Kythera Biopharmaceuticals, Inc. announced that it has successfully completed a third phase II clinical study with ATX-101, a first-in-class adipolytic agent that is under investigation for the reduction of submental (‘under-the-chin’) fat. The phase IIb, randomized, double-blind, placebo-controlled, dose-ranging study showed ATX-101 was well tolerated and demonstrated statistically significant efficacy as compared with placebo. The study enrolled a total of 129 subjects and was conducted across 10 dermatology and plastic surgery centres in the United States. Multiple clinician and patient endpoints were assessed, as well as MRI to objectively quantify fat reduction. The study tested two drug-dosing regimens (1 and 2 mg/cm2).
In this study, ATX-101 demonstrated statistically significant (p<0.05) reductions in submental fat as compared with placebo as assessed by all measures: a validated clinician scale, patient reported outcome (PRO) scale, and Magnetic Resonance Imaging (MRI) measurement for both fat volume and thickness. Adverse events were primarily mild to moderate, and were transient. In addition, a statistically significant difference versus placebo was also shown on other PRO measures, including instruments measuring subject satisfaction, patient impact and chin attractiveness.
"An injectable treatment, with promising results in the reduction of submental fat, expands options for aesthetic patients seeking minimally invasive treatment,” said V. Leroy Young, MD, FACS, a plastic surgeon in private practice in St. Louis and an investigator in the study. “Reductions of fat in a targeted area such as the chin can have substantial impact on both appearance and patient satisfaction, and this is borne out in the photographic and MRI assessments in the phase IIb data.”
“We are very pleased with the results and the meaningful improvements the subjects achieved. This is truly a breakthrough for aesthetic medicine, bringing together clinician and patient reported outcomes on validated scales, along with an objective and quantifiable endpoint,” said Patricia Walker, MD, PhD, Kythera’s chief medical officer. “We look forward to presenting the data at an upcoming scientific meeting.”
Kythera has done extensive development work on ATX-101 for submental fat and has completed seven clinical trials and treated more than 350 subjects. In two previously conducted ex-US phase II studies on 155 patients, ATX-101 was well-tolerated and yielded statistically significant reduction of submental fat compared to placebo based on clinician and patient assessments. Results observed from the current pPhase IIb study confirmed the observations made in previous Phase II clinical trials. Phase III studies of ATX-101 were initiated in late 2010 in Europe in collaboration with Bayer HealthCare’s dermatology unit Intendis, which has licensed rights to ATX-101 outside of the US and Canada.
“These results are exciting,” said Gary Monheit, MD, a dermatologist in private practice in Alabama and an investigator in this study. “ATX-101 has the potential to expand facial rejuvenation for aesthetic patients, filling an existing gap for minimally invasive submental fat reduction.”
ATX-101 is a first-in-class injectable drug being studied for the reduction of small volumes of fat, including submental fat. It is based on an endogenous molecule with unique features including selectivity for adipocytes and rapid clearance. This minimally invasive procedure, done with little or no anesthetic, has the promise to yield consistent and meaningful clinical results. Clinical studies to date have demonstrated that ATX-101 is well-tolerated and may effectively reduce localized fat in the submental area. Three randomized, double-blind, placebo-controlled, Phase II studies with ATX-101 in the reduction of submental fat and four Phase I pharmacokinetic, histology, lipid and tolerability studies have been successfully completed.
Submental fat is localized subcutaneous fat located immediately beneath the chin and jawline. In the rapidly growing market of minimally invasive, non-surgical facial rejuvenation, the reduction of facial fat to restore and reshape the jawline remains one of the largest unmet patient needs. According to a recent national, multi-centre, clinical evaluation of more than 385 Botox and dermal filler patients, 78% of patients had a measurable excess of submental fat. Currently, there are no FDA approved drugs to reduce excess localized fat.
Kythera Biopharmaceuticals, Inc. is a privately held, clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of novel prescription products for the aesthetic market.