Bispecific and trispecific antibodies in atopic dermatitis: a review of the emerging clinical pipeline

Biologic therapies have reshaped treatment of atopic dermatitis, yet most available agents target only one cytokine or receptor and many patients still do not reach minimal disease activity. Data from real-world practice shows that most individuals treated with current monospecific biologics fail to achieve Eczema Area and Severity Index 90 (EASI 90), clear or almost clear global assessments, or itch scores of 0 or 1. Janus kinase inhibitors reach higher clearance and itch targets because they concurrently block multiple cytokine pathways, exposing an efficacy gap and prompting development of multi-specific biologics. This review links atopic dermatitis endotypes and neuroimmune itch pathways to emerging multi-target designs and provides a focused overview of the growing pipeline of bispecific and trispecific antibodies, nanobody constructs, and antibody cocktails. Agents discussed include NM26-2198 (JNJ-5939), PX128, PX130, ZL-1503, BBT001, ATTO-002, PF-07264660, PF-07275315, GB12-09, APG279 (APG777+APG990), Galvokimig (UCB9741), Donzakimig (UCB1381), TRIV-509, TRIV-573, SAR443765 (Lunsekimig), CM512, ATI-052, and ZW1572. Early clinical data suggest the potential for faster improvement, reliable itch control, and longer dosing intervals. This review highlights the potential for shifting treatment options in atopic dermatitis.