April 2020 HSC Section 4 - Plastic and Reconstructive Problems

ATX - 1 0 1 FOR M I LD AND EXTR EME SMF

Traditional procedures to reduce SMF include surgery and liposuction, but these methods can present complications and/or unfavorable results. 4 Deoxycholic acid, which naturally occurs in the body as a bile salt that emulsi fi es dietary fats, has adipo- cytolytic properties when injected into fat tissue. 5,6 Based on results from multiple Phase 3 trials, 7 – 10 ATX-101 (deoxycholic acid injection; Kybella/ Belkyra [Canada, Australia, Europe, and South Korea]; Kythera Biopharmaceuticals, Inc., Westlake Village, California, an af fi liate of Allergan plc, Dublin, Ireland) is approved for reduction of moderate to severe convexity or fullness associated with SMF. 11,12 However, individuals with mild or extreme SMF may also be dissatis fi ed with the appearance of their submental area and seek inter- vention from a physician. The current study evalu- ated the ef fi cacy and safety of ATX-101 treatment in the previously unstudied populations of subjects with mild or extreme SMF. Eligible subjects were aged 18 to 65 years with mild or extreme SMF according to the validated Clinician- Reported SMF Rating Scale, with grades of absent (0), mild (1), moderate (2), severe (3), and extreme (4). 8,9 Subjects also had to be dissatis fi ed with the appearance of their face/chin, with ratings of 0, 1, or 2 on the Subject Self-Rating Scale (SSRS), which includes ratings of extremely dissatis fi ed (0), dissatis fi ed (1), slightly dis- satis fi ed (2), neither dissatis fi ed nor satis fi ed (3), slightly satis fi ed (4), satis fi ed (5), and extremely satis fi ed (6). 8,9 Body weight had to be stable for $ 6 months. Key exclusion criteria included body mass index (BMI) >40 kg/m 2 ; previous treatment of SMF with liposuction, surgery, or lipolytic agents; previous treatment of the neck/chinwith radiofrequency, lasers, chemical peels, dermal fi llers (within 12 months of randomization), or botulinum toxin (within 6 months of randomization); sensitivity to topical/local anes- thetics or any component of the study drug; enlarge- Materials and Methods Subjects

ment of the submental area for any reason other than SMF; current/past symptoms of dysphagia, trauma, or any medical condition that would interfere with the subject ’ s ability to undergo study procedures/assessments; or excessive skin laxity (including a grade of severe [4] based on clinician assessment using the Submental Skin Laxity Grade scale). 8,9 This randomized, double-blind, placebo-controlled Phase 3b trial (NCT02035267) was conducted at 8 sites in the United States between January 2014 and June 2015 in accordance with the International Con- ference on Harmonization Guideline for Good Clini- cal Practice and the principles of the 1975 Declaration of Helsinki. The protocol was approved by central and local institutional reviewboards. All subjects provided written informed consent. Subjects were strati fi ed according to baseline SMF severity (mild or extreme) and randomized 2:1 to receive ATX-101 (area-adjusted dose: 2 mg/cm 2 ) or placebo as subcutaneous injections into pre- platysmal fat. Up to 10 mL of ATX-101 could be injected at each treatment, and subjects could receive # 6 treatments (every 28 6 5 days). Subjects could receive <6 treatments because of ef fi cacy (insuf fi cient SMF to safely inject study drug or subject satisfaction with SMF reduction), lack of tolerability, or administrative decision by the inves- tigator or sponsor. Pretreatment comfort measures, which typically included ice, topical/injectable anesthetics, and/or oral analgesics, were used at the discretion of the clinician. Subjects assessed their SMF according to the vali- dated Patient-Reported SMF Rating Scale, where the amount of chin fat is graded as none (0), slight (1), moderate (2), large (3), or very large (4). 8,9 Ef fi cacy end points, evaluated at 12 weeks after last treatment, included the percentage of subjects who achieved a $ 1-grade improvement in SMF from baseline based on clinician assessment (CR-1 response), subject assessment (PR-1 response), or Trial Design Outcome Measures

DE RMATOLOG I C S URG E RY

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