Recently, according to foreign media reports, the European Commission (EC) has conditionally approved AstraZeneca and Merck’s Koselugo (selumetinib) for the treatment of symptomatic patients with neurofibromatosis type 1 (NF1) in children aged 3 years and older. , Inoperable plexiform neurofibroma (PN).

NF1 is a debilitating genetic disease that affects one in every 3,000 people in the world. In 30%-50% of NF1 patients, the tumor occurs in the nerve sheath (plexiform neurofibroma, PN) and may cause clinical problems such as malformations, motor dysfunction, pain, airway dysfunction, visual impairment, and bladder Or intestinal dysfunction. PN begins to develop in early childhood, has varying degrees of severity, and can reduce life expectancy by 8 to 15 years.

The approval is based on the results of the SPRINT Stratum 1 Phase II trial, which aims to evaluate the objective response rate of selumetinib monotherapy in pediatric patients with NF1-related inoperable PN and the impact on patient reports and functional outcomes. In the trial, Koselugo's objective response rate (ORR) was 66%. ORR is defined as the percentage of patients with complete (disappearance of PN) or partial remission (at least 20% reduction in tumor volume).

The safety and effectiveness data of the SPRINT Phase II clinical trial is one of the conditions for approval. In the SPRINT trial, selumetinib reduced NF1-related PN in 66% of patients and showed clinically significant improvement in PN-related symptoms. SPRINT data shows that Koselugo not only shrinks some children's tumors, but also reduces pain and improves their quality of life.

Koselugo (selumetinib) is an inhibitor of mitogen-activated protein kinase 1 and 2 (MEK1/2). MEK1/2 protein is an upstream regulator of the extracellular signal-related kinase (ERK) pathway. Both MEK and ERK are important components of the RAF-MEK-ERK pathway regulated by RAS, which is often activated in a variety of cancers. In animal experiments, Selumetinib can inhibit ERK phosphorylation in NF1 mice and reduce the number, volume and proliferation of neurofibromas.

Koselugo is approved in the United States and several other countries for the treatment of pediatric patients with NF1 and symptomatic, inoperable PN. Koselugo's clinical trials in adult NF1 PN patients are ongoing, and alternative formulations for pediatric patients are also scheduled to start this year.