AstraZeneca (AZ, NASDAQ: AZN) has announced that it has received conditional market approval in China for its next-generation Bruton’s tyrosine kinase (BTK) inhibitor, Calquence (acalabrutinib). The drug is approved for the first indication in adults with mantle cell lymphoma (MCL) who have received at least one prior therapy.
Clinical Trial Support and Further Requirements
The approval is supported by data from two clinical trials, including the global Phase II ACE-LY-004 study and a China-based Phase I/II study. Further confirmatory trials will be required to convert this conditional approval to a full approval.
MCL and Calquence’s Efficacy
MCL is an aggressive but rare form of non-Hodgkin’s lymphoma (NHL), accounting for about 2%-6% of all NHL patients in China. In the ACE-LY-004 Phase II study, Calquence achieved an overall response rate (ORR) of 80.6% (95% confidence interval [CI] 72.6-87.2), with a complete response (CR) in 39.5% of patients with relapsed or refractory MCL (95% CI 30.9-48.7). Long-term follow-up data at 38.1 months showed that Calquence-treated patients remained progression-free for a median of 22 months, with a median overall survival (OS) of 59.2 months (95% CI 36.5-NE).
Development and Global Impact of Calquence
Calquence was originally discovered by US-Dutch firm Acerta Pharma and acquired by AZ in a USD 4 billion deal in 2016. As a second-generation BTK inhibitor, it offers improved selectivity and reduced toxicity compared to the first-in-class BTK inhibitor Imbruvica (ibrutinib), with fewer treatment discontinuations due to adverse events. Calquence was first approved in the US in 2017 for MCL, and for chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) in 2019. It has also received approvals in the EU, Japan, and other regions. AZ reported USD 2.05 billion in global sales of Calquence during 2022.
