The U.S. Food and Drug Administration (FDA) has approved selumetinib (Koselugo) granules and capsules for pediatric patients aged 1 year and older with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN). The FDA previously approved selumetinib capsules for pediatric patients aged 2 years and older with NF1 who have symptomatic, inoperable PN.
The approval was based on adequate bridging between the oral granule and approved capsule formulations in a relative bioavailability study in healthy adults (Study 89) and exposure matching between the pediatric patient populations in the SPRINT phase II Stratum I study (capsule formulation, ≥ 2 years of age) and the SPRINKLE study (oral granule formulation, ≥ 1 year of age). Similar exposure between the formulations supports extrapolation of efficacy from pediatric patients ≥ 2 years of age to ≥ 1 year of age.
The selumetinib prescribing information includes warnings and precautions for cardiomyopathy; ocular, gastrointestinal, and skin toxicity; increased creatine phosphokinase; increased levels of vitamin E and increased bleeding risk (capsule formulation); and embryo-fetal toxicity. 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 selumetinib dose, based on body surface area, is 25 mg/m2 orally twice daily, until disease progression or unacceptable toxicity.
Selumetinib received Breakthrough Therapy and Orphan Drug designations.
