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Chronic lymphocytic leukemia is a tumor disease characterized by the aggregation of lymphocytes in the peripheral blood, bone marrow, spleen, and lymph nodes. The most important first-line treatment methods for this disease are mainly chemotherapy and chemical immunization.
BTK inhibitors came into being
Based on the above information, correspondingly, safer and more effective drugs came into being. Clinical studies have shown that BTK inhibitors have a significant efficacy in the treatment of CLL. The U.S. FDA has approved two oral BTK inhibitors for clinical use: Ibrutinib and Acalabrutinib1.
BTK is a member of the family of non-receptor protein tyrosine kinases, which are key kinases in the BCR signaling pathway that is activated when BCR binds to its corresponding antigen. The BCR pathway plays an important role in the pathogenesis of CLL. Therefore, inhibition of BTK has a very important role in the treatment of CLL.
So far, there are 3 BTK inhibitors listed worldwide, namely ibutinib, akatinib and zebutinib, and akatinib stands out for its safer and fewer adverse reactions.
As a second-generation BTK inhibitor, akatinib has become a "breakthrough drug" with stronger safety and selectivity. Not only that, but it also earned the title of "orphan drug". It has a significant inhibitory effect on the occurrence and development of B cell malignant tumors, and it has to be said that akatinib has a broad market prospect.
Second-generation BTK inhibitor - akatinib
Akatinib, a second-generation BTK inhibitor, is an irreversible BTK inhibitor mainly used for the treatment of mantle cell lymphoma. In 2017, the FDA approved akatinib for marketing primarily for the treatment of adult sleeve cell lymphoma (MCL) patients who had previously received a therapy; in 2019, based on phase III clinical studies ELEVATE-TN and ASCEND studies, akatinib was approved for the treatment of adult patients with CLL or small cell lymphoma (SLL).
Compared with the first generation of ibutinib, the biggest feature of akatinib is that it will be less toxic and has high specificity. Clinical data suggest that ibutinib has long-term efficacy in high-risk patients with initial treatment, relapse/refractory (RR) and del (17p). However, some patients with CLL experience adverse effects such as fatigue, joint pain, arrhythmias (such as atrial fibrillation), hypertension, and increased risk of bleeding after receiving ibutinib treatment, which are also the main causes of discontinuation of treatment.
Clinical efficacy of akatinib
In a foreign multicenter Phase I-II clinical trial, Byrd2 et al. administered oral akatinib to 61 patients with recurrent CLL, with a median age of 62 years and a median follow-up time of 14.3 months. Its final clinical data showed that the ORR rate (objective response rate) was 95%, of which 85% was partial response and 10% was partial response to lymphocytosis; the remaining 5% of patients were stable. In patients with 17p deficiency, the objective response rate was 100%, only one patient with CLL progressed, and only 10% of patients had more severe anemia, diarrhea, dyspnea and other adverse reactions.
Its pharmacokinetic results show that akatinib has no drug accumulation, and its half-life is about 1 hour.
Secondly, in the phase 3 ELEVATE-TN study, 535 patients, with a median age of 70 years and a median follow-up time of 28.3 months, showed that akatinib + obinyultizumab had a more significant effect than akatenib + chlorambucil (Clb), which significantly prolonged the progression-free survival (PFS) of patients. Among them, the estimated PFS rates of akatinib + obinyultuzumab and akatinib alone for 30 months were 90% and 82%, respectively.
The above clinical data show that the efficacy of akatinib is safer and more effective than that of traditional chemotherapy. Akatinib is of great value for the treatment of patients with CLL.
Akatinib price
However, so far, akatinib has not been listed in China, the price is relatively expensive, according to the export country, the price is also different. Patients can choose flexibly according to their own economic conditions!
Akatinib later outlook
So far, targeted BTK inhibitor therapy has gradually gained an irreplaceable position in patients with relapse and refractory treatment. The use of targeted drugs such as akatinib has revolutionized the treatment of B-cell malignancies. It is hoped that akatinib and similar drugs can be quickly listed in China, so that more CLL patients can use this drug, and it is believed that with the emergence of more treatment methods, the treatment of CLL will be further developed.
Resources
1Valla K, Flowers CR, Koff JL. Targeting the B cell receptor pathway in non-Hodgkin lymphoma. Expert OpinInvestig Drugs, 2018; 27(6): 513-522.
2Valla K, Flowers CR, Koff JL. Targeting the B cell receptor pathway in non-Hodgkin lymphoma. Expert OpinInvestig Drugs, 2018; 27(6): 513-522.