FDA Approval Announcement
On November 19, 2025, AstraZeneca announced that the U.S. Food and Drug Administration (FDA) has approved Koselugo (selumetinib), a mitogen-activated protein kinase kinase 1 and 2 (MEK 1/2) inhibitor, for the treatment of adult patients with neurofibromatosis type 1 (NF1) with symptomatic, inoperable plexiform neurofibromas (PN).
In September 2025, the FDA approved selumetinib capsules and granules for pediatric patients aged 1 year and older.
Basis for Approval: Phase 3 KOMET Study
The approval was based on data from the randomized, double-blind, placebo-controlled Phase 3 KOMET study (NCT04924608), which evaluated the safety and efficacy of Koselugo in adult patients with NF1 and symptomatic, inoperable PN.
Study Design
Eligible patients (N=145) were randomized 1:1 to receive either Koselugo (n=71) or placebo (n=74) twice daily for 12 cycles (28 days per cycle).
Primary Endpoint
Confirmed objective response rate (ORR) at the end of Cycle 16, assessed by blinded independent central review per the Response Evaluation Criteria in Neurofibromatosis and Schwannomatosis.
Key Efficacy Results
Confirmed ORR: 20% (95% CI: 11–31) in the Koselugo group vs. 5% (95% CI: 2–13) in the placebo group
Duration of response (DOR) ≥ 6 months: 86% of responding patients in the Koselugo group
Median DOR: not reached (95% CI: 11.5–NE) in the Koselugo group
Safety Profile
The most common adverse reactions in adults were rash (all grades), acne-like dermatitis, and diarrhea.
Warnings and Precautions
Labeled warnings and precautions include:
Left ventricular dysfunction
Ocular toxicity
Gastrointestinal toxicity
Dermatologic toxicity
Elevated creatine phosphokinase
Elevated vitamin E levels
Increased bleeding risk (for Koselugo capsules)
Embryo-fetal toxicity
The adverse reactions observed in adult patients were consistent with the known safety profile of selumetinib.
Dosage Forms and Recommended Dose
Dosage Forms
Capsules: 10 mg, 25 mg
Oral granules: 5 mg, 7.5 mg
Recommended Adult Dose
25 mg/m² based on body surface area, administered twice daily until disease progression or unacceptable toxicity.
