Recently, WJ13404 Tablet, a first-in-class of Suzhou Junjing Biosciences, has been submitted for clinical application (acceptance No.: CXHL2200202/3). WJ13404 Tablet is a fourth generation of EGFR-TKI (EGFR inhibitor). In September 2020, Junshi Biosciences and Wigen Biomedicine announced an agreement to jointly develop, manufacture and commercialize the fourth generation of EGFR-TKIs globally.
As the "golden" mutation in lung cancer, EGFR is considered as one of the fastest growing and most drug-rich mutations among the targeted drugs, and there are currently three generations of EGFR-TKIs on the market. As the main treatment product for lung cancer patients with EGFR mutations, EGFR-TKIs is promising in market. So what is the market outlook for the fourth generation EGFR-TKIs?
EGFR Inhibitors - God's Gift to the East
Epidermal Growth Factor Receptor (EGFR), a transmembrane tyrosine kinase receptor, plays an important role in the growth, apoptosis, metastasis and proliferation of cancer cells. Specifically, when EGFR is normally expressed, it can be involved in cell growth and division. It is considered as a regulatory switch for human epidermal cells. When EGFR mutates, it overexpresses the tyrosine kinase receptor, which in turn binds to an excess of epidermal growth factor, leading to tyrosine kinase overactivation and uncontrolled cell growth and division.
EGFR inhibitors inhibit the activation of tyrosine kinases by competing with endogenous ligands to bind EGFR and block the EGFR signaling pathway, thereby producing a range of biological effects such as inhibiting the proliferation and metastasis of tumor cells and promoting the development of apoptosis in tumor cells.
It is worth noting that EGFR mutations account for less than 10% of patients with NSCLC in Europe and America, but more than 30% of patients in Asia. Mutations that are rare in European and American patients are significant for Asian patients. It is for this reason that EGFR-TKIs have been called God's gift to the East.
Iteratively Upgraded EGFR-TKIs
The advent of EGFR-TKIs is arguably a landmark event in lung cancer treatment. First-line therapy with EGFR-TKIs can prolong progression-free survival (PFS), improve quality of life and reduce the incidence of serious side effects in patients with EGFR mutations compared to those receiving standard chemotherapy.
However, drug resistance is a constant topic. EGFR-TKIs have been iteratively updated from "birth" to the present in response to the development of resistance in patients' treatment. Currently, the first, second and third generations of EGFR-TKIs are on the market and a number of companies are creating the fourth generation of EGFR-TKIs.
The first generation of EGFR-TKIs are reversible targeted drugs that inhibit the activation of EGFR kinase by competing with ATP for binding to its structural domain. The first generation of EGFR-TKIs are represented by Gefitinib, Erlotinib and Icotinib. However, despite its efficacy, most patients develop resistance to the drugs after 1-2 years of use.
The second generation of EGFR-TKIs are irreversible targeted drugs, represented by Afatinib and Dacomitinib. Due to their use of covalent bonds to irreversibly bind the EGFR kinase active center site, their clinical efficacy has improved compared to the first generation EGFR-TKIs and they are able to overcome the problem of drug resistance to a certain extent. However, the second generation of EGFR-TKIs have not shown better overall survival rates for patients in clinical trials and they can also cause serious side effects such as diarrhea and skin rash.
The third generation of EGFR-TKIs are also irreversible targeted drugs, represented by Osimertinib, which efficiently inhibits EGFR-sensitive mutations and EGFR T790M-resistant mutations, while also showing good efficacy against brain metastases. Osimertinib even set the longest median Progression-Free Survival (mPFS) and median Overall Survival (mOS) in the history of EGFR-TKIs, reaching 18.9 months and 38.6 months respectively, undoubtedly a new peak in treatment history.
As one of the most prevalent cancers in the world, lung cancer has a large patient population, both abroad and at home, so its market outlook is naturally not bad. The sales volume of Gefitinib reached US$67 million in 2002, the first year of marketing; With FDA approval for market...
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