Safety, pharmacokinetics, and efficacy of HY-072808 ointment, a novel PDE4 inhibitor, in adolescent and adult patients with mild-to-moderate AD

HY-072808 is a new PDE4 inhibitor with potential anti- atopic dermatitis (AD) effects. This study aimed to investigate its safety and pharmacokinetics in healthy individuals, and subsequently, its safety, pharmacokinetics, and efficacy in patients with mild-to-moderate AD. We conducted double-blind, placebo-controlled, single and multiple ascending dose phase I clinical trials to assess the safety and pharmacokinetics of HY-072808 ointment in healthy subjects, followed by an open-label trial to evaluate its safety, pharmacokinetics, and efficacy in adolescent and adult patients with mild-to-moderate AD. The trials included 73 healthy subjects and 20 patients with AD. We found that HY-072808 had a favorable safety profile, with mild and manageable adverse events reported in both healthy subjects and AD patients. The pharmacokinetic analysis revealed that systemic exposure to HY-072808 remained minimal, with drug concentrations staying in the nanogram range. Furthermore, significant improvements in eczema severity, pruritus, and quality of life were observed in patients with mild-to-moderate AD, with 57.9% of patients achieving a ≥ 75% reduction in the EASI score. These results indicate the potential of HY-072808 as an effective and well-tolerated treatment for mild-to-moderate AD, suggesting further clinical development for use in both adolescent and adult patients. Chinese Clinical Trial Registry (No. ChiCTR2400087123).