|Chemical and physical data|
|Molar mass||465.517 g·mol−1|
|3D model (JSmol)|
Acalabrutinib (trade name Calquence) is a medication used to treat a type of non-Hodgkin lymphoma known as mantle cell lymphoma. Specifically it is for people who had previously been treated with another therapy. It is unclear if it results in improved outcomes as of 2019.
The most common adverse events were headache, diarrhea and weight gain. Despite the appearance of a greater occurrence of transient headaches, data suggests a preferred advantage of acalabrutinib over ibrutinib due to expected reduced adverse events of skin rash, severe diarrhea, and bleeding risk.
Society and culture
As of February 2016, acalabrutinib had received orphan designation in the United States for CLL only, and was similarly designated as an orphan medicinal product by the European Medicines Agency (EMA) Committee for Orphan Medicinal Products (COMP) for treatment of three indications - chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL), mantle cell lymphoma (MCL), and lymphoplasmacytic lymphoma (Waldenström's macroglobulinaemia, WM). If the drug is ultimately approved, this designation will result in a 10-year period of market exclusivity for the stated indications within Europe.
It was developed by Acerta Pharma. After the promising results for the treatment of CLL in initial clinical trials, Astra Zeneca purchased a 55% stake in Acerta Pharma for $4 billion in December 2015, with an option to acquire the remaining 45% stake for an additional $3 billion, conditional on the first approval in both the US and Europe and the establishment of commercial opportunity.
Relative to ibrutinib, acalabrutinib demonstrated higher selectivity and inhibition of the targeted activity of BTK, while having a much greater IC50 or otherwise virtually no inhibition on the kinase activities of ITK, EGFR, ERBB2, ERBB4, JAK3, BLK, FGR, FYN, HCK, LCK, LYN, SRC, and YES1. In addition, in platelets treated with ibrutinib, thrombus formation was clearly inhibited while no impact to thrombus formation was identified relative to controls for those treated with acalabrutinib. These findings strongly suggest an improved safety profile of acalabrutinib with minimized adverse effects relative to ibrutinib. In pre-clinical studies, it was shown to be more potent and selective than ibrutinib, the first-in-class BTK inhibitor.
The interim results of the still on-going first human phase 1/2 clinical trial (NCT02029443) with 61 patients for the treatment of relapsed chronic lymphocytic leukemia (CLL) are encouraging, with a 95% overall response rate demonstrating potential to become a best-in-class treatment for CLL. Notably, a 100% response rate was achieved for those people which were positive for the 17p13.1 gene deletion - a subgroup that typically results in a poor response to therapy and expected outcomes.
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- Wu, Jingjing; Zhang, Mingzhi; Liu, Delong (2016-03-09). "Acalabrutinib (ACP-196): a selective second-generation BTK inhibitor". Journal of Hematology & Oncology. 9 (1). doi:10.1186/s13045-016-0250-9. ISSN 1756-8722. PMC 4784459. PMID 26957112.