FDA approves selumetinib for adults with neurofibromatosis type 1 with symptomatic, inoperable plexiform neurofibromas
Regulatory approval: On Nov 19, 2025, the FDA approved selumetinib (KOSELUGO) for adults with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas. Approval was supported by the randomized, double-blind, placebo-controlled KOMET trial (NCT04924608), in which confirmed ORR by end of Cycle 16 was 20% with selumetinib vs 5% with placebo (p=0.011); 86% of responders had DOR ≥6 months. Label includes multiple safety warnings.
FDA approval (Nov 19, 2025)
The US Food and Drug Administration (FDA) approved selumetinib (KOSELUGO; AstraZeneca Pharmaceuticals LP) for adults with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN). The FDA previously approved selumetinib capsules and granules for pediatric patients ≥1 year for this indication.
Supporting evidence: KOMET (NCT04924608)
Efficacy was evaluated in KOMET, a global, randomized, multicenter, double-blind, placebo-controlled trial enrolling patients ≥18 years 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/close proximity to vital structures, invasiveness, or high vascularity.
A total of 145 patients were randomized 1:1 to selumetinib or placebo twice daily for 12 cycles. The primary outcome was confirmed overall response rate (ORR) by end of Cycle 16 by independent central review using Response Evaluation in Neurofibromatosis and Schwannomatosis criteria; duration of response (DOR) was also assessed.
Confirmed ORR was 20% (95% CI, 11–31) with selumetinib vs 5% (95% CI, 2–13) with placebo (p=0.011). Among responders in the selumetinib arm, 86% had observed DOR ≥6 months.
Safety and dosing
Prescribing information includes warnings/precautions for left ventricular dysfunction, ocular toxicity, gastrointestinal toxicity, skin toxicity, increased creatine phosphokinase, increased vitamin E levels and increased risk of bleeding (capsules), and embryo-fetal toxicity. Adult adverse reactions were reported as consistent with the known selumetinib safety profile.
Recommended dose (BSA-based): 25 mg/m² orally twice daily until disease progression or unacceptable toxicity. Selumetinib received orphan drug designation.