Alpha Biopharma received NMPA approval for Zorifertinib Tablets (Zorifer®), the world's first EGFR-TKI for lung cancer with brain metastases.

SHANGHAI, Nov. 20, 2024 /PRNewswire/ -- On November 20, 2024, the National Medical Products Administration (NMPA) announced on its official website that the NMPA approved the listing of Zorifertinib Hydrochloride Tablets (trade name: Zorifer®), a Class 1 innovative drug, developed by Alpha Biopharma. This product is indicated for the first-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) accompanied with epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 (L858R) substitution mutation and central nervous system (CNS) metastases.

Zorifertinib is the first drug in the world to launch a registration clinical trial specifically for advanced NSCLC with CNS metastases and achieve remarkable results. It is also the only* EGFR tyrosine kinase inhibitor (EGFR-TKI) currently available that was explicitly designed as non-blood-brain barrier efflux protein substrates and can penetrate the blood-brain barrier 100%.

The EVEREST trial, an international multi-center randomized controlled phase III trial of Zorifertinib, demonstrated its superior ability to control intracranial lesions. The trial enrolled patients with more severe disease, most of whom had EGFR L858R mutations or had more than 3 intracranial lesions. Zorifertinib showed a significant benefit in overall progression-free survival (PFS), with intracranial PFS reaching 17.9 months, and it significantly reduced the risk of intracranial progression/death by 37% (P = 0.0018). Furthermore, Zorifertinib demonstrated consistent and significant benefits in subgroups of patients with intracranial symptoms, EGFR L858R mutations, and more than 3 intracranial lesions.

As the global lead Principal Investigator (PI) for the EVEREST study, Professor Wu Yilong from Guangdong Provincial People's Hospital mentioned that while several drugs have been approved for EGFR mutated NSCLC, there is still a lack of clinical head-to-head randomized controlled studies specifically targeting drug therapy for lung cancer with CNS metastases. The EVEREST study is the world's first large-scale registered international multi-center clinical trial for the treatment of lung cancer with CNS metastases, and it has achieved statistically significant positive results. In the study, the therapeutic advantages of Zorifertinib in various subgroups were observed, and it was verified that all people with EGFR mutated NSCLC and brain metastases could benefit from Zorifertinib therapy. Among patients who were treated with third-generation TKI after progression, a trend of benefit in overall survival was also observed, suggesting that the combination or sequential therapy with third-generation TKI is expected to bring a better prognosis.

Zhang Yong, CEO of Alpha Biopharma, stated that the company is dedicated to developing innovative drugs that are urgently needed in clinical practice. We have collaborated with AstraZeneca to develop Zorifertinib, aiming to address the unmet clinical needs of patients with lung cancer and CNS metastases. Zorifertinib has demonstrated its therapeutic value during the clinical stage and has received support from clinical experts and regulatory authorities. It has become the world's first approved new generation EGFR-TKI specifically targeting lung cancer with CNS metastases. The company anticipates that Zorifertinib will significantly enhance patient care in the future, offering more effective treatments for individuals with lung cancer and brain metastases.

About Lung Cancer and Central Nervous System Metastasis

In China, lung cancer is the most common and deadliest malignant tumor. In 2022, there were about 1.06 million new cases of lung cancer diagnosed, leading to approximately 730,000 deaths, with non-small cell lung cancer (NSCLC) accounting for around 85% of all cases. In the Chinese NSCLC population, about 38.4% of patients have been found to have EGFR mutation-positive, which is identified as one of the driving genes for NSCLC formation.

Central nervous system metastasis is a common occurrence in NSCLC patients, with approximately 25% of EGFR mutation-positive NSCLC patients having CNS metastases at the time of initial diagnosis. Additionally, 20% to 65% of lung cancer patients will develop CNS metastases during the course of their disease. Poor blood-brain barrier permeability of therapeutic drugs is one of the reasons why patients experience CNS progression during treatment.

About Blood-Brain Barrier and Efflux Proteins

The blood-brain barrier is a protective shield that prevents drugs from entering the brain. It is made up of tightly packed brain capillary endothelial cells, surrounded by pericellular, astrocyte terminal, and basement membrane structures. This barrier has high resistance and low permeability, making it challenging for drugs to reach the brain. As a result, the brain can act as a safe haven for tumor cells, contributing to the progression of central nervous system (CNS) diseases.

The blood-brain barrier contains a large number of efflux proteins, such as P-glycoprotein (P-gp, ABCB1) and breast cancer resistance protein (BCRP), which are crucial for drug resistance in the development of brain lesions and the survival of tumor stem cells.

Remarks:

The "only ... currently available" in this article is valid as of the deadline of Oct. 10, 2024.

References

1. Cheng H, Perez-Soler R. Leptomeningeal metastases in non-small-cell lung cancer. Lancet Oncol. 2018 Jan;19(1):e43-e55.
2. Zhou Q, Yu Y, Xing L, et al. First-line zorifertinib for EGFR-mutant non-small cell lung cancer with central nervous system metastases: The phase 3 EVEREST trial. Med. Published online October 3, 2024.
3. Han B, Zheng R, Zeng H, et al. Cancer incidence and mortality in China, 2022[J]. Journal of the National Cancer Center, 2024.
4. Duma N, Santana-Davila R, Molina JR. Non-Small Cell Lung Cancer: Epidemiology, Screening, Diagnosis, and Treatment. Mayo Clin Proc. 2019, 94(8):1623-1640.
5. Zhang YL, Yuan JQ, Wang KF, et al. Threapleton D, Yang ZY, Mao C, Tang JL. The prevalence of EGFR mutation in patients with non-small cell lung cancer: a systematic review and meta-analysis. Oncotarget. 2016 Nov 29;7(48):78985-78993.
6. Preusser M, Winkler F, Valiente M, Manegold C, Moyal E, Widhalm G, Tonn JC, Zielinski C. Recent advances in the biology and treatment of brain metastases of non-small cell lung cancer: summary of a multidisciplinary roundtable discussion. ESMO Open. 2018 Jan 26;3(1):e000262.
7. Oncology Physician Branch of Chinese Medical Doctor Association, Oncology Branch of China International Exchange and Promotive Association for Medical and Health Care. Chinese Treatment Guidelines for Brain Metastases from Lung Cancer (2021 Edition). Chinese Journal of Oncology, 2021, 43(03): 269-281.
8. Shetty V, Babu S. Management of CNS metastases in patients with EGFR mutation-positive NSCLC. Indian J Cancer. 2019 Nov;56(Supplement):S31-S37.

SOURCE Alpha Biopharma