Histological Analysis of the Effect of ATX-101 (Deoxycholic Acid Injection) on Subcutaneous Fat: Results From a Phase 1 Open-Label Study.

ABSTRACT

BACKGROUND: ATX-101 is approved for submental fat reduction. OBJECTIVE: To characterize the histological effect of ATX-101 injection into subcutaneous fat. METHODS: This Phase 1 open-label study enrolled 14 adults to receive injections of ATX-101 into abdominal fat at varying concentrations (0.5%, 1.0%, 2.0%, or 4.0%), volumes (0.2 or 0.4 mL), spacing (0.7, 1.0, or 1.5 cm), and time points before scheduled abdominoplasty (1, 3, 7, or 28 days). During abdominoplasty, tissue was excised and preserved for histology. RESULTS: All injection paradigms resulted in histological changes confined to the subcutaneous layer, which were more prominent at higher concentrations and independent of volume and spacing. Key features at Day 1 after injection were adipocytolysis, blood vessel injury, neutrophilic inflammation, and lysis of locally present neutrophils. At Day 3, inflammation was reduced versus Day 1, and hemorrhage and lipid lake formation (at higher concentrations) were observed. Day 7 samples exhibited prominent adipocytolysis, mild inflammation, lipid-laden macrophages in the septae, and repair of vascular injury. At Day 28, inflammation was largely resolved and prominent features were septal thickening, neovascularization, and atrophy of fat lobules. CONCLUSION: Subcutaneous injection of ATX-101 induces adipocytolysis and local inflammation with septal thickening and resolution of inflammation by 28 days after injection.