Date: 2013-02-01
Type of information: Initiation of the trial
phase: 3
Announcement: initiation of the trial
Company: Bayer (Germany)
Product: ATX-101 (proprietary formulation of synthetic sodium deoxycholate)
Action
mechanism: ATX-101 is a potential first-in-class injectable drug candidate under clinical investigation for the reduction of localized fat. ATX-101 is a proprietary formulation of synthetic sodium deoxycholate, a well-characterized endogenous compound that is present in the body to promote the natural breakdown of dietary fat. ATX-101 reduces subcutaneous fat through localized fat cell membrane disruption followed by elimination from the treated area. This mechanism may enable a non-surgical alternative for the reduction of unwanted subcutaneous fat. Clinical studies to date have demonstrated that ATX-101 is well tolerated and may effectively reduce localized fat in the submental (under the chin) area.
In August 2010, Bayer Consumer Care AG signed a licensing and collaboration development agreement with Kythera, thereby obtaining commercialization rights to the injectable adipolytic agent ATX-101 outside of the US and Canada. Kythera and Bayer are collaborating on the development of ATX-101 in Europe.
Disease: reduction of localized fat under the chin (submental fat)
Therapeutic area: Aesthetic area
Country: United Kingdom, France, Germany, Belgium, Spain and Italy
Trial
details: The two identical Phase III multi-center, randomized, double-blind, placebo-controlled trials enrolled 723 patients and were conducted in 57 centers across the Belgium, Germany, France, United Kingdom, Italy and Spain. In both trials, patients received one of two dosing regimens (1 mg/cm2 or 2 mg/cm2) or placebo, administered monthly into the submental fat area for up to four treatment cycles, and were followed up for 12 weeks post treatment. Efficacy of ATX-101 compared to placebo was assessed by a validated 5-point Clinician-Reported Submental Fat Rating Scale (CR-SMFRS). The Patient-Reported Outcomes (PRO) were evaluated on the basis of a 7-point Subject Satisfaction Rating Scale (SSRS), a validated 5-point Patient-Reported Submental Fat Rating Scale (PR-SMFRS) and a Patient-Reported Submental Fat Impact Scale (PR-SMFIS). Calipers, an objective measure of submental fat thickness, also were used to assess the reduction of submental fat.
Latest
news: * On February 1, 2013, Bayer has presented at the International Master Course on Aging Skin (IMCAS) in Paris, the results of two pivotal European Phase-III studies with ATX-101, an investigational injectable drug for the reduction of unwanted fat deposits under the chin known as submental fat (SMF). Based on efficacy measures, analysis of the Phase-III data demonstrated that ATX-101 significantly reduced SMF compared to placebo. * On April 25, 2012, Bayer has announced the successful completion of two pivotal European Phase III clinical trials with ATX-101, an injectable drug for the reduction of unwanted fat under the chin. In a top-line analysis of the study data, ATX-101 demonstrated in the primary endpoint statistically significant efficacy (p<0.001) compared to placebo in the reduction of the fat, as assessed by two primary measures: a 5-point Clinician-Reported Submental Fat Rating Scale (CR-SMFRS) and a 7-point Subject Satisfaction Rating Scale (SSRS). In addition, in both pivotal trials, ATX-101 demonstrated statistically significant efficacy (p<0.001) compared to placebo as evaluated by secondary Patient-Reported Outcome (PRO) measures. These improvements were also confirmed by reductions in submental fat thickness measured using calipers (p<0.025). If approved, ATX-101 will be the first in a new class of aesthetic drugs to reduce fat under the chin without surgery. The clinical development of ATX-101 is a joint effort by Bayer and Kythera and both trials were initiated on January 2011.
ATX-101 reduces subcutaneous fat by localized fat-cell-membrane disruption followed by elimination from the treated area, and is the first drug undergoing comprehensive evaluation in a clinical trial setting for the reduction of submental fat. Compared to placebo, ATX-101 led to significant improvements in clinician-reported measurements of SMF, supported by objective caliper measurements of SMF thickness. Moreover, patients reported significant reductions in SMF with ATX-101 compared to placebo, and were significantly more satisfied with their chin appearance and their treatment as a result. These positive Phase-III results confirm earlier findings of two Phase-II studies demonstrating positive results for ATX-101. Up to now, the aesthetic correction of fatty deposits under the chin has predominantly been performed using surgical procedures involving possible undesirable side effects for the patient. These results were also presented at the IMCAS as poster.
Results from both Phase III trials reflect the positive findings already observed in previous Phase II trials, where ATX-101 was well tolerated and yielded statistically significant reduction of unwanted submental fat compared to placebo, based on the assessments of clinicians, patients and objective measurements.
Adverse events were primarily mild to moderate and transient. The most common adverse events were pain, swelling, numbness, bruising and induration. These adverse events were limited to the injection site; most were temporally associated with treatment. No systemic treatment-related adverse events were reported. The complete data set analysis will be available in the course of 2012.
