Selumetinib’s Pediatric Approval Expanded for Neurofibromatosis Type 1 With Symptomatic, Inoperable Plexiform Neurofibromas

The FDA has approved selumetinib (Koselugo®, AstraZeneca Pharmaceuticals LP) capsules and oral granules for pediatric patients one year of age and older with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN). This approval extends the previously approved indication for selumetinib capsules, which was limited to patients ≥2 years of age.

Why This Approval Matters

This expanded approval makes selumetinib available to a younger pediatric population with NF1 and symptomatic, inoperable PN. Treatment options for these patients are limited, and the approval ensures access to therapy at an earlier age, which may be critical for symptom management and long-term disease control. The introduction of an oral granule formulation further provides a practical alternative for young children unable to swallow capsules.

Clinical Evidence Supporting Approval

The approval was supported by bridging data demonstrating adequate relative bioavailability between capsule and oral granule formulations in healthy adults (Study 89) and by exposure matching between pediatric populations in the SPRINT phase 2 Stratum I trial (capsule formulation, ≥2 years of age) and the SPRINKLE study (oral granule formulation, ≥1 year of age).

The comparable systemic exposure supports extrapolation of efficacy and safety findings from pediatric patients ≥2 years to ≥1 year of age.

Managing Adverse Events

The prescribing information for selumetinib includes warnings and precautions for cardiomyopathy, ocular toxicity, gastrointestinal toxicity, skin toxicity, elevated creatine phosphokinase, increased vitamin E levels, and bleeding risk (capsule formulation), and embryo-fetal toxicity. Safety data from expanded pediatric use were consistent with the existing safety profile, with no new adverse safety signals identified.

Dosing and Administration

Dosing is based on body surface area, with a recommended dose of 25 mg/m² orally twice daily, administered until disease progression or unacceptable toxicity. Selumetinib is available as capsules or oral granules, enabling flexible administration for pediatric patients as young as one year of age.

Highlights

What’s New as of September 10, 2025:

• Approved for pediatric patients ≥1 year of age with NF1 and symptomatic, inoperable plexiform neurofibromas (PN).
• Approval includes both capsules and new oral granules formulation.
• Supported by bridging bioavailability study (Study 89) and exposure matching between SPRINT (≥2 years) and SPRINKLE (≥1 year).

Previously Approved:

• Indication limited to pediatric patients ≥2 years of age with NF1 and symptomatic, inoperable PN.
• Approved only in the capsule formulation.
• Clinical evidence was based on SPRINT phase II Stratum I trial in patients ≥2 years.

References

Gross AM, Dombi E, Wolters PL, et al (2023). Long-term safety and efficacy of selumetinib in children with neurofibromatosis type 1 on a phase 1/2 trial for inoperable plexiform neurofibromas. Neuro Oncol, 25(10):1883-1894. DOI:10.1093/neuonc/noad086

Clinicaltrials.gov (2025). AZD6244 hydrogen sulfate for children with nervous system tumors. NLM identifier: NCT01362803.

Clinicaltrials.gov (2025). Pharmacokinetics, safety and efficacy of the selumetinib granule formulation in children aged ≥1 to <7 years with NF1-related symptomatic, inoperable PN (SPRINKLE). NLM identifier: NCT05309668.

Koselugo® (selumetinib) prescribing information (2024). AstraZeneca Pharmaceuticals LP. Available at: https://alexion.us/-/media/alexion_global/documents/regulatory/north-america/usa/2024/english/koselugo_uspi.pdf.

Updates to be posted at: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm

US Food and Drug Administration (2025). FDA approves selumetinib for pediatric patients 1 year of age and older with neurofibromatosis type 1 with symptomatic, inoperable plexiform neurofibromas. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-selumetinib-pediatric-patients-1-year-age-and-older-neurofibromatosis-type-1