Zerini (Zolitrectinib Hydrochloride Tablets), a Novel First-in-Class EGFR-TKI with Full Blood-Brain Barrier Penetration, Approved in China for First-Line Treatment of EGFR-Mutant NSCLC with CNS Metastases

Nov 22, 2024 07:31 CST Updated 07:31

AstraZeneca

Pharmaceutical Technology Research and Development Provider

Alpha Biopharma

Innovative Drug Developer

On November 20, according to the official website of the National Medical Products Administration, Zorifertinib Hydrochloride Tablets (brand name: Zerenee), a Class 1 new drug co-developed by AstraZeneca and Alpha Biopharma, has been approved for marketing in China.

This medication is suitable for the first-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations, accompanied by central nervous system (CNS) metastases, offering a new treatment option for patients.

Lung cancer is the malignant tumor with the highest incidence and mortality rate in China. In 2022, China had approximately 1.06 million newly diagnosed lung cancer patients, and about 730,000 lung cancer patients died. Among them, NSCLC accounts for about 85% of all lung cancers. EGFR mutation-positive has been identified as one of the driver genes for NSCLC tumorigenesis, with an incidence rate of EGFRm+ in the Chinese NSCLC population of approximately 38.4%.

Central Nervous System Metastasis in NSCLC PatientsCentral nervous system (CNS) metastasis is one of the common metastatic sites in patients with non-small cell lung cancer (NSCLC). Approximately 25% of EGFR mutation-positive NSCLC patients present with CNS metastasis at initial diagnosis, and 20%-65% of lung cancer patients will develop CNS metastasis during the course of their disease. Poor blood-brain barrier permeability of therapeutic drugs is one of the reasons for CNS progression during the treatment process.

Currently marketed EGFR tyrosine kinase inhibitor (TKI) drugs struggle to cross the blood-brain barrier, resulting in poor control of intracranial tumors. Zoritini is a next-generation EGFR-TKI specifically designed for treating advanced non-small cell lung cancer with central nervous system metastases, demonstrating full capability to penetrate the blood-brain barrier.

In Phase 1 and Phase 2 clinical studies, Zolitinib demonstrated favorable systemic and intracranial antitumor activity. According to literature reports, preclinical studies found that after administration of zolitinib, the drug could reach the same concentration in blood, cerebrospinal fluid, and brain tissue, proving that the product can 100% penetrate the blood-brain barrier.

According to a previous report by Alpha Biopharma, Zoritini completed the world's first international multicenter randomized controlled Phase III clinical study, EVEREST, specifically targeting patients with CNS metastases. The study enrolled patients with advanced non-small cell lung cancer who had EGFR-sensitive mutations, were untreated, had not received radiotherapy, had or did not have neurological symptoms, and had CNS metastases. Patients were randomly assigned in a 1:1 ratio to receive either Zoritini or a first-generation EGFR-TKI (control group). The primary endpoint of the study was progression-free survival (PFS) assessed by blinded independent central review (BICR) based on RECIST 1.1 criteria.

In October this year, the latest results of the EVEREST study published in CELL’s subsidiary journal MED showed that, compared with the control group, zorifertinib demonstrated a significantly longer median PFS (9.6 months vs. 6.9 months). Zorifertinib also significantly extended intracranial PFS compared to the control group. The overall survival (OS) is not yet mature; 60% of patients in the zorifertinib group were able to receive subsequent third-generation EGFR-TKI treatment, and among these patients, the estimated median OS for zorifertinib was 37.3 months (over three years). In terms of safety, the safety profile of zorifertinib was consistent with previously reported data.

Researchers believe that, compared with the first-generation EGFR-TKI, zoritini significantly improved overall and intracranial PFS; adverse reactions were controllable. The sequential treatment of zoritini with the third-generation EGFR-TKI showed potential in extending patients' OS. The study results support zoritini as a new, well-validated first-line treatment option for EGFR-mutated non-small cell lung cancer patients with CNS metastases.

The approval and market launch of Zorifertinib provides a new treatment option for NSCLC patients with EGFR-sensitive mutations accompanied by CNS metastases, enabling these patients to receive more effective treatment beyond traditional methods. As the clinical application of Zorifertinib continues to expand, we can expect to see more data on the drug's efficacy and safety.

Source |Official Website of China National Medical Products Administration, Alpha Biopharma Official Website

Writing｜Anna.An

Editor | Swagpp

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