Selumetinib (Koselugo®): A Comprehensive Monograph on the First-in-Class MEK Inhibitor for Neurofibromatosis Type 1

[Executive Summary]

Selumetinib, marketed under the brand name Koselugo®, represents a landmark achievement in targeted cancer therapy and the treatment of rare genetic disorders. It is a first-in-class, orally active, and highly selective inhibitor of mitogen-activated protein kinase kinase 1 and 2 (MEK1/2), key components of the RAS/RAF/MEK/ERK signaling pathway.[1] The development and approval of selumetinib have fundamentally altered the therapeutic landscape for neurofibromatosis type 1 (NF1), a debilitating genetic condition.

The core indication for selumetinib is the treatment of pediatric patients with NF1 who have symptomatic, inoperable plexiform neurofibromas (PN).[1] In the United States, it is approved for patients aged two years and older, while in the European Union, the approval is for patients aged three years and older.[5] Prior to selumetinib, the only management option for these often disfiguring and painful tumors was surgery, which was frequently not feasible due to the tumors' invasive nature and proximity to vital structures.

The approval of selumetinib was based on the robust and compelling results of the National Cancer Institute (NCI)-sponsored SPRINT trial. In this pivotal study, selumetinib demonstrated a confirmed Objective Response Rate (ORR) of 66%, signifying a volumetric reduction of at least 20% in PN size.[7] These responses were not only statistically significant but also durable and clinically meaningful, leading to notable improvements in patient-reported outcomes, including pain reduction, enhanced physical function, and better overall quality of life.[9]