AstraZeneca's Selumetinib Capsules Granted Clinical Trial Approval in China for Pediatric NF1-Associated Plexiform Neurofibromas

By Baihuawen

On February 5, AstraZeneca’s Selumetinib capsules received implicit clinical trial approval for the treatment of symptomatic and/or progressive, inoperable plexiform neurofibromas (PN) associated with Neurofibromatosis Type 1 (NF1) in children and adolescents aged 3 years and older.

Neurofibromatosis (NF) is a benign disorder affecting the peripheral and central nervous systems, inherited in an autosomal dominant pattern. Based on differences in clinical manifestations and genetic loci, it is primarily classified into Neurofibromatosis Type 1 (NF1) and Neurofibromatosis Type 2 (NF2).

It is estimated that the incidence of NF1 is approximately 1 in 3,000 to 4,000 live births. Approximately 20–50% of patients with NF1 may develop plexiform neurofibromas, tumors that are often not amenable to complete surgical resection and carry a high risk of recurrence. Patients with NF1 may experience numerous complications, such as learning difficulties, visual impairments, spinal deformities and scoliosis, hypertension, and epilepsy. NF1 also increases an individual’s risk of developing other cancers, including malignant brain tumors and leukemia.

Selumetinib is a MEK 1/2 inhibitor. MEK is a key protein kinase in the RAS/MAPK signaling pathway, and the pathogenesis of NF1 involves tumor growth caused by NF1 gene mutations that disrupt the RAS/MAPK signaling pathway. The drug was granted orphan drug designation by the FDA in February 2018. In April 2019, it was granted Breakthrough Therapy designation by the FDA. Under a licensing agreement, AstraZeneca and Merck are jointly developing and commercializing selumetinib globally.

On November 14, 2019, the New Drug Application (NDA) for this drug submitted in the United States was accepted by the FDA and granted Priority Review status, with approval expected in the second quarter of 2020. If approved, it would become the first oral MEK1/2 inhibitor approved by the FDA for the treatment of neurofibromatosis type 1 (NF1).