Calquence Approved in EU for Chronic Lymphocytic Leukemia

AstraZeneca’s Calquence (acalabrutinib), a selective Bruton’s tyrosine kinase (BTK) inhibitor, has been approved in the European Union (EU) for the treatment of adult patients with chronic lymphocytic leukemia (CLL), the most common type of leukemia in adults.

The approval by the European Commission was based on positive results from two Phase III clinical trials, ELEVATE-TN in patients with previously untreated CLL and ASCEND in patients with relapsed or refractory CLL. This follows a recommendation for approval by the Committee for Medicinal Products for Human Use of the European Medicines Agency in July 2020.

“One of our biggest hurdles in treating chronic lymphocytic leukemia is finding tolerable treatment options that manage the disease long term, which typically impacts older patients with comorbidities. Today’s news marks great progress for patients in Europe, as the Phase III clinical trials for Calquence showed a significant improvement in comparison with current standard treatments,” Paolo Ghia, MD, Director, Strategic Research Program on CLL, Università Vita-Salute San Raffaele in Milan, and investigator of the ASCEND Phase III trial, said.

“This approval represents a key development for patients in Europe who until now have had limited chemotherapy-free treatment options. As our first European approval in blood cancers, Calquence provides a new tolerable treatment option with uncompromised efficacy and the potential to positively impact the quality of life for thousands of patients living with chronic lymphocytic leukemia,” Dave Fredrickson, Executive Vice President, Oncology Business Unit, said.

In the ELEVATE-TN Phase III trial, Calquence combined with obinutuzumab and as monotherapy reduced the risk of disease progression or death by 90% and 80%, respectively, compared with standard chemo-immunotherapy treatment chlorambucil plus obinutuzumab, in patients with previously untreated CLL. In the ASCEND Phase III trial, 88% of patients with relapsed or refractory CLL taking Calquence remained alive and free from disease progression after 12 months compared with 68% of patients on rituximab combined with idelalisib or bendamustine. Data from the interim results of the trials were published in The Lancet and Journal of Clinical Oncology, respectively.

Calquence is approved for the treatment of CLL and small lymphocytic lymphoma in the US and is approved for CLL in several other countries worldwide. Calquence is also approved for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy in the US and several other countries. Calquence is not currently approved for the treatment of MCL in Europe.

As part of a broad development program, Calquence is being assessed in more than 20 AstraZeneca-sponsored clinical trials for the treatment of patients with B-cell malignancies including CLL, MCL, diffuse large B-cell lymphoma (DLBCL), Waldenström’s macroglobulinaemia (WM), follicular lymphoma (FL), and other hematologic malignancies.

Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in adults, with an estimated 105,000 new cases globally in 2016, and the number of people living with CLL is expected to grow with improved treatment as patients live longer with the disease. In CLL, too many blood stem cells in the bone marrow become abnormal lymphocytes and these abnormal cells have difficulty fighting infections. As the number of abnormal cells grows there is less room for healthy white blood cells, red blood cells, and platelets. This could result in anemia, infection, and bleeding. B-cell receptor signaling through BTK is one of the essential growth pathways for CLL.