AstraZeneca and MSD's MEK Inhibitor Selumetinib Submitted for Approval in China for Pediatric NF1 with Plexiform Neurofibromas

By Medicine Observer

On June 13, the latest announcement on the official website of the Center for Drug Evaluation (CDE) of the China National Medical Products Administration showed that AstraZeneca submitted a marketing application for the Class 5.1 new drug selumetinib capsules, which has been accepted. It has also been officially included in the priority review, intended for the treatment of pediatric patients aged 3 years and above with symptomatic, inoperable plexiform neurofibromas (PN) associated with neurofibromatosis type 1 (NF1). Public information indicates that selumetinib is an MEK inhibitor jointly developed by AstraZeneca and MSD. It is also the world's first drug to treat NF1, a rare and debilitating disease that occurs early in life.

Screenshot source: CDE official website

Selumetinib is an MEK inhibitor, and MEK is a key protein kinase in the RAS/MAPK signaling pathway. The product can selectively inhibit MEK1 and MEK2, thereby restoring the dysfunctional signaling pathway to normal and alleviating the condition of pediatric NF1 patients. Previously, this drug has been granted Orphan Drug Designation, Breakthrough Therapy Designation, and Priority Review by the U.S. FDA for the treatment of NF1. In April 2020, selumetinib was approved by the FDA for marketing (brand name: Koselugo) to treat NF1 in children aged 2 years and older who have symptomatic and/or progressive, surgically unresectable plexiform neurofibromas, becoming the first innovative therapy for the treatment of NF1.

According to public information from AstraZeneca and MSD (Merck & Co., Inc.), in July 2017, the two companies announced a global strategic collaboration in the field of oncology. Together, they are clinically developing and commercially promoting the world's first PARP inhibitor, olaparib, and the MEK inhibitor, selumetinib, for multiple cancer indications. The two parties will jointly develop combination therapies as well as monotherapy regimens for olaparib and selumetinib with other potential new drugs. At the same time, both companies will independently develop combination therapy regimens that pair olaparib and selumetinib with their respective PD-L1 and PD-1 inhibitors.

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

The CDE official website also shows that Selumetinib Capsules have been included in the priority review for the reason of "new varieties, dosage forms, and specifications of pediatric medicines that meet the physiological characteristics of children." It is intended for the treatment of NF1 pediatric patients aged 3 years and above who have symptomatic, inoperable plexiform neurofibromas.

Screenshot source: CDE official website

Previously, results from a clinical trial conducted at the National Cancer Institute in the United States showed that treatment with selumetinib achieved an overall response rate (ORR) of 66% in children with NF1 who had inoperable plexiform neurofibromas. All patients experienced partial responses. Among these patients, 82% had a duration of response lasting 12 months or longer.

NF1 is a rare, incurable genetic disorder with an incidence of approximately 1 in every 3,000 newborns. The disease is caused by mutations in the NF1 gene, which encodes neurofibromin protein. This genetic mutation 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 sheaths, resulting in plexiform neurofibromas.

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