AbbVie (NYSE: ABBV) has received US FDA approval for Decnupaz (pivekimab sunirine-pvzy), an antibody-drug conjugate (ADC) targeting CD123, for the treatment of adult patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN). The approval marks the first ADC cleared by the FDA for this ultra-rare hematologic malignancy and represents AbbVie’s first ADC approval in blood cancer. It also marks the first molecule to emerge with approval from AbbVie’s 2023 USD 10.1 billion acquisition of ImmunoGen, which originally discovered and developed pivekimab sunirine.

Decnupaz is approved broadly for adult patients with BPDCN, without restriction by line of therapy. A notable feature of the approval is that treatment can be initiated in an outpatient setting, distinguishing it from more intensive inpatient regimens historically used in this disease. The drug carries a boxed warning for hepatotoxicity, including hepatic veno-occlusive disease, which can be severe or fatal. Additional warnings cover infusion-related reactions, edema, sulfite allergic reactions, and embryo-fetal toxicity.

The approval is supported by data from the Phase I/II CADENZA trial (NCT03386513), a multicenter, open-label study evaluating pivekimab sunirine-pvzy in patients with CD123-positive hematologic malignancies, including both newly diagnosed and relapsed or refractory BPDCN. Results were published in the Journal of Clinical Oncology. Among 33 newly diagnosed patients without central nervous system involvement, the composite complete response rate was 69.7%, with a median duration of response of 9.7 months; 13 patients (39.4%) subsequently received stem cell transplant. In the relapsed or refractory cohort of 51 patients, the composite complete response rate was 15.7%, with a median duration of response of 9.2 months, and 6 patients (11.8%) proceeded to transplant. The most common adverse reactions occurring in 20% or more of patients included edema, fatigue, musculoskeletal pain, hemorrhage, infusion-related reactions, nausea, and diarrhea.

Competitive context

Decnupaz delivers its cytotoxic effect through CD123-directed antibody-drug conjugate biology. CD123, the alpha subunit of the interleukin-3 receptor, is overexpressed on BPDCN cells, providing a cell-surface target for selective drug delivery. Upon binding and internalization, the conjugated payload — an indolinobenzodiazepine pseudodimer — alkylates DNA and induces single-strand breaks without crosslinking, triggering apoptosis. This mechanism differs from the protein synthesis inhibition employed by the only other approved BPDCN-specific therapy, tagraxofusp-erzs (Elzonris), which uses a CD123-directed IL-3 diphtheria toxin fusion protein. Developed by Stemline Therapeutics and now part of the Menarini Group, tagraxofusp received FDA approval in December 2018 as the first therapy approved specifically for BPDCN. Decnupaz’s outpatient initiation profile and ADC modality add a differentiated option to a therapeutic landscape that, until now, comprised a single approved agent alongside off-label chemotherapy regimens.

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