Acalabrutinib vs ibrutinib, what the differences are between them?

Before talking about the topic of “acalabrutinib vs ibrutinib”, we want to simply introduce the basic information about acalabrutinib and ibrutinib. Acalabrutinib is a targeted therapeutic agent that restrains the function of Bruton's tyrosine kinase (BTK). BTK is an intracellular protein that may exist in the overexpressed phenomenon in malignant B cells. Acalabrutinib is a BTK inhibitor that can block the signal of BCR and inhibit the growth and survival of malignant B-cell tumors.

Ibrutinib is the second new drug that has been approved through the FDA's Breakthrough Drug Way (the first being approved is obinutuzumab). Ibrutinib possesses two additional FDA buffs and enjoys administrative protection for seven years after it comes into the market. This medicine can be used to treat mantle cell lymphoma (MCL) and it was approved by the U.S. Food and Drug Administration in 2013.

Acalabrutinib vs ibrutinib, let’s find out the differences!

Research presented in 2021 showed that acalabrutinib was no less effective than ibrutinib and was better tolerated in the treatment of patients with chronic lymphocytic leukemia (CLL) with del (17p) or del (11q) who had previously been treated.

The Bruton tyrosine kinase (short for BTK) inhibitor is an effective drug to treat B-cell malignancies. Ibrutinib, the first BTK inhibitor, has been approved in more than 80 countries all over the world. Acalabrutinib is a second-generation BTK inhibitor, which works by blocking the action of abnormal proteins that signal cancer cells to multiply, which is very helpful to stop them from spreading.

Other endpoints were similar between the two therapies: the incidence of grade 3 was 30.8% and 30.0% in the acalabrutinib and ibrutinib groups, respectively. The incidence of Richter conversion was 3.8% and 4.9% respectively. Average overall survival was not obtained in both groups. There were 63 (23.5%) deaths in the acalabrutinib group and 73 (27.5%) deaths in the ibrutinib group.

The incidence of adverse events (≥20%) in all grades was lower in the acalabrutinib group than in the ibrutinib group: hypertension (9.4% and 23.2%, respectively), and diarrhea (34.3% and 46.0%, respectively). However, the incidence of some adverse events was higher in the acalabrutinib group than in the ibrutinib group, such as headache (34.6% and 20.2%, respectively). 

The resistance of ibrutinib is not common but increasing, and more studies have paid attention to assessing the risk of resistance in patients who should be healed with combination therapy. So now acalabrutinib can be chosen to treat complex diseases, which is superior to ibrutinib in terms of tolerance.

The researchers discovered that acalabrutinib is a more selective inhibitor of Bruton's tyrosine kinase (BTK). Acalabrutinib and ibrutinib work through irreversibly binding to and destroying cancerous B lymphocytes. The increased selectivity of acalabrutinib means that the risk of off-target cells or non-cancer cells is much lower than that of ibrutinib, thus reducing the risk of adverse reactions. "These results show that acalabrutinib has the same effect as ibrutinib in previously treated CLL patients, but is better tolerated and safer," said Dr. Byrd.

Mechanism of action: acalabrutinib vs ibrutinib

Besides the above differences between acalabrutinib vs ibrutinib, we still want to introduce the differences between them from the action mechanism.

Acalabrutinib, as a new B-cell inhibitor, is very effective in treating chronic lymphocytic leukemia and small lymphocytic lymphoma by selectively inhibiting BTK and blocking the signal transduction of B-cells. Besides, it has Immune action and improves anti-tumor immune response. Acalabrutinib can be used as a drug for the long term because of its high selectivity and few toxic effects of acatinib.

Ibrutinib is a small molecule BTK inhibitor that can covalently bind to cysteine residues in the active center of BTK, thereby inhibiting its activity. Bruton'styrosinekinase, the full name of BTK, transmits signals in the BCR signaling way and cytokine receptor signaling way, mediating the migration and adhesion of B cells. Ibrutinib can restrain the proliferation and survival of vicious B cells, which has been tested by Preclinical studies.

Conclusion: 

In the end, we want to give a conclusion about the topic of “acalabrutinib vs ibrutinib”. Acalabrutinib, a treatment for chronic lymphocytic leukemia (CLL), has a lower risk of adverse events, such as atrial fibrillation, compared to ibrutinib. Although the efficacy of these two drugs is similar, acalabrutinib is better tolerated than ibrutinib and has fewer side effects.