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Acalabrutinib, sold under the brand name Calquence, is a medication used to treat various types of
non-Hodgkin lymphoma Non-Hodgkin lymphoma (NHL), also known as non-Hodgkin's lymphoma, is a group of blood cancers that includes all types of lymphomas except Hodgkin lymphomas. Symptoms include enlarged lymph nodes, fever, night sweats, weight loss, and tirednes ...
, including
mantle cell lymphoma Mantle cell lymphoma (MCL) is a type of non-Hodgkin's lymphoma (NHL), comprising about 6% of NHL cases. There are only about 15,000 patients presently in the United States with mantle cell lymphoma. It is named for the mantle zone of the lymph n ...
(MCL) and chronic lymphocytic leukemia/small lymphocytic leukemia (CLL/SLL). It may be used both in relapsed as well as in treatment-naive settings. Common side effects include headaches, feeling tired, low red blood cells,
low platelets Thrombocytopenia is a condition characterized by abnormally low levels of platelets, also known as thrombocytes, in the blood. It is the most common coagulation disorder among intensive care patients and is seen in a fifth of medical patients an ...
, and low white blood cells. It is a second generation Bruton's tyrosine kinase inhibitor. Acalabrutinib blocks an enzyme called Bruton's tyrosine kinase, which helps B cells to survive and grow. By blocking this enzyme, acalabrutinib is expected to slow down the build-up of cancerous B cells in CLL, thereby delaying progression of the cancer. Acalabrutinib was approved for medical use in the United States in 2017, and in the European Union in November 2020. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.


Medical uses

In the European Union, acalabrutinib as monotherapy or in combination with
obinutuzumab Obinutuzumab, sold under the brand name Gazyva among others, is a humanized anti-CD20 monoclonal antibody, originated by GlycArt Biotechnology AG and developed by Roche as a cancer treatment. It can be used as a first-line treatment for chronic ly ...
is
indicated In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ...
for the treatment of adults with previously untreated chronic lymphocytic leukaemia (CLL). It is also indicated for the treatment of adults with chronic lymphocytic leukaemia (CLL) who have received at least one prior therapy. In the United States, acalabrutinib is indicated for the treatment of adults with mantle cell lymphoma (MCL) who have received at least one prior therapy, and for the treatment of adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).


Side effects

The most common adverse events were headache, diarrhea and weight gain. 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.


Society and culture


Legal status

Acalabrutinib was approved for medical use in the United States in 2017, and in the European Union in November 2020. As of February 2016, acalabrutinib had received orphan drug designation in the United States for
mantle cell lymphoma Mantle cell lymphoma (MCL) is a type of non-Hodgkin's lymphoma (NHL), comprising about 6% of NHL cases. There are only about 15,000 patients presently in the United States with mantle cell lymphoma. It is named for the mantle zone of the lymph n ...
and chronic lymphocytic leukemia (CLL), 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 Chronic lymphocytic leukemia (CLL) is a type of cancer in which the bone marrow makes too many lymphocytes (a type of white blood cell). Early on, there are typically no symptoms. Later, non-painful lymph node swelling, feeling tired, fever ...
(SLL), mantle cell lymphoma (MCL), and lymphoplasmacytic lymphoma ( Waldenström's macroglobulinaemia, WM). Approval would result in a 10-year period of market exclusivity for the stated indications within Europe.


Economics

It was developed by Acerta Pharma. After promising results for CLL in initial clinical trials,
Astra Zeneca AstraZeneca plc () is a British-Swedish multinational pharmaceutical and biotechnology company with its headquarters at the Cambridge Biomedical Campus in Cambridge, England. It has a portfolio of products for major diseases in areas includin ...
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.


Names

Acalabrutinib is the international nonproprietary name (INN), and the
United States Adopted Name A United States Adopted Name (USAN) is a unique nonproprietary name assigned to a medication marketed in the United States. Each name is assigned by the USAN Council, which is co-sponsored by the American Medical Association (AMA), the United Sta ...
(USAN).


Research

Relative to
ibrutinib Ibrutinib, sold under the brand name Imbruvica among others, is a small molecule drug that inhibits B-cell proliferation and survival by irreversibly binding the protein Bruton's tyrosine kinase (BTK). Blocking BTK inhibits the B-cell receptor ...
, 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 Ibrutinib, sold under the brand name Imbruvica among others, is a small molecule drug that inhibits B-cell proliferation and survival by irreversibly binding the protein Bruton's tyrosine kinase (BTK). Blocking BTK inhibits the B-cell receptor ...
, the first-in-class BTK inhibitor. The interim results of the still on-going first human phase I/II 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.


References


External links

* * * {{Portal bar , Medicine Antineoplastic drugs Human proteins Tyrosine kinase inhibitors AstraZeneca brands Alkyne derivatives Orphan drugs