FDA Approval Announcement
On September 10, the U.S. Food and Drug Administration (FDA) approved Koselugo (selumetinib) oral granules and capsules, an oral selective MEK inhibitor, for the treatment of pediatric patients aged 1 year and older with neurofibromatosis type 1 (NF1) and symptomatic, inoperable plexiform neurofibromas (PN). Previously, Koselugo was available only as a capsule for patients aged 2 years and older.
Basis for Oral Granule Approval
Approval of the oral granule formulation was based on:
A bioavailability study in healthy adults
Exposure matching between patients in the SPRINT Stratum I trial (evaluating capsules in patients aged ≥2 years) and the SPRINKLE trial (NCT05309668, currently evaluating oral granules in patients aged ≥1 year)
Studies showed comparable exposure between the two formulations, supporting extrapolation of efficacy to younger patients.
Dosage Forms and Administration
Oral Granules
Available strengths: 5 mg and 7.5 mg
Packaged in capsules; open capsule and mix with soft yogurt or puree (e.g., apple, banana, pear, strawberry) immediately before use
Administer within 30 minutes of preparation
Do not swallow the capsule shell
Do not mix with liquids or grapefruit/Seville orange-containing juices, purees, or jams
Capsules
Previously approved for patients aged 2 years and older
Dosage Recommendations
The recommended dose of Koselugo (capsules or oral granules) is based on body surface area.Dosage adjustment is recommended for patients with hepatic impairment, and those taking concomitant strong or moderate CYP3A inhibitors or fluconazole.
Warnings and Precautions
The prescribing information for Koselugo includes warnings and precautions for:
Cardiomyopathy
Ocular toxicity
Gastrointestinal toxicity
Dermatologic toxicity
Elevated creatine phosphokinase
Elevated vitamin E levels
Increased bleeding risk (capsules)
Embryo-fetal toxicity
The warning and precaution frequencies have been updated to include additional pediatric data; no new safety signals were identified.
