On November 19, the U.S. Food and Drug Administration (FDA) approved selumetinib (Koselugo), a MEK inhibitor, for adults with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN). In September 2025, the FDA approved selumetinib capsules and granules for pediatric patients aged 1 year and older for this indication.
KOMET
Efficacy was evaluated in KOMET (ClinicalTrials.gov identifier NCT04924608), a global, randomized, multicenter, double-blind, placebo-controlled trial. Eligible patients were required to be 18 years of age or older with NF1 and symptomatic, inoperable PN. Inoperable PN was defined as a PN that could not be completely removed without risk for substantial morbidity due to encasement or close proximity to vital structures, invasiveness, or high vascularity.
A total of 145 patients were randomly assigned 1:1 to receive selumetinib or placebo twice daily for 12 cycles. The major efficacy outcome measure was confirmed overall response rate by the end of cycle 16, determined by independent central review (Response Evaluation in Neurofibromatosis and Schwannomatosis criteria). Duration of response was an additional efficacy outcome measure.
Confirmed overall response rate was 20% (95% confidence interval [CI] = 11%–31%) in the selumetinib arm compared to 5% (95% CI = 2%–13%) for those receiving placebo (P. = .011), with 86% of patients in the selumetinib arm having an observed duration of response of at least 6 months.
The prescribing information includes warnings and precautions for left ventricular dysfunction; ocular, gastrointestinal, and skin toxicity; increased creatine phosphokinase; increased levels of vitamin E and increased risk of bleeding (selumetinib capsules); and embryo-fetal toxicity. Adverse reactions observed in adult patients receiving selumetinib were consistent with the known selumetinib safety profile.
The recommended selumetinib dose, based on body surface area, is 25 mg/m2 orally twice daily until disease progression or unacceptable toxicity.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA's assessment. Selumetinib received Orphan Drug designation.
