Few oligarchs compete?

On May 18, the CDE official website showed that the clinical application of Merck’s MK-1026 tablet was accepted by the State Food and Drug Administration
.

Introduction to BTK inhibitors

The full Chinese name of BTK (Bruton's Tyrosine Kinase) is Bruton's Tyrosine Kinase.
It is a key kinase in the B cell surface antigen (BCR) signaling pathway.
It plays an important role in the growth, development, and differentiation of B cells.
It is believed to be related to cancer and autoimmune diseases
.

BTK inhibitors and B cell malignancies

B-cell malignancies are the most common hematological malignancies
.

At present, 5 BTK inhibitors have been approved for marketing in the world, namely AbbVie and Johnson & Johnson’s ibrutinib, AstraZeneca’s acatinib, BeiGene’s Zebutinib, Gilead and Ono Pharmaceutical’s tirabrutinib.
And Nuocheng Jianhua's Obrutinib, of which Ibrutinib, Zebutinib and Obrutinib have been approved for listing in China
.

Advantages of MK-1026

       These listed BTK inhibitors all irreversibly bind to C481 in the BTK protein kinase domain through covalent binding, and ultimately achieve the purpose of inhibiting the activity of BTK enzyme.
They are all covalent inhibitors
.

       MK-1026 is a non-covalent BTK inhibitor designed to overcome resistance to covalent BTK inhibitors
.

       MK-1026 clinical efficacy

       The preliminary results of the dose-escalation phase I clinical trial announced at the 2019ASH (American Society of Hematology) conference showed that 47 patients with relapsed/refractory B-cell malignancies who had previously received median 4-line treatment received different doses (5, 10, 15 , 20, 30, 45, 65, 75 mg, once a day) After MK-1026 treatment, 30% of patients achieved PR, and 21% of patients had stable disease
.

       Another non-covalent BTK inhibitor-LOXO-305

       LOXO-305 is another non-covalent BTK inhibitor.
It is a reversible BTK inhibitor like MK-1026 and can target both wild-type and C481S mutant BTK
.

       The BRUIN study is a phase I/II clinical trial (n=28) using LOXO-305 to treat B-cell malignancies.
The study included 16 patients with CLL in the dose-escalation phase, and the median number of previous treatments for these patients was 4 In line therapy, 75% of patients had discontinued BTK inhibitor treatment (6 relapsed, 3 refractory, and 3 discontinued for other reasons)
.

       The results of the study reported at the 2019ASH conference showed that patients were relieved after receiving 6 dose levels (25-200mg per day) of LOXO-305
.

       With the in-depth research on BTK protein, BTK has become a popular target in the field of tumors and autoimmunity
.
At present, there are only 5 BTK inhibitors approved globally, which is in a situation where a small number of oligarchs compete
.
The new generation of differentiated non-covalent BTK inhibitors aims to overcome the limitations of existing BTK inhibitors
.
We believe that promising efficacy and tolerability data can prove its potential as an important treatment option for patients with B-cell lymphoma
.

       reference:

       1.
Buggy, JJ, & Elias, L.
Bruton Tyrosine Kinase (BTK) and Its Role in B-cell Malignancy.
International Reviews of Immunology, 2012, 31(2): 119–132.

       2.
Ash 2019– Merck gets Arqule ahead of data.
Evaluate Vantage.
December09,2019.
https:// .

       3.
Lilly Presents Interim Clinical Data from LOXO-305 Dose Escalation Trial in B-Cell Leukemias and Lymphomas at the American Society Hematology Annual Meeting.
Lilly Investors.
December 8, 2019.

       Editor in charge: Listen to the white