Background: AN2728 topical ointment, 2% is a novel phosphodiesterase-4 inhibitor in development for treatment of atopic dermatitis (AD). This report summarizes findings from AN2728 phase 1b/2 AD studies.
Methods: Study 1 was a phase 1b, open-label, maximal-use trial designed to assess systemic exposure, safety, and efficacy (Investigator’s Static Global Assessment [ISGA] and AD signs/symptoms) in children and adolescents. Study 2 was a phase 2a, randomized, double-blind, bilateral trial designed to evaluate AN2728 efficacy (Atopic Dermatitis Severity Index [ADSI]) and safety in adults with 2 comparable target AD lesions. Study 3 was a phase 2a, open-label trial designed to evaluate safety, systemic exposure, and efficacy (ISGA and AD signs/symptoms) in adolescents. Study 4 was a phase 2, multicenter, randomized, double-blind study of the efficacy (ADSI based on AD signs/symptoms) and safety of once- or twice-daily treatment with AN2728 topical ointment 0.5% or 2% in adolescents. Â
Results: In study 1 (N=34), AN2728 was rapidly absorbed with limited systemic exposure; most treatment-emergent adverse events (TEAEs; 95%) were mild or moderate in intensity. Mean ISGA scores declined from baseline to day 29; improvement in pruritus severity was observed as early as day 5 (first assessment). In study 2 (N=25), 68% of patients experienced a greater decrease in ADSI score in AN2728-treated versus vehicle-treated lesions at day 28. Most TEAEs (90%) were mild. Limited AN2728 systemic exposure was demonstrated in study 3 (N=23); the most common TEAEs were application site pain and nasopharyngitis. Efficacy was demonstrated by reductions in mean ISGA and AD symptom severity scores. In study 4 (N=86), the greatest clinical improvements were observed with AN2728 topical ointment, 2% applied twice daily; 17 patients reported 20 TEAEs of mild (90%) or moderate (10%) severity.
Conclusion: Preliminary data suggests that AN2728 topical ointment, 2% may be safe and effective in patients with AD.