Rocatinlimab: A Novel T-Cell Rebalancing Therapy Targeting the OX40 Receptor in Atopic Dermatitis

Atopic dermatitis (AD) is a chronic inflammatory disease characterized by eczematous skin lesions, intense pruritus, skin pain, sleep disruption, and mental health disturbances. There remains a need for a therapeutic option that delivers durable efficacy, safety, and convenient dosing across the AD patient population. This review provides an overview of AD pathogenesis driven by T-cell imbalance and describes a novel therapeutic option targeting the OX40 receptor, a costimulatory molecule expressed specifically on activated T cells. Expression of the OX40 receptor on skin-homing T cells is increased in AD. OX40-mediated activation of pathogenic T cells drives inflammation in AD and is critical for the formation of memory T cells, leading to persistent disease. Rocatinlimab (AMG 451/KHK4083) is a novel T-cell rebalancing therapy that inhibits and reduces pathogenic T cells by targeting the OX40 receptor. By reducing pathogenic T-cell number and activity, rocatinlimab has the potential to limit AD flares and modify the course of disease. Rocatinlimab showed promise for the treatment of moderate-to-severe AD in a phase 2b trial, significantly improving overall disease severity, skin involvement, pruritus, sleep disturbance, and quality of life compared with placebo at week 16. Improvements continued through week 36 during active treatment, and notably, were largely maintained in responders throughout a subsequent 20-week off-treatment period, providing evidence for durable on and off treatment responses. Rocatinlimab has also demonstrated a favorable safety and tolerability profile. A large, global phase 3 program (ROCKET) including eight studies is underway to further assess the efficacy, safety, maintenance of response, extended dosing, and off-treatment durability of rocatinlimab in adults and adolescents with moderate-to-severe AD.