OX40-OX40L Inhibition for the Treatment of Atopic Dermatitis-Focus on Rocatinlimab and Amlitelimab

Abstract

Despite the recent emergence of targeted therapeutic options, there are still unmet needs concerning moderate-to-severe atopic dermatitis treatment. This review aims to discuss the OX40-OX40L pathway as a therapeutic target for the treatment of atopic dermatitis. OX40 and OX40L are two checkpoint molecules that bind to potentiate pro-inflammatory T-cell responses that are pivotal to atopic dermatitis pathogenesis. Two OX40-OX40L inhibitors, rocatinlimab and amlitelimab, are being developed for the treatment of atopic dermatitis. Rocatinlimab, an anti-OX40 antibody, was evaluated in phase 2b, a randomized, placebo-controlled clinical trial. At week 16, rocatinlimab groups achieved a greater reduction in the EASI percentage change from the baseline (−48.3% to −61.1%) against the placebo (−15.0%; p < 0.001), and clinical response was maintained 20 weeks after the treatment had ceased. Amlitelimab, an anti-OX40L antibody, was studied in a 12-week treatment phase 2a clinical trial, with a significant efficacy response observed within 2 weeks. At week 16, amlitelimab groups reached the EASI mean percentage change from the baseline of −69.9% and −80.1% versus the placebo (−49.4%; p = 0.072 and p = 0.009). Among the responders, 68% of amlitelimab patients were sustained 24 weeks following the last dose. Both treatments were shown to be safe and well tolerated. Current evidence points to OX40-OX40L inhibitors as future options for atopic dermatitis treatment with potential disease-modifying effects.

Keywords: OX40; OX40-OX40L; amlitelimab; atopic dermatitis; rocatinlimab.

Figure 1

The co-stimulatory T-cell receptor OX40 is expressed predominantly on effector and regulatory T-cells. Its ligand, OX40L, is expressed on activated antigen-presenting cells and endothelial cells. Their interaction plays a central role in pro-inflammatory T-cell responses, including in atopic dermatitis. Rocatinlimab is a fully human anti-OX40 monoclonal antibody, which selectively depletes sOX40+ activated T-cells. On the other hand, amlitelimab, is a non-depleting IgG4 human anti-OX40L monoclonal antibody that binds OX40L and blocks interaction with OX40. Besides blocking antigens, the presenting T-cell activation, amlitelimab also blocks T-cell independent APC pro-inflammatory activity via the inhibition of OX40L back signaling.