Acalabrutinib

Acalabrutinib (trade name Calquence) is a medication used to treat a type of non-Hodgkin lymphoma known as mantle cell lymphoma.[2] Specifically it is for people who had previously been treated with another therapy.[3] As of 2019, it was unclear whether it improved outcomes.[2]

Acalabrutinib
Clinical data
Trade namesCalquence
Other namesACP-196
AHFS/Drugs.comMonograph
License data
Pregnancy
category
  • AU: C [1]
  • US: N (Not classified yet) [1]
    Routes of
    administration    		By mouth
    ATC code
    Legal status
    Legal status
    Identifiers
    CAS Number
    PubChem CID
    DrugBank
    ChemSpider
    UNII
    KEGG
    ChEMBL
    ECHA InfoCard100.247.121
    Chemical and physical data
    FormulaC26H23N7O2
    Molar mass465.517 g·mol−1
    3D model (JSmol)

    Common side effects include headaches, feeling tired, low red blood cells, low platelets, and low white blood cells.[2] It is a second generation Bruton's tyrosine kinase inhibitor.[4][5]

    Acalabrutinib was approved for medical use in the United States in 2017.[2] The wholesale cost as of 2018 in the United States is US$14,064 per month.[6]

    Medical uses

    It is used to treat a type of non-Hodgkin lymphoma known as mantle cell lymphoma.[2] It is unclear if it results in improved outcomes as of 2019.[2]

    Side effects

    The most common adverse events were headache, diarrhea and weight gain.[5] Despite the appearance of a greater occurrence of transient headaches, data suggest a preferred advantage of acalabrutinib over ibrutinib due to expected reduced adverse events of skin rash, severe diarrhea, and bleeding risk.[5]

    Society and culture

    Names

    Acalabrutinib is the INN.[7]

    Regulatory

    As of February 2016, acalabrutinib had received orphan drug designation in the United States for mantle cell lymphoma and chronic lymphocytic leukemia (CLL),[8] [9] 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 - CLL/ small lymphocytic lymphoma (SLL), mantle cell lymphoma (MCL), and lymphoplasmacytic lymphoma (Waldenström's macroglobulinaemia, WM).[10][11][12][13] Approval would result in a 10-year period of market exclusivity for the stated indications within Europe.[14]

    Economics

    It was developed by Acerta Pharma.[15] After promising results for CLL in initial clinical trials,[4] 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 approval in both the US and Europe and the establishment of commercial opportunity.[16]

    Research

    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.[5] 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.[5] These findings strongly suggest an improved safety profile of acalabrutinib with minimized adverse effects relative to ibrutinib.[5] In pre-clinical studies, it was shown to be more potent and selective than ibrutinib, the first-in-class BTK inhibitor.[4][5][17]

    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.[4] 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.[5]

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    References
    1. "Acalabrutinib (Calquence) Use During Pregnancy". Drugs.com. 23 October 2019. Retrieved 28 March 2020.
    2. "Acalabrutinib Monograph for Professionals". Drugs.com. Retrieved 16 March 2019.
    3. "FDA approves new treatment for adults with mantle cell lymphoma". U.S. Food and Drug Administration (FDA) (Press release). 31 October 2017. Retrieved 28 March 2020.
    4. Byrd JC, Harrington B, O'Brien S, Jones JA, Schuh A, Devereux S, et al. (January 2016). "Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia". The New England Journal of Medicine. 374 (4): 323–32. doi:10.1056/NEJMoa1509981. PMC 4862586. PMID 26641137.
    5. Wu J, Zhang M, Liu D (March 2016). "Acalabrutinib (ACP-196): a selective second-generation BTK inhibitor". Journal of Hematology & Oncology. 9: 21. doi:10.1186/s13045-016-0250-9. PMC 4784459. PMID 26957112.
    6. "In Brief: Acalabrutinib (Calquence) for Mantle Cell Lymphoma (online only)". The Medical Letter. Retrieved 16 March 2019.
    7. "WHO Drug Information - recommended INN" (PDF). WHO Drug Information. World Health Oorganisation. Retrieved 24 December 2015.
    8. "Acalabrutinib Orphan Drug Designation and Approval". U.S. Food and Drug Administration (FDA). Retrieved 15 April 2020.
    9. "Acalabrutinib Orphan Drug Designation and Approval". U.S. Food and Drug Administration (FDA). Retrieved 15 April 2020.
    10. "EU/3/16/1624". European Medicines Agency (EMA). 2 May 2016. Retrieved 15 April 2020.
    11. "EU/3/16/1625". European Medicines Agency (EMA). 4 May 2016. Retrieved 15 April 2020.
    12. "EU/3/16/1626". European Medicines Agency (EMA). 4 May 2016. Retrieved 15 April 2020.
    13. "azn201602256k.htm". www.sec.gov. Retrieved 2016-11-21.
    14. House DW (2016-02-25). "AstraZeneca and Acerta Pharma's acalabrutinib tagged an Orphan Drug in Europe for three indications". Seeking Alpha. Retrieved 2016-11-21.
    15. "AstraZeneca to buy Acerta for blood cancer drug". www.rsc.org. Chemistry World - Royal Society of Chemistry. Retrieved 24 December 2015.
    16. Walker I, Roland D (2015-12-17). "AstraZeneca to Buy Stake in Acerta Pharma". Wall Street Journal. ISSN 0099-9660. Retrieved 2016-11-19.
    17. Wu J, Zhang M, Liu D (March 2016). "Acalabrutinib (ACP-196): a selective second-generation BTK inhibitor". Journal of Hematology & Oncology. 9 (1): 21. doi:10.1186/s13045-016-0250-9. PMC 4784459. PMID 26957112.
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