A Multicenter, Randomized, Double-Blind Phase 2B Study of ATX-101 in the Reduction of Submental Fat Using Investigator, Subject, and Magnetic Resonance Imaging Assessments
Goals/Purpose:
To evaluate the efficacy and tolerability of ATX-101, an investigational-stage injectable drug for the reduction of submental fat (SMF). Excess submental fat commonly manifests as the appearance of an aesthetically unappealing “double chin” and can negatively impact overall facial appearance. The accumulation of SMF is often associated with familial predisposition, aging or weight gain and can be resistant to diet or exercise measures. There are no FDA-approved pharmacologic therapies for the reduction of SMF; current treatment options are limited to liposuction or necklifts. ATX-101 is a proprietary formulation of synthetically-derived sodium deoxycholate, a well-characterized endogenous molecule that, when injected into subcutaneous fat, causes localized adipocytolysis while leaving surrounding tissue largely unaffected. In this Phase 2B study, the clinical potential for ATX-101 in the reduction of SMF was evaluated by clinicians, subjects and magnetic resonance imaging (MRI).
Methods/Technique:
In this double-blind, placebo-controlled Phase 2B study conducted across 10 dermatology and plastic surgery centers in the United States, 129 subjects with moderate or severe SMF considered undesirable were randomly assigned to receive injections of ATX-101 (1 or 2 mg/cm2) or placebo into the pre-platysmal submental fat for up to 6 treatment sessions at 4-week intervals. Clinician assessment of SMF severity was performed using the validated Clinician-Reported Submental Fat Rating Scale (CR-SMFRS) at all treatment visits and at 4 and 12 weeks after the last treatment (week 24 and week 32, respectively). Subject self-assessment of the severity and impact of SMF was performed at baseline, week 16 and 12 weeks after the last treatment (week 32) using the validated Patient-Reported Submental Fat Rating Scale (PR-SMFRS) and Patient-Reported Submental Fat Impact Scale (PR-SMFIS), respectively. An objective assessment of SMF volume and thickness was developed using a midline sagittal slice analysis of MRI. Adverse events (AEs) and changes in vital signs and laboratory parameters were recorded throughout the study.
Results/Complications:
At the 2 mg/cm2 dose of ATX-101, a measurable
reduction in SMF from baseline was observed as early as week 4 (p<0.05 vs.
placebo) and from week 12 onward, this dose was associated with
statistically significantly greater reductions in SMF compared with placebo based
on clinician assessment using CR-SMFRS (p<0.05 vs. placebo at weeks 16 and
32). Similarly, a statistically significantly greater reduction in SMF compared
with placebo was reported by subjects based on self-assessments using PR-SMFRS (p<0.05
vs. placebo measured at weeks 16 and 32). Subject assessments also demonstrated
a significant reduction in the self-evaluated overall visual and psychological
impact of SMF, including feeling happier, less bothered, less self-conscious,
less embarrassed, younger and less overweight following treatment with ATX-101 (p≤ 0.001 overall and for each
element vs. placebo at week 32). Clinician and patient-reported outcomes of SMF
reduction were confirmed by MRI assessments demonstrating a significant
reduction in SMF volume and thickness using a midline sagittal slice analysis
(p<0.01 vs. placebo at week 32). Across all measures, the 1 mg/cm2
dose was associated with a smaller reduction in SMF than the 2 mg/cm2 dose.
The most common adverse events with ATX-101, incidence >10%, were predominantly
mild to moderate, transient and included pain, numbness, bruising, edema/swelling,
redness, induration, pruritus, paresthesia and nodules. These were limited to
the injection site and largely resolved within the 28-day treatment interval. No drug-related systemic adverse events were observed with
ATX-101. Lipid profile and hepatic function were within normal range throughout
treatment.
Conclusion:
The 2 mg/cm2 ATX-101 dose was associated with significant improvements in clinician and patient-reported measures of SMF, and confirmed by objective evaluation using MRI. Additionally, ATX-101 treatment led to significant improvements in subjects' perceptions of the impact of their SMF. ATX-101 was well tolerated with no treatment-related systemic adverse events at the evaluated doses. The results from this Phase 2B trial suggest that ATX-101 may be a valuable pharmacologic approach for reducing SMF thereby improving patients' psychological and self-perception of appearance.
FIGURE: 32-year old male Phase 2B subject before (left, weight 81.8 kg) and after (right, weight 81.8 kg) treatment with ATX-101.