AstraZeneca's BTK Inhibitor Calquence Approved in Japan for Relapsed or Refractory Chronic Lymphocytic Leukemia, Offering a Chemotherapy-Free Option

January 27, 2021/BioValleyBIOON/--AstraZeneca(AstraZeneca) recently announced that the Japanese Ministry of Health, Labour and Welfare (MHLW) has approved the targeted anticancer drug Calquence (acalabrutinib), a next-generation selective Bruton’s tyrosine kinase (BTK) inhibitor, for the treatment of relapsed or refractory chronic lymphocyticLeukemia(CLL, including small lymphocytic lymphoma [SLL]) adult patients.

Globally, chronic lymphocytic leukemia (CLL) is the most common type of leukemia in adults; however, in Japan and East Asia, it is considered a rare disease, accounting for 1%–2% of all diagnosed leukemia cases.

This approval is based on data from the Phase III ASCEND trial and a Phase I trial conducted in Japanese patients. The results demonstrated that monotherapy with Calquence achieved statistically significant and clinically meaningful improvements in progression-free survival (PFS) compared with physician-selected standard-of-care regimens, either IdR (rituximab plus idelalisib) or BR (rituximab plus bendamustine), in patients with relapsed or refractory chronic lymphocytic leukemia (CLL).

In the ASCEND study,Compared with the IdR or BR regimen, Calquence significantly reduced the risk of disease progression or death by 69%.At month 12, 88% of patients in the Calquence treatment group were progression-free, compared with 68% in the control group. After a median follow-up of 16.1 months, the median PFS had not been reached in the Calquence monotherapy group, whereas it was 16.5 months in the control group.

The safety and tolerability profile of Calquence is consistent with the established profile. The final results of the Phase III ASCEND trial were presented at the 2020 American Society of Clinical Oncology (ASCO)TumorAmerican Society of Clinical Oncology (ASCO) and the 2020 European Hematology Association (EHA) OnlineMeetingpublished, demonstrating the long-term efficacy (median follow-up of 22 months) and tolerability of Calquence in the treatment of CLL.

AstraZenecaTumorDave Fredrickson, Executive Vice President of the Business Unit, stated: “Although the incidence of chronic lymphocytic leukemia (CLL) in Japan is lower than in other regions, patients still require innovative treatment regimens. The approval of Calquence provides a new, chemotherapy-free, and well-tolerated treatment option for patients in Japan, offering unparalleled efficacy and the potential to positively impact quality of life.”

The active pharmaceutical ingredient of Calquence is acalabrutinib, a highly selective, potent, covalent Bruton's tyrosine kinase (BTK) inhibitor that acts by irreversibly binding to and inhibiting BTK. BTK is a key regulator of the B-cell receptor (BCR) signaling pathway and is widely expressed in various types of hematologic malignancies, where it plays a role in B-cell proliferation, trafficking, chemotaxis, and adhesion, making it a therapeutic target for hematologic malignanciesTumorimportant target. In preclinical studies, acalabrutinib demonstrated minimal off-target effects.

Calquence was approved in the United States in October 2017FDAAccelerated approval for marketing was granted, with indications including: (1) adult patients with relapsed or refractory mantle cell lymphoma (MCL) who have previously received at least one prior therapy; and (2) adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). In November 2020, Calquence received European Union approval for first-line and subsequent-line treatment of CLL. In the European Union and Japan, Calquence has not yet been approved for the treatment of MCL.

Currently, Calquence is being developed for the treatment of various B-cell hematologic cancers, including chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), Waldenström macroglobulinemia (WM), follicular lymphoma (FL), multiple myeloma, and other hematologic malignancies.Tumor。

Calquence shares the same mechanism of action as AbbVie/J&J’s blockbuster hematologic malignancy drug Imbruvica (ibrutinib), the first BTK inhibitor approved globally. Since its initial approval in November 2013, Imbruvica has received approval for up to 11 therapeutic indications across six disease areas, with global sales rising sharply. In late June this year, the pharmaceutical market research firm EvaluatePharma released a report predicting that, driven by continuous market penetration and an expanding number of indications, Imbruvica’s sales will reach $10.722 billion in 2026, making it the fifth best-selling drug worldwide. (Bioon.com)

Original Source: Calquenceapproved in Japan for the treatment of relapsed or refractory chronic lymphocytic leukaemia