FDA Approves Selumetinib for Symptomatic Pediatric NF-1–Associated Inoperable Plexiform Neurofibromas

The FDA has approved selumetinib (Koselugo) granules and capsules for the treatment of pediatric patients 1 year and older with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PNs).1

The approval was supported by an adequate bridging between the oral granule and approved capsule formulations in a relative bioavailability study among healthy adults. The approval was also based on exposure matching between the pediatric patient populations in the phase 2 SPRINT study (NCT01362803) evaluating the capsule formulation in those 2 years and older, and the phase 1/2 SPRINKLE study (NCT05309668), which assessed the granule formulation in those 1 year and older. Similar exposure from the 2 formulations also supports extrapolation of efficacy from pediatric patients 2 years and older to those 1 year and older.

Regarding safety, prescribing information for selumetinib includes warnings and precautions for cardiomyopathy, ocular toxicity, gastrointestinal toxicity, skin toxicity, increased creatine phosphokinase levels, increased levels of vitamin E, increased bleeding risk with selumetinib capsules, and embryo-fetal toxicity. Notably, the incidences of warnings and precautions were updated to include data from a larger number of pediatric patients. No new safety signals were identified.

The recommended dose level of selumetinib based on body surface area is 25 mg/m2 orally, twice a day, until disease progression or unacceptable toxicity.

Of note, the FDA previously approved selumetinib in April 2020 for the treatment of pediatric patients 2 years and older with NF1 who have symptomatic, inoperable PNs.2

What Were the Background and Data From the SPRINT Study?

The open-label, multicenter, single-arm study evaluated the efficacy of selumetinib for the treatment of pediatric patients with NF1 and measurable target PN that is inoperable. In the efficacy population (n = 50), patients needed to have at least 1 significant morbidity related to the target PN. Of note, at least 20% of patients on the study had disfigurement, motor dysfunction, pain, airway dysfunction, bladder/bowel dysfunction, and visual impairment.

Additionally, the primary efficacy outcome was overall response rate (ORR), assessed by the National Cancer Institute and defined as the percentage of patients who achieved a reduction in tumor volume by 20% or greater on MRI and subsequent MRI within 3 to 6 months. In evaluable patients (n = 50), the ORR was 66% (n = 33; 95% CI, 51%-79%). Moreover, all patients had a partial response, and 82% of responders had sustained responses lasting 12 months or longer.

The most adverse effects (AEs) observed in at least 40% of patients were vomiting, rash, abdominal pain, diarrhea, nausea, dry skin, pruritus, musculoskeletal pain, fatigue, fever, acne, stomatitis, headache, and paronychia. Treatment of selumetinib may also cause cardiomyopathy, ocular toxicity, retinal pigment epithelial detachment and impaired vision, and increased creatinine phosphokinase levels. Notably, selumetinib should be withheld, dose-reduced, or permanently discontinued based on the severity of AEs.

What Is the Design of the SPRINKLE Study?

The ongoing phase 1/2 single-arm, open-label study evaluated the pharmacokinetics and safety of the granule formulation of selumetinib in patients aged 1 to 7 years with NF1-associated inoperable PNs.3

Patients included on the study have at least 1 measurable PN of at least 3 cm, a Lansky performance score of 70 or greater, and a body surface area of 0.4 m2 or greater and 1.09 m2 or less. Patients are not permitted on the study if they have confirmed or suspected malignant glioma or malignant peripheral nerve sheath tumor; a history of malignancy, except for malignancy treatment with curative intent and no known active disease at least 2 years before the first dose of the study treatment; or refractory nausea and vomiting, gastrointestinal disease, inability to swallow the formulated treatment, or previous significant bowel resection that could compromise their safety or affect the absorption or metabolism of selumetinib.

All patients were treated with selumetinib in 25 cycles and were required to participate in a long-term safety follow-up until they were aged 5 years.

References

1. 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 September 10, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-selumetinib-pediatric-patients-1-year-age-and-older-neurofibromatosis-type-1
2. FDA approves selumetinib for neurofibromatosis type 1 with symptomatic, inoperable plexiform neurofibromas. FDA. Updated April 13, 2020. Accessed September 10, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-selumetinib-neurofibromatosis-type-1-symptomatic-inoperable-plexiform-neurofibromas
3. Pharmacokinetics, safety and efficacy of the selumetinib granule formulation in children aged ≥1 to <7 years with NF1-related symptomatic, inoperable PN (SPRINKLE). ClincalTrials.gov. Updated May 14, 2025. Accessed September 10, 2025. https://clinicaltrials.gov/study/NCT05309668