FDA Approves Selumetinib for Adult NF1 With Plexiform Neurofibromas

The FDA has approved selumetinib (Koselugo) for the treatment of adult patients with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN).¹

The FDA’s decision is supported by positive data from the phase 3 KOMET trial (NCT04924608), a global, randomized, double-blind, multicenter study evaluating selumetinib’s efficacy and safety against placebo in adult patients with NF1 and symptomatic, inoperable PN.² Here, a total of 145 patients were randomized 1:1 to receive either selumetinib oral capsules at 10 mg/m² and the recommended dose of 25 mg/m² (n = 71) or placebo (n = 74) twice daily for 12 cycles.

The study measured the primary end point of confirmed objective response rate (ORR), including partial and complete responses, by the end of cycle 16, assessed by independent central review; secondary end points include patient-oriented measures of chronic pain intensity and quality of life.

Results from the KOMET trial showed a significantly higher confirmed ORR of 20% (95% CI, 11%-31%) in the selumetinib arm vs 5% (95% CI, 2%-13%) in the placebo arm (P =.011), suggesting selumetinib’s efficacy and potential to offer clinically meaningful benefits in adults.³ Of the patients who received selumetinib, a majority (86%) had a duration of response of 6 months or longer.

Regarding safety, the safety profile observed in adults was found to be consistent with the known safety profile of the agent. Selumetinib’s current prescribing information warns of the risk for events such as left ventricular dysfunction, ocular toxicity, gastrointestinal toxicity, skin toxicity, increased creatine phosphokinase, increased vitamin E levels, increased risk of bleeding, and embryo-fetal toxicity.¹

Selumetinib’s Development Pathway

Selumetinib’s development pathway has been marked by numerous positive FDA recognitions, from breakthrough therapy and orphan drug designations to full approvals.

The FDA initially approved selumetinib in April 2020 in the same indication for treatment of pediatric patients aged 2 years and older, based on findings from the phase 2 SPRINT Stratum 1 trial (NCT01362803).⁴

More recently, the FDA decreased the minimum age for selumetinib use, approving the agent in the same indication for the treatment of pediatric patients aged 1 year or older in September 2025.⁵ This decision was supported by data from the SPRINT Stratum 1 and phase 1/2 SPRINKLE (NCT05309668) studies.

This latest approval expands selumetinib’s application to adults, thereby addressing a critical unmet need in this population for whom there is only 1 other FDA-approved therapeutic option.

REFERENCES

1. FDA approves selumetinib for adults with neurofibromatosis type 1 with symptomatic, inoperable plexiform neurofibromas. US FDA. November 19, 2025. Accessed November 19, 2025. https://tinyurl.com/y4rkb7na

2. Efficacy and safety of selumetinib in adults with NF1 who have symptomatic, inoperable plexiform neurofibromas (KOMET). ClinicalTrials.gov. Updated October 17, 2025. Accessed November 19, 2025. https://clinicaltrials.gov/study/NCT04924608

3. Chen AP, Coyne GO, Wolters PL, et al. Efficacy and safety of selumetinib in adults with neurofibromatosis type 1 and symptomatic, inoperable plexiform neurofibromas (KOMET): a multicentre, international, randomised, placebo-controlled, parallel, double-blind, phase 3 study. Lancet. 2025;405(10496):2217-2230. doi:10.1016/S0140-6736(25)00986-9

4. FDA approves selumetinib for neurofibromatosis type 1 with symptomatic, inoperable plexiform neurofibromas. US FDA. April 13, 2020. Accessed November 19, 2025. https://tinyurl.com/4en6chas

5. FDA approves selumetinib for pediatric patients 1 year of age and older with neurofibromatosis type 1 with symptomatic, inoperable plexiform neurofibromas. FDA. September 10, 2025. Accessed November 19, 2025. https://tinyurl.com/5xffpwnx