Selumetinib/Coselumab approved for neurofibromatosis type 1 in adults with plexiform neurofibromas

Selumetinib (Selumetinib) (Koselugo, AstraZeneca Pharmaceuticals LP) received FDA approval for adults with neurofibromatosis type 1 (NF1) with symptomatic, inoperable plexiform neurofibromatosis (PN). This decision is supported by data from the KOMET trial (NCT04924608).

NF1 PN is a rare, progressive genetic disorder that affects approximately 1 in 2,500 people worldwide. It is characterized by skin changes and the growth of tumors in the nervous system (including the brain, spinal cord, and nerves), which can cause pain, reduced mobility, and changes in appearance. Although some tumors can become cancerous, these growths in NF1 are usually benign.

As of2025, selumetinib is approved for use in children and adults with NF1 PN. In 2020, selumetinib was initially approved for pediatric patients 2 years of age and older. In 2025, this indication was expanded to pediatric patients 1 year of age and older, and now adults. Selumetinib selectively inhibits MAPK pathway inhibitors, which play a key role in cellular functions such as growth regulation, cell division and differentiation. NF1 PN is a disease that may result in defects in this signaling pathway.

Selumetinib demonstrated significant clinical benefit in clinical trials, leading to its various approved indications. Selumetinib produced promising overall and duration of responses in the global, randomized, multicenter, double-blind, placebo-controlled KOMET trial. The trial included 145 patients with NF1 PN, defined as PN that cannot be completely resected without substantial risk of morbidity due to encapsulation or proximity to vital structures, invasiveness, or high vascularity. They were randomized in a 1:1 ratio to receive selumetinib or placebo twice daily for 12 cycles.

The primary endpoint of the study is overall response rate (ORR) at the end of cycle 16, followed by duration of response (DOR). Trial data show promising results. The researchers reported an ORR of 20% (95% confidence interval: 11,31) in the selumetinib arm and an ORR of 5% (95% confidence interval: 2,13) u200bu200bin the placebo arm (p-value 0.011), with 86% of the DOR observed in the selumetinib arm being at least 6 months.

The safety profile of selumetinib was consistent with the known safety profile of this drug in pediatric patients. Prescribing information includes warnings and precautions for left ventricular dysfunction, ocular toxicity, gastrointestinal toxicity, skin toxicity, increased creatine phosphokinase, elevated vitamin E levels and increased risk of bleeding (KOSELUGO capsules), and embryo-fetal toxicity.

The expanded approval of selumetinib marks meaningful progress for adults withNF1 PN, a population that has long lacked effective treatment options. Selumetinib is a critical step toward addressing the unmet needs of individuals affected by this challenging genetic disease.

References: UpdatedNovember 19, 2025, https://www.pharmacytimes.com/view/selumetinib-is-approved-for-adults-with-neurofibromatosis-type-1-with-plexiform-neurofibromas