FDA approves AbbVie’s DECNUPAZ (pivekimab sunirine-pvzy), the first CD123-targeting antibody-drug conjugate for blastic plasmacytoid dendritic cell neoplasm (BPDCN), supported by Phase 1/2 CADENZA trial results.
Written By: Samiksha Jadhav, BPharm
Reviewed By: Pharmacally Editorial Team
FDA approved AbbVie’s DECNUPAZ (pivekimab sunirine-pvzy) for adults with blastic plasmacytoid dendritic cell neoplasm (BPDCN), a rare and aggressive hematologic malignancy. The approval establishes DECNUPAZ as the first FDA-cleared CD123-targeting antibody-drug conjugate (ADC) for BPDCN and addresses a significant unmet need in hematologic oncology.
Disease Context
BPDCN is a rapidly progressing blood cancer that often presents with skin lesions before spreading to the bone marrow, lymph nodes, and central nervous system. The disease primarily affects older adults and carries a high relapse risk despite intensive chemotherapy and stem cell transplantation.
Clinical Evidence
Approval was supported by the global Phase 1/2 CADENZA trial.
- In newly diagnosed BPDCN without CNS involvement (n=33), DECNUPAZ produced a 69.7% composite complete response rate with a median duration of response of 9.7 months. Thirteen patients (39.4%) proceeded to stem cell transplantation.
- In relapsed or refractory BPDCN (n=51), the ADC achieved a 15.7% composite complete response rate with responses lasting a median of 9.2 months. Six patients subsequently underwent stem cell transplantation.
Safety Profile
Safety findings aligned with the established toxicity profile of ADC therapies. The most common adverse events included edema, fatigue, musculoskeletal pain, hemorrhage, infusion-related reactions, nausea, and diarrhea.
DECNUPAZ carries a boxed warning for hepatotoxicity, including hepatic veno-occlusive disease, alongside warnings for infusion-related reactions, edema, sulfite allergic reactions, and embryo-fetal toxicity.
Mechanism of Action
DECNUPAZ targets CD123, a protein highly expressed on BPDCN cells. The ADC delivers an indolinobenzodiazepine pseudodimer payload that induces DNA damage and apoptosis. AbbVie noted that the therapy can be initiated in the outpatient setting, offering a practical option for patients with advanced disease.
Expert Opinion
Roopal Thakkar, M.D., executive vice president, research and development and chief scientific officer at AbbVie, emphasized the company’s continued focus on advancing therapies for difficult-to-treat cancers.
Naveen Pemmaraju, M.D., professor of leukemia at The University of Texas MD Anderson Cancer Center, highlighted the importance of a new outpatient treatment option for patients with relapsed or refractory disease.
About the CADENZA Trial
The CADENZA trial (NCT03386513) is a Phase 1/2, multicenter, open-label study evaluating pivekimab sunirine-pvzy in CD123-positive hematologic malignancies, including BPDCN. Results published in the Journal of Clinical Oncology included 84 patients: 33 newly diagnosed without CNS involvement and 51 with relapsed or refractory disease. Eleven frontline patients had additional cancer diagnoses, highlighting the complexity of treatment in this group.
Regulatory Pathway and Outlook
Pivekimab sunirine-pvzy received Breakthrough Therapy Designation in 2020 for relapsed or refractory BPDCN. AbbVie plans to continue evaluating DECNUPAZ across additional CD123-positive hematologic malignancies and broader treatment settings.
References
About the Writer
Samiksha Vikram Jadhav (LinkedIn) is a B. Pharm graduate with a strong academic foundation in pharmaceutical sciences, pharmacology, and drug development. She specializes in pharma market research, with a focused interest in mergers and acquisitions, strategic partnerships, and global pharma and biotech deals. Her work centers on analyzing industry transactions, market positioning, and business strategies, translating complex developments into clear, accurate, and insightful scientific and commercial reporting.