Topical Ocular Anti-TNFα Agent Licaminlimab in the Treatment of Acute Anterior Uveitis: A Randomized Phase II Pilot Study

Abstract

Purpose: Licaminlimab is a new anti-TNFα antibody fragment for topical ocular application. This phase II study assessed the tolerability, treatment effect, and pharmacokinetics of licaminlimab in acute anterior uveitis (AAU). Methods: In this multicenter, randomized, parallel-group, double-masked study, 43 adult patients with non-infectious AAU and Standardization of Uveitis Nomenclature (SUN) anterior chamber (AC) cell score of 2+ or 3+ were randomized (3:1 ratio) to licaminlimab (60 mg/mL, 8 drops/day for 15 days, 4 drops/day for 7 days, then matching vehicle for 7 days) or dexamethasone eye drops (8 drops/day for 15 days, tapering to 1 drop/day over 14 days). The primary efficacy end point was clinical response (≥2-step decrease in AC cell grade at day 15). A treatment effect was considered as established if the lower limit of the 95% posterior interval of the responder rate was >30%. Serum levels of licaminlimab were determined. Results: The day 15 response rate for licaminlimab was 56%; the lower bound of the 95% credible interval was 40% (i.e. >30%), demonstrating a treatment effect according to prespecified criteria. By day 4, 36% of licaminlimab-treated patients were responders; 76% had an AC cell grade of 0 on ≥1 post-treatment visit. The day 15 dexamethasone response rate was 90% (no inferential between-arm comparison was planned). Both treatments were well-tolerated. Intraocular pressure increased from baseline with dexamethasone but not licaminlimab. Licaminlimab was undetectable in serum in most patients. Conclusions: Licaminlimab is the first biologic demonstrated to have a treatment effect on an intraocular condition with topical ocular application. The trial met its primary objective and the observed responder rate for licaminlimab was 56.0%. Ocular administration of licaminlimab was well-tolerated in adult subjects with AAU for up to 35 days.