KOSELUGO

What it is

KOSELUGO is selumetinib sulfate, available as 10 mg and 25 mg hard capsules. Selumetinib is an orally available inhibitor of mitogen-activated protein kinase kinases 1 and 2 (MEK1/2), which are critical components of the RAS-regulated RAF-MEK-ERK pathway often activated in different types of cancers, and blocks MEK activity to inhibit growth of pathway-activated cells. This medicinal product is subject to additional monitoring in Australia to allow quick identification of new safety information.

Approved indications

— Adult and paediatric patients aged 2 years and older with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN).

Dosing overview

The recommended dosage of KOSELUGO is 25 mg/m² of body surface area (BSA), taken orally twice daily (approximately every 12 hours) until disease progression or unacceptable toxicity. Dosing in adult and paediatric patients is individualised based on BSA (mg/m²) and rounded to the nearest achievable 5 mg or 10 mg dose (up to a maximum single dose of 50 mg). KOSELUGO can be taken with or without food.

Key safety warnings

Left ventricular ejection fraction (LVEF) reduction has been reported in both paediatric and adult patients. LVEF should be evaluated before initiation of treatment to establish baseline values, and patients should have an ejection fraction above the institutional lower limit of normal. LVEF should be evaluated at approximately 3-month intervals, or more frequently as clinically indicated, during treatment. Patients should report any new visual disturbances. Adverse events of blurred vision have been reported, and isolated cases of retinal pigment epithelial detachment (RPED), central serous retinopathy (CSR) and retinal vein occlusion (RVO) have been observed. An ophthalmological evaluation prior to treatment initiation and at any time a patient reports new visual disturbances is recommended. Gastrointestinal toxicities, primarily including diarrhoea, vomiting, nausea, and stomatitis, occurred in patients who received KOSELUGO. Serious gastrointestinal toxicities, including perforation, colitis, ileus, and intestinal obstruction, occurred in an unapproved population of adult patients with multiple tumour types. Increased creatine phosphokinase (CPK) occurred in patients who received KOSELUGO, sometimes concurrent with myalgia. Rhabdomyolysis occurred in an unapproved adult population. Serum CPK should be obtained prior to initiating KOSELUGO and periodically during treatment.

Contraindications

Contraindications are hypersensitivity to the active substance or to any of the excipients, and severe hepatic impairment.

PBS listing

KOSELUGO 25 mg capsules and 10 mg capsules are each listed on the PBS with authority required restriction. The ex-manufacturer price is A$17,375.00 for the 25 mg capsule and A$6,950.00 for the 10 mg capsule, with the latest schedule date of 2026-05-01.

Regulatory history

KOSELUGO was first registered on the ARTG on 2 December 2021, with both the 25 mg and 10 mg capsule formulations registered under licence category RE. The PBAC initially did not recommend KOSELUGO in November 2022 for neurofibromatosis type 1 with symptomatic, inoperable plexiform neurofibroma(s) in paediatric patients, but recommended it in March 2024.