On November 15, 2019, zanubrutinib（trade name: BRUKINSATM）, a china-developed inhibitor of bruton's tyrosine kinase (BTK), received accelerated approval from the U.S. food and drug administration (FDA) for the treatment of adult intercellular lymphoma patients with at least one previous treatment. From the initial project development to the official approval of the market, the research and development of zanubrutinib took more than 7 years. It was completely developed by BeiGene co., LTD., and was the first anti-cancer drug approved by the FDA.
In 2013, the world's first BTK inhibitor, Ibrutinib was marketed in the United States, and in clinical trials, more than 98 percent of patients with slow-onset leukemia survived more than two years. Although the effect of Ibrutinib is good, its absorbability and safety need to be improved. BeiGene has a clear design idea for BTK inhibitors, which is to maximize the specific binding of inhibitors to BTK targets and minimize the off-target effect to reduce the incidence of adverse reactions. After a series of screening and testing, the team finally identified the final candidate molecule, zanubrutinib, in more than 500 compounds.
In clinical trials, zanubrutinib performed well. In a phase II study of Chinese patients, patients with relapsed and refractory tuber cell lymphoma had an overall remission rate of 84 percent after treatment with zanubrutinib, with 78 percent achieving a complete response. Based on the study, the FDA granted zanubrutinib "breakthrough therapy designation" earlier this year and accepted its application for a new drug. Now, the approval of zanubrutinib on the market is a breakthrough in the history of new drug innovation in China, marking that China's modern pharmaceutical industry has entered a new stage.
The crystal structure of the complex of zanubrutinib and BTK protein.