20 billion USD BTK inhibitor competition is intensifying. Who is the real "king"?

Author: Duxing

It is reported that in the recent ESMO 2021, Nuocheng Jianhua disclosed the preliminary phase 1/2 study results of abutinib combined with the CD20 antibody MIL62 third-line treatment of patients with relapsed or refractory B-cell non-Hodgkin lymphoma in the form of a poster

Obrutinib is a new and highly selective BTK inhibitor developed by Nuocheng Jianhua

(1) BTK target

The full name of BTK is Bruton's Tyrosine Kinase, which is a key kinase in the BCR (B-Cell Receptor) pathway

Figure: B cell signal transduction pathway

Data source: HowNet

In view of the key role of BTK in regulating B cells, BTK has become a potential target for the treatment of malignant tumors and autoimmune diseases

(2) List of BTK inhibitors

At present, a total of five BTK inhibitors have been approved for marketing in the world, namely Ibrutinib, Acatinib, Zebutinib, Tirabrutinib and Obrutinib, which are listed in Japan

Figure: List of approved BTK inhibitors in the United States

Data source: Johnson & Johnson, BeiGene, Nuocheng Jianhua, etc.

Picture: List of approved BTK inhibitors in China

Data source: Johnson & Johnson, BeiGene, Nuocheng Jianhua, etc.

(1) Ibrutinib is the world's first listed BTK inhibitor, jointly developed by Johnson & Johnson/AbbVie

After the listing of Ibrutinib, sales have been surging, achieving sales of 9.

Chart: 2014-2020 global sales of ibrutinib (US$100 million)

Data source: Johnson & Johnson, AbbVie

Under the dual policy of medical insurance and drug donation, the price of ibrutinib has been greatly reduced

(2) Zebutinib (Baiyueze) was developed by BeiGene and is a second-generation selective BTK small molecule inhibitor

Figure: Comparison of the safety of Zebutinib, Ibrutinib and Acatinib

Data source: BeiGene

In November 2019, Zebutinib was approved by the FDA for the second-line treatment of MCL

Figure: Zebutinib and Ibrutinib in the treatment of WM head-to-head trial

Data source: BeiGene

On December 28, 2020, Baiyueze's two conditional approved indications for MCL and CLL/SLL were included in the National Medical Insurance Catalog, which will take effect on March 1, 2021

(3) Obutinib (Enokal) is a highly selective and irreversible small molecule BTK inhibitor, developed by Nuocheng Jianhua.

In terms of efficacy, the ICP-CL-00102 study included 99 evaluable MCL patients.

Figure: The mechanism of action of abutinib

Data source: Nuocheng Jianhua

In addition to tumor indications, abutinib also focuses on systemic lupus erythematosus and multiple sclerosis

(3) Summary

The prospect of BTK inhibitors is very broad.
According to the Frost & Sullivan report, the global BTK market peaks at US$20 billion
.
As the first listed BTK inhibitor, Ibrutinib is expected to be among the tens of billions of dollars club in 2021
.
At present, three types of BTK inhibitors have been approved for marketing in China, one imported and two domestically produced
.
However, from the perspective of the competitive landscape, Ibrutinib is in an absolute leading position by virtue of its first-mover advantage, with a market share of more than 80%; Zebutinib is catching up, and it is expected to achieve volume-for-price through inclusion in medical insurance at the end of 2020; Austria Although butinib has certain advantages in terms of efficacy and safety, its current share is low due to the late time to market
.
For abutinib, Nuocheng Jianhua must improve the sales team and accelerate the commercialization process on the one hand, and on the other hand, it must be included in the medical insurance as soon as possible to realize the price-for-quantity exchange
.
After all, translating clinical advantages into sales is the foundation of a drug
.