AstraZeneca/Mersk & Co.'s MEK Inhibitor Filed for Listing in China

On June 13, the latest announcement on the official website of the Center for Drug Evaluation (CDE) of the State Food and Drug Administration of China stated that AstraZeneca submitted a marketing application for a new drug of category 5.1, selumetinib capsules, and was accepted. At the same time, it has been officially included in the priority review. It is intended for the treatment of pediatric neurofibromatosis type 1 (NF1) patients 3 years of age and older with symptomatic, inoperable plexiform neurofibromatosis (PN). According to public information, selumetinib, a MEK inhibitor jointly developed by AstraZeneca and Merck & Co. (MSD), is also the world's first drug for the treatment of NF1, a rare disease that is debilitating in the early stages of life.

Selumetinib is an inhibitor of MEK, a key protein kinase in the RAS/MAPK signaling pathway. The product selectively inhibits MEK1 and MEK2, thereby restoring dysregulated signaling pathways, thereby relieving the condition of children with NF1. Previously, the drug has been granted orphan drug designation, breakthrough therapy designation and priority review qualification by the US FDA, and the indication is the treatment of NF1. In April 2020, selumetinib was approved by the FDA for marketing (trade name Koselugo), The first innovative therapy to treat NF1 in pediatric patients 2 years of age and older with symptomatic and/or progressive, inoperable plexiform neurofibromas.

According to the public information of AstraZeneca and Merck, in July 2017, the two parties announced that they had reached a strategic cooperation in the field of oncology on a global scale. Clinical development and commercial promotion for each oncology indication. The two parties will work together to develop olaparib and selumetinib in combination therapy and monotherapy with other potential new drugs. At the same time, the two companies will independently develop combination therapy regimens of olaparib and selumetinib with their respective PD-L1 and PD-1 inhibitors.

In China, selumetinib has received implied approval for multiple clinical trials for the treatment of symptomatic and/or progressive, inoperable NF1-related plexiform neurofibromas. According to the China Drug Clinical Trial Registration and Information Publicity Platform, AstraZeneca is conducting an international multicenter (including China) Phase 3 clinical trial to evaluate selumetinib in the treatment of symptomatic, inoperable adult NF1 with inoperable plexiform neurofibromas Efficacy and safety in subjects.

CDE's official website also shows that selumetinib capsules have been included in the priority review on the grounds of "new varieties, dosage forms and specifications of children's drugs that meet the physiological characteristics of children". Treatment of plexiform neurofibromas in pediatric patients with NF1.

Previously, results of a clinical trial conducted at the NationalCancer Institute showed that treatment with selumetinib resulted in an overall response rate (ORR) of 66% in children with NF1 with inoperable plexiform neurofibromas. All patients were in partial remission. Of these patients, 82% had a duration of remission of 12 months or longer.

NF1 is a rare, incurable genetic disorder with an incidence of approximately 1 in 3000 births. The disease is caused by a mutation in the NF1 gene that synthesizes neurofibromin, a gene mutation that disrupts the RAS/MAPK signaling pathway (RAS-RAF-MEK-ERK), leading to tumor growth. In 20% to 50% of patients with NF1, tumors develop on the nerve sheath, resulting in plexiform neurofibromas.