Alpha Biopharma's Zorifertinib Hydrochloride Tablets (Zorifer®) have been approved by the National Medical Products Administration (NMPA) in China for the first-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 (L858R) substitution mutations and central nervous system (CNS) metastases. This approval marks a significant advancement as Zorifertinib is the first drug globally to launch a registration clinical trial specifically targeting advanced NSCLC with CNS metastases and achieve positive results.
The approval is based on the results of the EVEREST trial, an international multi-center randomized controlled phase III trial. The study demonstrated a significant benefit in overall progression-free survival (PFS), with intracranial PFS reaching 17.9 months. Zorifertinib significantly reduced the risk of intracranial progression or death by 37% (P = 0.0018). These benefits were consistently observed across subgroups of patients with intracranial symptoms, EGFR L858R mutations, and more than 3 intracranial lesions.
EVEREST Trial Details
The EVEREST trial enrolled patients with advanced NSCLC and CNS metastases, including those with more severe disease and a higher number of intracranial lesions. According to Professor Wu Yilong from Guangdong Provincial People’s Hospital, the global lead Principal Investigator for the EVEREST study, the trial is the first large-scale registered international multi-center clinical trial for the treatment of lung cancer with CNS metastases to achieve statistically significant positive results. The study verified that all people with EGFR mutated NSCLC and brain metastases could benefit from Zorifertinib therapy.
Addressing Unmet Needs in NSCLC with CNS Metastases
Lung cancer is the most common and deadliest malignant tumor in China. In 2022, there were approximately 1.06 million new cases and 730,000 deaths. NSCLC accounts for about 85% of all lung cancer cases, and approximately 38.4% of Chinese NSCLC patients have EGFR mutation-positive tumors. Central nervous system metastasis is a common occurrence in NSCLC patients, with approximately 25% of EGFR mutation-positive NSCLC patients having CNS metastases at initial diagnosis, and 20% to 65% developing CNS metastases during the course of their disease. The poor blood-brain barrier permeability of many therapeutic drugs contributes to CNS progression during treatment.
Blood-Brain Barrier Penetration
Zorifertinib is uniquely designed as a non-substrate for blood-brain barrier efflux proteins, allowing it to penetrate the blood-brain barrier effectively. The blood-brain barrier, composed of tightly packed brain capillary endothelial cells, protects the brain by restricting drug entry. It contains efflux proteins like P-glycoprotein (P-gp, ABCB1) and breast cancer resistance protein (BCRP), which contribute to drug resistance in brain lesions. Zorifertinib's ability to bypass these efflux mechanisms enhances its efficacy in treating CNS metastases.
Company Statement
Zhang Yong, CEO of Alpha Biopharma, stated that Zorifertinib has demonstrated its therapeutic value and has received support from clinical experts and regulatory authorities. He anticipates that Zorifertinib will significantly enhance patient care by offering more effective treatments for individuals with lung cancer and brain metastases. The company collaborated with AstraZeneca to develop Zorifertinib, aiming to address the unmet clinical needs of patients with lung cancer and CNS metastases.
