post hoc pooled analysis of two large phase 3 studies.MethodsPatients with unwanted SMF were randomized to receive 1 or 2 mg/cm2 of ATX-101 or a placebo injected into their SMF during a maximum of four treatment sessions spaced approximately 28 days apart, with a 12-week follow-up period. The proportions of patients with reductions in SMF of one point or more on the Clinician-Reported SMF Rating Scale (CR-SMFRS) and the proportions of patients satisfied with the appearance of their face and chin [Subject Self-Rating Scale (SSRS) score ≥4] were reported overall and in subgroups. Other efficacy measures included improvements in the Patient-Reported SMF Rating Scale (PR-SMFRS), calliper measurements of SMF thickness, and assessment of skin laxity [Skin Laxity Rating Scale (SLRS)]. Adverse events and laboratory test results were recorded.ResultsSignificantly greater proportions of the patients had improvements in clinician-reported measures (≥1-point improvement in CR-SMFRS: 58.8 and 63.8 % of the patients who received ATX-101 1 and 2 mg/cm2, respectively, and 28.6 % of the placebo recipients; p < 0.001 for both ATX-101 doses vs. placebo) and patient-reported measures (≥1-point improvement in PR-SMFRS: 60.0 and 63.1 % of the patients who received ATX-101 1 and 2 mg/cm2, respectively, vs. 34.3 % of the placebo recipients; p < 0.001 for both), analyzed alone or in combination, with ATX-101 versus placebo. These improvements correlated moderately with patient satisfaction regarding face and chin appearance (SSRS score ≥4: 60.8 and 65.4 % of the patients who received ATX-101 1 and 2 mg/cm2, respectively, vs. 29.0 % of the placebo recipients; p < 0.001 for both). In this study, ATX-101 was effective irrespective of gender, age, or body mass index. Reduction in SMF with ATX-101 was confirmed by calliper measurements (p < 0.001 for both doses vs. placebo) and generally did not lead to worsening of skin laxity (SLRS improved or was unchanged: 91.3 and 90.5 % of the patients who received ATX-101 1 and 2 mg/cm2, respectively, and 91.6 % of the placebo recipients). Adverse events were mostly transient, mild to moderate in intensity, and localized to the treatment area.ConclusionThe findings show ATX-101 to be an effective and well-tolerated pharmacologic treatment for SMF reduction.Level of Evidence IThis journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

ATX-101 for reduction of submental fat

“…No treatment was necessary, all symptoms such as asymmetric smile resolved without treatment [36]. This side effect can be prevented by exact injection technique ensuring a distance between injection site and nerve branch [37,38].…”

“…Primary end points of both trials were CR-SMFRS and subject self-rating scale. The secondary end points were skin laxity (skin laxity rating scale [SLRS]), caliper measurements of SMF in millimeters, PR-SMSRS, PR-SMFIS and safety outcome measures ( Table 1) [36].…”

“…Phase II, multicenter, randomized, double-blind, placebo-controlled, parallel-group study of the safety and efficacy of ATX-101 (NCT00618618) . Interventional nonrandomized long-term, follow-up study of patients who completed Phase III trials of ATX-101-10-16 or ATX-101-10-17 (NCT02052622) [31][32][33][34][35][36][37][38][39].…”

“…In an analysis from the pooled data of the two Phase III trials from Europe, ATX-101 proved to be an effective and well-tolerated pharmacological treatment of undesired SMF ( Table 2) [36].…”

“…Regrowth of adipose tissue after PC/DC injection of lipomas [41] has not been observed in SMF ATX-101 trials [36][37][38][39]. Table 4 provides a summary of adverse effects.…”