Expanded Pediatric Use of Selumetinib Approved for Inoperable Plexiform Neurofibromas
FDA expands selumetinib approval to include pediatric patients as young as 1 year with inoperable plexiform neurofibromas.
The U.S. Food and Drug Administration (FDA) has approved selumetinib (Koselugo) granules and capsules for pediatric patients 1 year of age and older with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas.
Selumetinib is a selective inhibitor of MEK1 and MEK2, proteins within the MAPK signaling pathway that regulates essential cellular processes such as growth, differentiation, and survival. Mutations may occur in MEK proteins, leading to aberrant activation of the MAPK pathway and unrestrained cellular proliferation ultimately resulting in tumor formation. By targeting these MEK proteins, selumetinib disrupts this cancer-promoting signaling.
Selumetinib capsules were previously approved for pediatric patients aged 2 years and older with NF1 and symptomatic, inoperable plexiform neurofibromas. The latest approval allows selumetinib to be administered to patients as young as 1 year.
The expanded approval was based on data from three clinical trials, which were SPRINT stratum I, Study 89, and SPRINKLE. Bridging data across these three trials supported the potential efficacy of selumetinib (in either the granule or capsule formulation) in patients 1 year and older.
In the phase II SPRINT stratum I trial—the results of which led to the earlier approval of selumetinib for patients 2 years and older—50 patients between 2 and 18 years of age who had inoperable plexiform neurofibromas were treated with the capsule formulation of selumetinib, with 68% of patients experiencing a response.
In the phase I Study 89 trial, 24 healthy adults were treated with selumetinib in different forms, and the concentration of the drug in their blood was monitored to understand how long the drug remains in the blood when administered in different forms. The granule form of the drug, which is the form of the drug easier to administer to younger children, was identified to be absorbed at a similar rate to the capsule form, suggesting that results from one formulation may be extrapolated to the other.
In the SPRINKLE study, children between 1 and 7 years of age with inoperable plexiform neurofibromas were treated with the granule formulation of selumetinib. Researchers compared drug exposure between two cohorts, one consisting of 17 patients from 1 to 3 years of age, and the other of 15 patients 4 to 7 years old. They found that selumetinib reached peak concentration within a similar time frame in both cohorts, suggesting similar drug exposures and supporting the extrapolation of data from the older cohort to the younger cohort.
Together, the three studies supported extrapolating the efficacy data from the SPRINT trial of patients aged 2 years and older treated with the capsule formation to patients as young as 1 year treated with either the capsule or granule formulation.
The recommended dose of selumetinib is 25 mg/m², based on body surface area, taken by mouth twice a day until disease progression or unacceptable toxicity.
NF1 is a genetic disorder that affects the skin, skeletal system, and peripheral nervous system, which is the network of nerves outside the brain and spinal cord. Plexiform neurofibromas, which occur in approximately 30% to 50% of NF1 patients, are tumors that are typically nonmalignant but carry a risk of malignant transformation. These tumors arise from Schwann cells, which are a type of cells in the peripheral nervous system. Despite their typically benign nature, plexiform neurofibromas can cause substantial clinical complications, including chronic pain, functional impairment, and disfigurement. NF1 has been estimated to occur in approximately 1 in 3,000 individuals.
The FDA rendered its decision on September 10, 2025. Check this resource for updated information on all therapeutics regulated by the FDA.