AbbVie announced the submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration for pivekimab sunirine (PVEK), an investigational antibody-drug conjugate targeting the rare blood cancer Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN). The regulatory filing represents a potential breakthrough for patients with this aggressive malignancy who face limited treatment options.
Clinical Development Foundation
The BLA submission is based on data from the Phase 1/2 CADENZA trial, a global multicenter, open-label study designed to determine the maximum tolerated dose, recommended Phase 2 dose, and optimal dosing schedule for PVEK monotherapy. The trial assessed safety, tolerability, pharmacokinetics, immunogenicity, and antileukemia activity of PVEK in subjects with CD123-positive hematologic malignancies, including BPDCN, acute myeloid leukemia (AML), and other blood cancers.
Addressing Critical Unmet Need
BPDCN is a rare and aggressive blood cancer that exhibits features of both leukemia and lymphoma. Patients typically present with skin lesions, and the disease often spreads to the bone marrow, central nervous system, and lymph nodes. Current first-line treatments consist of intensive chemotherapy, often followed by stem cell transplant, highlighting the significant need for additional and innovative treatment approaches for both newly diagnosed patients and those with relapsed or refractory disease.
"Meaningful innovations in cancer research and treatment are happening every day. It is important that these innovations reach patients who desperately need them, including those with rare cancers who have limited options," said Roopal Thakkar, executive vice president, research and development and chief scientific officer at AbbVie.
Targeted Therapeutic Approach
Pivekimab sunirine is a CD123-targeting antibody-drug conjugate designed to deliver potent cancer cell death-inducing agents directly to cancer cells expressing the CD123 protein. CD123 (IL-3Rα) is overexpressed in BPDCN, making it an ideal therapeutic target. This targeted approach represents AbbVie's first ADC in blood cancer development.
The investigational therapy is currently being evaluated as monotherapy for patients with BPDCN and in combination with Vidaza (azacitidine) and Venclexta (venetoclax) for patients with untreated and relapsed/refractory AML. The FDA granted PVEK Breakthrough Therapy designation in October 2020 for relapsed/refractory BPDCN, recognizing its potential to address a significant unmet medical need.
Regulatory Pathway Forward
The BLA submission marks a critical milestone in bringing this potential treatment to patients with BPDCN. Thakkar expressed optimism about the regulatory process, stating, "We look forward to next steps in the regulatory process for our latest Antibody-Drug Conjugate (ADC), our first ADC in blood cancer, and how it may advance treatment for those living with Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)."
The submission represents part of AbbVie's broader oncology strategy, which includes advancing a dynamic pipeline of investigational therapies across various cancer types through targeted treatment modalities including small molecule therapeutics, antibody-drug conjugates, immuno-oncology-based therapeutics, multispecific antibodies, and novel CAR-T platforms. The company is currently evaluating more than 35 investigational medicines in multiple clinical trials across widespread and debilitating cancers.
