Koselugo

Koselugo (selumetinib) is indicated as monotherapy for the treatment of symptomatic, inoperable plexiform neurofibromas (PN) in pediatric patients with neurofibromatosis type 1 (NF1) aged 3 years and above. It received Orphan Medicinal Product designation on 31 July 2018 (EU/3/18/2050) and a CHMP positive opinion on 22 April 2021. The CHMP did not agree to an accelerated assessment, but a Conditional Marketing Authorisation was granted based on a positive benefit-risk balance and the likelihood of providing comprehensive data.

In a study with a recommended dose of 25 mg/m2, the objective response rate (ORR) was 66% (95% CI: 51.2, 78.8). The median progression-free survival (PFS) was 1.3 years (95% CI: 1.1, 1.6), with a PFS hazard ratio of 0.08. The probability of remaining without progressive disease after 2 years was 30.4% (95% CI: 21.0, 40.3) and 94.7% (95% CI: 80.6, 98.7). Notable safety findings include 98.6% of patients experiencing at least one adverse event (AE), with 62.0% experiencing Grade ≥3 AEs. Common AEs (all CTCAE grades) included vomiting (82%), nausea (73%), and diarrhoea (77%). Grade 3 and above AEs included diarrhoea (15%), vomiting (8%), and nausea (1%).