ChenTai Pharma's Next-Gen EGFR-TKI Zorifertinib Granted Clinical Trial Approval with 100% Blood-Brain Barrier Penetration Potential

According to the latest public notice from the Center for Drug Evaluation (CDE) of China's National Medical Products Administration, the Class 1 new drug zorifertinib tablets, submitted by Alpha Biopharma, has been granted tacit approval for clinical trials and is intended for the treatment of non-small cell lung cancer (NSCLC). Publicly available information indicates that zorifertinib is a next-generation EGFR-TKI specifically designed for patients with advanced NSCLC with central nervous system (CNS) metastases. Featuring a blood-brain barrier (BBB) penetration rate of up to 100%, it is currently undergoing Phase 2/3 clinical trials in patients with EGFR mutation-positive NSCLC with CNS metastases.

Founded in 2017, Alpha Biopharma is dedicated to the clinical development of innovative drugs worldwide and was co-founded by Mr. Zhang Yong and other partners. In the same year of its establishment, Alpha Biopharma entered into a collaboration agreement with AstraZeneca, aiming to precisely target the field of lung cancer brain metastases through its lead candidate drug, zorifertinib (AZD3759).

Brain metastases represent a major therapeutic challenge in advanced EGFR mutation-positive non-small cell lung cancer (NSCLC), with approximately 30% to 60% of patients developing brain metastases at various stages of the disease. However, the vast majority of EGFR tyrosine kinase inhibitors (EGFR-TKIs) are substrates for efflux proteins at the blood-brain barrier, resulting in limited intracranial drug concentrations and an inability to effectively control intracranial metastatic lesions. Due to the lack of effective therapies, these patients generally have a poor prognosis, frequently complicated by severe neurological deterioration, poor quality of life, and short overall survival.

According to information on the official website of Alpha Biopharma, as a next-generation EGFR-TKI, zorifertinib demonstrates potent blood-brain barrier penetration capability, achieving 100% penetration across the blood-brain barrier and attaining drug concentrations in the cerebrospinal fluid and brain tissue comparable to those in plasma.

Previously, the dose safety and clinical indications of the candidate drug were investigated in a Phase I clinical study named BLOOM. Results showed that among EGFR-TKI treatment-naïve patients, 18 patients had evaluable CNS target lesions, with an intracranial objective response rate (ORR) reaching 83% and an extracranial ORR reaching 72%, indicating that zorifertinib demonstrates clinically meaningful efficacy both intracranially and overall. In patients with leptomeningeal metastasis previously treated with EGFR-TKIs, the ORR reached 28%, and the disease control rate (DCR) reached 78%.

Regarding survival data, EGFR-TKI-naïve patients with brain metastases treated with zorifertinib demonstrated a median progression-free survival (PFS) of approximately 14 months. Even among patients with leptomeningeal metastases who had previously received EGFR-TKI therapy, the median overall survival (OS) was approximately 10 months.

Based on the positive clinical efficacy demonstrated in the BLOOM study for patients with leptomeningeal metastases, zorifertinib initiated the EVEREST (AZD3759-003) Phase 2/3 randomized controlled clinical trial in April 2018. The Global Principal Investigator for the EVEREST study is Professor Yilong Wu, and the target population comprises treatment-naïve patients with advanced EGFR mutation-positive NSCLC and brain metastases. This additional clinical trial approval for zorifertinib indicates that another new clinical trial for this product will soon be conducted in China.

References:

[1] Center for Drug Evaluation, National Medical Products Administration (CDE). Retrieved Aug 23, 2021, from http://www.cde.org.cn/news.do?method=changePage&pageName=service&frameStr=25#

[2] Expert Advisory Meeting for Alpha Biopharma's Investigational Drug Zorifertinib Held in Shanghai. Retrieved Jan 10, 2020, from https://www.chentaipharma.com/news/15/105.html

[3] Professor Myung-Ju Ahn: Zorifertinib (AZD3759) 100% Penetrates the Blood-Brain Barrier, Ushering in a New Era in the Treatment of Lung Cancer Brain Metastases. Retrieved Jan 14, 2020, from https://www.chentaipharma.com/news/15/120.html

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