Third-generation EGFR-TKI becoming a R&D hotspot
Sales of Osimertinib Approaching RMB 2 Billion in China in 2018
BPI-7711 of Beta Pharma into Phase III Clinical Trial.
Beta Pharma has recently started the Phase III clinical trial of BPI-7711 as a first-line therapy of non-small cell lung cancer (NSCLC), which has enrolled 294 participants, with gefitinib as the comparator.
BPI-7711 is a third-generation EGFR-TKI, making Beta Pharma the fourth Chinese pharmaceutical enterprises and hospital medical supply companies that enter the Phase III clinical trial of the variety following ACEA, Hansoh, and Allist.
Third-generation EGFR-TKI becoming a R&D hotspot
EGFR-TKI stands for epidermal growth factor receptor-tyrosine kinase inhibitor which is a targeted drug produced accompanying the cancer molecular typing and molecular biology development, and inhibits the whole pathway transduction and tumor growth by inhibiting nodes in intracellular signaling pathways, wherein, EGFR-TKI has become the drug of first choice recommended by NCCN for the big cancer type: EGFR-positive NSCLC (accounting for about 30% of lung cancers) owing to its prominent clinical efficacy. After over a decade of R&D, the EGFR-TKIs currently in the market are mainly divided into three generations:
Generation | Representative drug | Mechanism of action | Efficacy |
First-generation EGFR-TKI
| Gefitinib, erlotinib, icotinib (Chinese-produced) | Reversibly binding drug that binds to EGFR kinase domain through competing with ATP, to inhibit the activation thereof | Clinical effects significantly better than chemotherapy, with drug resistance situation |
Second-generation EGFR-TKI | Afatinib | Irreversibly binding drug that forms covalent attachments to the EGFR kinase domain, with the binding using covalent bond being more stable than the first-generation TKI, to thus improve the efficacy | Irreversible binding, with clinical effects better than the first-generation TKI, with drug resistance situation and big side effects |
Third-generation EGFR-TKI | Osimertinib | Binding to the small T790M mutation domain through a smaller binding region, to reach the treatment effect | The only effective drug for patients who have developed T790M mutation after treatment, with the clinical effects better than first-generation TKI, but with no effectiveness against rare resistance mutations |
(Organized according to public data)
The third-generation EGFR-TKI mainly targets patients with T790M resistance mutation. T790M gene mutation is the major mutation type (accounting for about 50%) of resistance after using EGFR-TKI. The first-generation and second-generation EGFR-TKIs are ineffective against T790M because the latter has a small domain, which is difficult for conventional drugs to bind to. As a result, the third generation has become the R&D hotspot of the giants.
Sales of Osimertinib Approaching RMB 2 Billion in China in 2018
Avitinib, the first Chinese-produced third-generation EGFR-TKI, to be marketed soon
As the first third-generation EGFR-TKI independently developed by ACEA...
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