- Avitinib is an oral, third-generation EGFR-targeting drug developed by a domestic drug company with efficacy comparable to that of axitinib, and clinical trial studies are still ongoing.
- Evitinib has comparable benefits to axitinib, including highly selective, irreversible inhibition of EGFR mutated genes in lung cancer and the ability to overcome drug-resistant mutations.
Avitinib is an oral, small-molecule irreversible tyrosine kinase inhibitor (TKI). It has a dual role, inhibiting both epidermal growth factor receptor (EGFR) activity and T790M acquired resistance mutations, and is used in EGFR T790M mutation-positive non-small cell lung cancer (NSCLC) during treatment with a first- (gefitinib/erlotinib/eclotinib) or second-generation targeted agent (afatinib), or in disease progression after treatment.
Evitinib, a third-generation EGFR-targeted drug, was developed by a domestic pharmaceutical company and holds a global patent on the compound, and is an original new drug supported by the National Key Science and Technology Program for the Creation of New Drugs in the 12th Five-Year Plan. The company’s newest drug, Evitinib, was developed by a domestic pharmaceutical company with a global compound patent.
First-line anti-EGFR therapy for lung cancer
85% of lung cancer cases are NSCLC. in China, the main driver genes in NSCLC patients are EGFR, ALK, RET, ROS1, MET, HER2, BRAF and KRAS, among which EGFR mutation rate is the highest, about 35%.
In 2009, the IPASS study first demonstrated that EGFR inhibitors were effective in treating EGFR-mutated lung cancer (gefitinib reduced the risk of tumor progression or death by 52% relative to chemotherapy), and based on IPASS and subsequent studies, EGFR inhibitors represented by gefitinib were identified as the standard first-line therapy for patients with EGFR-mutated NSCLC.
Oxitinib emerges: overcoming the EGFR resistance challenge in lung cancer
During the use of first- and second-generation EGFR inhibitors, about 60% of NSCLC patients develop a T790M mutation in addition to the original EGFR mutation and develop resistance as a result.
The introduction of Osimertinib, a third-generation targeted agent that specifically addresses the EGFR T790M mutation, provides a solution to this challenge. 5.7 months, with an objective remission rate of 71%.
However, the cost of taking axitinib can be as high as 51,000 RMB per month, making it unaffordable for many patients. The domestic drug, everitinib, is expected to be comparable to oxitinib in terms of efficacy and more affordable for patients in China.
Evitinib: comparable to axitinib
Evitinib has a unique chemical structure, and clinical studies have found that it has three important features that first- and second-generation EGFR inhibitors do not have:
(1) Highly selective inhibition of EGFR mutant genes in lung cancer without affecting normal EGFR with physiological function, with a selective advantage of up to nearly 300-fold and thus very low side effects;
(2) It can overcome the drug-resistant mutation of EGFR gene and effectively inhibit the growth of drug-resistant cells;
(3) irreversibly inhibits the EGFR mutation gene in lung cancer, permanently blocking the oncogenic pathway of the EGFR mutation gene, with more reliable efficacy.
In phase I/II clinical trials, overall objective remission rates of 42% were achieved in patients with NSCLC resistant to first- and second-generation EGFR inhibitors treated with ivitinib, while objective remission rates and disease control rates of 52% and 94%, respectively, were achieved in patients in the 300 mg twice-daily dose group.
This confirms the effectiveness of ivitinib and provides the optimal dose for use in a phase II clinical trial – 300 mg twice daily.
In clinical trials, the most common drug-related adverse events were diarrhea, rash, and elevated alanine aminotransferase and aspartate aminotransferase, all of which recovered after stopping treatment, or reducing the dose. As of October 28, 2016, there were no adverse events that resulted in death. It is clear that not only is everitinib effective, but the safety profile is manageable.
Evitinib is currently advancing closely in clinical studies
In 2015, ivitinib initiated phase I clinical studies in China and the United States, respectively, becoming the first Chinese independent innovative drug to conduct clinical studies in China and the United States simultaneously; in early 2016, clinical evaluation of more than one hundred patients with advanced lung cancer has been completed, and the preliminary results are encouraging.
On August 25, 2016, we received the Phase II/III clinical approval from the former State Food and Drug Administration (CFDA), along with written support from the Drug Review Center, which established a conditionally approved clinical protocol for registration.
As of today, there are seven ongoing clinical trials of everolimus, four of which are enrolling patients and are being conducted at multiple medical institutions in China. For more information, please visit the China Drug Clinical Trials Registry:
(http://www.chinadrugtrials.org.cn/eap/clinicaltrials.searchlist) to view.