Selumetinib Is Approved for Adults With Neurofibromatosis Type 1 With Plexiform Neurofibromas

Selumetinib (Koselugo, AstraZeneca Pharmaceuticals LP) received FDA approval for adults with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN). The decision was supported by data from the KOMET trial (NCT04924608).

NF1 PN is a rare, progressive genetic disorder that affects approximately 1 in 2500 individuals around the world. It is characterized by skin changes and the growth of tumors in the nervous system, including the brain, spinal cord, and nerves, which can lead to pain, mobility issues, and changes in appearance. Although some tumors can become cancerous, these growths in NF1 are typically benign.

Selumetinib is the only approved treatment for children and adults with NF1 PN as of 2025. In 2020, selumetinib was initially approved for pediatric patients ages 2 years and older. In 2025, this indicated was expanded to pediatric patients aged 1 year and older and now, adults.

Selumetinib selectively inhibits the MAPK pathway inhibitor, which plays a key role in cellular functions such as growth regulation, cell division, and differentiation. NF1 PN is one condition, among others, that can develop as a result to defects in this signaling pathway.

Selumetinib demonstrates significant clinical benefit across clinical trials, leading to its various approved indications. In the global, randomized, multicenter, double-blind, placebo-controlled KOMET trial, selumetinib yielded promising overall and duration of response.

The trial included 145 patients with NF1 PN, 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. They were randomized 1:1 to receive either selumetinib or placebo twice daily for 12 cycles.

The primary end point of the study was overall response rate (ORR) by end of cycle 16, with a secondary end point of duration of response (DOR). Data from the trial revealed promising outcomes. The investigators reported an ORR of 20% (95% CI: 11, 31) in the selumetinib arm compared with 5% (95% CI: 2, 13) for those receiving placebo (p-value 0.011), with 86% in the selumetinib arm having an observed DOR of at least 6 months.

Selumetinib’s safety was consistent with the known safety profile of the agent in pediatric patients. The prescribing information includes warnings and precautions for Left Ventricular Dysfunction, Ocular Toxicity, Gastrointestinal Toxicity, Skin Toxicity, Increased Creatine Phosphokinase, Increased Levels of Vitamin E and Increased Risk of Bleeding (KOSELUGO capsules), and Embryo-Fetal Toxicity.

Selumetinib’s expanded approval marks a meaningful advance for adults living with NF1 PN, a population that has long lacked effective treatment options. As the first and only FDA-approved therapy for NF1 PN across both pediatric and adult populations, selumetinib represents a critical step forward in addressing the unmet needs of individuals affected by this challenging genetic disorder.

REFERENCES

1. 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

2. What is NF1-PN?1-4. SpringWorks Therapeutics. Accessed November 19, 2025. https://www.nf1pn.com/

3. Neurofibromatosis type 1. Mayo Clinic. September 10, 2024. Accessed November 19, 2025. https://www.mayoclinic.org/diseases-conditions/neurofibromatosis-type-1/diagnosis-treatment/drc-20350495

4. Valletti D. FDA expands selumetinib to children with NF1-associated plexiform neurofibromas. Pharmacy Times. September 10, 2025. Accessed November 19, 2025. https://www.pharmacytimes.com/view/fda-expands-selumetinib-to-children-with-nf1-associated-plexiform-neurofibromas

5. Gorai S, Rathore G, Das K. Selumetinib-A Comprehensive Review of the New FDA-Approved Drug for Neurofibromatosis. Indian Dermatol Online J. 2024 Jun 26;15(4):701-705. doi: 10.4103/idoj.idoj_569_23

6. FDA approves selumetinib for adults with neurofibromatosis type 1 with symptomatic, inoperable plexiform neurofibromas. FDA. November 19, 2025. Accessed November 19, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-selumetinib-adults-neurofibromatosis-type-1-symptomatic-inoperable-plexiform