pivekimab sunirine — Drug Monograph

Brand names: DECNUPAZ

Drug class: Antibody-Drug Conjugate

Mechanism of Action

Anti-CD123 (IL-3 receptor alpha chain) humanized monoclonal antibody conjugated to SG3249, a highly potent pyrrolobenzodiazepine (PBD) dimer payload, via a protease-cleavable linker. CD123 is markedly overexpressed on blastic plasmacytoid dendritic cell neoplasm (BPDCN) tumor cells and normal plasmacytoid dendritic cells. After internalization, SG3249 cross-links DNA in the minor groove causing irreversible double-strand DNA breaks and apoptosis in CD123-positive cells.

FDA Indications

Common Side Effects

Clinical Pearl

BPDCN is an exceptionally rare and aggressive hematologic malignancy (<1,000 cases/year in the US) with poor prognosis and historically no standard of care beyond tagraxofusp (SL-401, a CD123-directed cytotoxin fusion protein approved in 2018). Pivekimab-sunirine offers a true ADC-based approach targeting the same CD123 antigen. The PBD dimer payload class (shared with loncastuximab-tesirine) mandates vigilance for effusions and the same corticosteroid prophylaxis strategy. BPDCN commonly…

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