Akatinib/Acalatinib: a second generation highly effective BTK inhibitor

Bruton's tyrosine kinase (BTK) plays a pivotal role in the treatment of B-cell malignancies, and oral BTK inhibitors have become an important means to combat such diseases. In this context, acalabrutinib, as an outstanding representative of the second generation, stands out due to its high selectivity and powerful covalent BTK inhibition ability. Compared with the first-generation BTK inhibitor ibrutinib, acotinib showed lower off-target activity in in vitro experiments, which means it may be better tolerated.

In the United States, acotinib was approved for the treatment of relapsed/refractory mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL) in 2017 and 2019 respectively. Not only that, acotinib has also been extensively tested in the treatment of other B-cell malignancies, covering both single-drug and combination-drug modes. The latest clinical research results show that acotinib can significantly extend the progression-free survival (PFS) of patients. Especially in patients with previously untreated CLL, acotinib demonstrated a significant improvement in PFS, whether or not combined with obinutuzumab.

From a safety perspective, acotinib has demonstrated a fairly high tolerability, with most reported adverse reactions being mild to moderate (the most common of which include headache and diarrhea). The most common serious reactions are infection and low white blood cell and red blood cell counts, and discontinuation of treatment due to adverse reactions is relatively rare.