title: 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: BACKGROUND
  The 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.
  
  
  METHODS
  Patients with unwanted SMF were randomized to receive 1 or 2 mg/cm(2) 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.
  
  
  RESULTS
  Significantly 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/cm(2), 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/cm(2), 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/cm(2), 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/cm(2), respectively, and 91.6 % of the placebo recipients). Adverse events were mostly transient, mild to moderate in intensity, and localized to the treatment area.
  
  
  CONCLUSIONS
  The findings show ATX-101 to be an effective and well-tolerated pharmacologic treatment for SMF reduction.
authors.affiliation: McDiarmid-Hall Clinic, Derriford, Plymouth, UK.
authors.forename: James
authors.initials: J
authors.lastname: McDiarmid
authors.forename: Jesus Benito
authors.initials: JB
authors.lastname: Ruiz
authors.forename: Daniel
authors.initials: D
authors.lastname: Lee
authors.forename: Susanne
authors.initials: S
authors.lastname: Lippert
authors.forename: Claudia
authors.initials: C
authors.lastname: Hartisch
authors.forename: Blanka
authors.initials: B
authors.lastname: Havlickova
mesh_terms: D000328:Adult; D019440:Anti-Obesity Agents / Q000008:administration & dosage*; D015992:Body Mass Index; D057846:Cell-Penetrating Peptides / Q000008:administration & dosage*; D017326:Clinical Trials, Phase III as Topic; D003357:Cosmetic Techniques; D005260:Female; D006801:Humans; D007271:Injections, Intradermal; D008297:Male; D015337:Multicenter Studies as Topic; D017060:Patient Satisfaction; D016032:Randomized Controlled Trials as Topic; D050151:Subcutaneous Fat / Q000187:drug effects*
chemical_list: C587865:ATX-101 peptide; D019440:Anti-Obesity Agents; D057846:Cell-Penetrating Peptides