Reduction of Unwanted Submental Fat With ATX-101 (Deoxycholic Acid), an Adipocytolytic Injectable Treatment

Results From a Phase III, Randomized, Placebo-Controlled Study

B. Rzany; T. Griffiths; P. Walker; S. Lippert; J. McDiarmid; B. Havlickova

Disclosures

The British Journal of Dermatology. 2014;170(2):445-453. 

In This Article

Abstract and Introduction

Abstract

Background Unwanted submental fat (SMF) is aesthetically unappealing, but methods of reduction are either invasive or lack evidence for their use. An injectable approach with ATX-101 (deoxycholic acid) is under investigation.

Objectives To evaluate the efficacy and safety of ATX-101 for the reduction of unwanted SMF.

Methods In this double-blind, placebo-controlled, phase III study, 363 patients with moderate/severe SMF were randomized to receive ATX-101 (1 or 2 mg cm−2) or placebo injections into their SMF at up to four treatment sessions ~28 days apart, with a 12-week follow-up. The co-primary efficacy endpoints were the proportions of treatment responders [patients with ≥ 1-point improvement in SMF on the 5-point Clinician-Reported Submental Fat Rating Scale (CR-SMFRS)] and patients satisfied with their face and chin appearance on the Subject Self-Rating Scale (SSRS). Secondary endpoints included skin laxity, calliper measurements and patient-reported outcomes. Adverse events were monitored.

Results Significantly more ATX-101 recipients met the primary endpoint criteria vs. placebo: on the clinician scale, 59·2% and 65·3% of patients treated with ATX-101 1 and 2 mg cm−2, respectively, were treatment responders vs. 23·0% for placebo (CR-SMFRS;P < 0·001); on the patient scale, 53·3% and 66·1%, respectively, vs. 28·7%, were satisfied with their face/chin appearance (SSRS;P < 0·001). Calliper measurements showed a significant reduction in SMF (P < 0·001), skin laxity was not worsened and patients reported improvements in the severity and psychological impact of SMF with ATX-101 vs. placebo. Most adverse events were transient and associated with the treatment area.
Conclusions ATX-101 was effective and well tolerated for nonsurgical SMF reduction.

Introduction

Loss of definition in the submental area and an obtuse cervicomental angle may result from unwanted submental fat (SMF), which is considered aesthetically unappealing.[1,2] Undesirable SMF can have a psychological impact, particularly because it is suggestive of ageing or obesity.[1–3] This SMF may derive from a genetic predisposition,[4] ageing[5] and/or lifestyle and diet.[4,5]

Unwanted SMF can be addressed surgically as part of a platysmaplasty (with or without face-lift) or liposuction of the neck and chin.[1,6] These procedures are effective but may not be suitable for all patients,[5] and the need for anaesthesia, an operating room and qualified staff substantially increases costs and risks.[1] Liposuction, with or without an accompanying energy device,[7,8] is the most commonly used intervention and, although less invasive than platysmaplasty or face-lift, may result in postoperative complications and an unfavourable result, such as prominent anterior platysmal banding.[6,9] Furthermore, invasive procedures may require significant recovery times, occasionally up to 1 year.[10] Nonsurgical energy devices exist,[7] but clinical evidence supporting their efficacy is limited. An efficient, evidence-based, minimally invasive treatment approach may be an appropriate option for reducing unwanted SMF.

Unregulated injectables for localized fat reduction, often based on a combination of phosphatidylcholine and deoxycholate, have been available for some time. Deoxycholate, and not phosphatidylcholine, has been shown to be the active lytic agent in these preparations.[11] ATX-101, the subject of this study, is an injectable proprietary formulation of synthetically derived deoxycholic acid (DCA), which disrupts adipocyte membranes leading to irreversible cell breakdown (adipocytolysis).[12] After adipocytolysis, a mild inflammatory response is induced, with macrophage recruitment and phagocytosis,[12–14] through which cellular debris is cleared over time. Plasma lipid levels show no meaningful increase over time after ATX-101 treatment.[13] DCA does not accumulate in adipose tissue, owing to rapid clearance facilitated by protein binding, which also attenuates the action of DCA in nonlipid-rich tissues such as muscle and bone.[12]

ATX-101 demonstrated efficacy in the reduction of SMF with appropriate tolerability in phase I and II studies,[15–18] and is the first pharmacological adipocytolytic formulation to be investigated in large-scale randomized, controlled clinical studies. Results from the first European phase III study of ATX-101 for the reduction of unwanted SMF are presented here.

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