AstraZeneca's BTK Inhibitor Calquence Receives FDA Approval for Adult Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma

On November 25, 2019, VCBeat (WeChat ID: vcbeat) learned from foreign media reports that AstraZeneca announced its BTK inhibitor Calquence (acalabrutinib) had received FDA approval as both an initial and subsequent therapy for the treatment of adult chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Under another FDA pilot program, Orbis, the Australian Therapeutic Goods Administration (TGA) and Health Canada also approved Calquence for the treatment of CLL.

CLL and SLL are the most common types of leukemia in adults and are blood cancers that affect lymphocytes, with approximately 200,000 new cases globally each year. In CLL patients, cancer cells are primarily located in the blood and bone marrow, whereas in SLL patients, they are mainly found in the lymph nodes. Patients with these two diseases predominantly present with anemia, thrombocytopenia, fatigue, and lymphadenopathy, and face a higher risk of complications.

Calquence is a Bruton's tyrosine kinase (BTK) inhibitor developed by AstraZeneca. It binds covalently to BTK, thereby inhibiting its activity. BTK is a key kinase in the B-cell antigen receptor (BCR) signaling pathway. This enzyme primarily affects B cells and represents an important therapeutic target for autoimmune diseases and B-cell-related malignancies. Preclinical studies have demonstrated that Calquence exhibits higher affinity and specificity compared to ibrutinib, another BTK-targeted inhibitor.

This approval is based on the results of two randomized, active-controlled Phase III clinical trials. The first trial enrolled a total of 535 treatment-naïve patients with chronic lymphocytic leukemia (CLL), and the second trial enrolled a total of 310 previously treated patients with CLL. Results from both trials demonstrated that Calquence, both as monotherapy and in combination regimens, significantly prolonged progression-free survival (PFS) compared with standard therapy.

As early as 2017, Calquence received FDA approval for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL). Previously, the FDA had granted Calquence Breakthrough Therapy Designation and Priority Review for the treatment of chronic lymphocytic leukemia (CLL). Currently, AstraZeneca is exploring the efficacy of Calquence in other hematologic malignancies.

Currently, the indications for Calquence include various B-cell-related hematologic malignancies, such as chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma, Waldenström macroglobulinemia (WM), follicular lymphoma (FL), multiple myeloma, and other hematologic cancers. AstraZeneca has high commercial expectations for Calquence, with its peak sales projected to reach $5 billion.

AstraZeneca (NYSE: AZN), founded in 1999 and headquartered in London, UK, is an innovation-driven global biopharmaceutical company. The company is primarily engaged in the research, development, manufacturing, and marketing of prescription medicines, committed to improving the quality of life for patients worldwide.

Richard Pazdur, M.D., Director of the Office of Oncologic Diseases at the U.S. FDA, stated, “We conducted the multinational collaborative Orbis Pilot Project for Calquence, and based on the results of this project, obtained FDA approval, making this drug a new treatment option for adult patients with CLL and SLL. Moving forward, we will continue to explore other indications for Calquence.”

(Compiled by Xu Xiaoxue)