Selumetinib Approved for Adults With Inoperable Plexiform Neurofibromas
FDA expands selumetinib approval to include treatment of adults with inoperable plexiform neurofibromas.
The U.S. Food and Drug Administration (FDA) has approved selumetinib (Koselugo) for adults with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN).
Selumetinib is an inhibitor that selectively binds to and inhibits the MEK1 and MEK2 proteins. These proteins work within the MAPK signaling pathway that regulates essential cellular processes such as growth, differentiation, and survival. Activating mutations in MEK proteins can cause the aberrant activation of the MAPK pathway and uncontrolled cell growth, ultimately resulting in tumor formation. By targeting MEK proteins, selumetinib disrupts this cancer-promoting signaling.
Selumetinib was originally approved in 2020 for pediatric patients aged 2 years and older with NF1 and symptomatic, inoperable plexiform neurofibromas. The indication was expanded to pediatric patients aged 1 year and older in September 2025. This latest approval further expands the indication to include adults as well.
The latest approval was based on the results of KOMET, a global, randomized, multicenter, double-blind, placebo-controlled phase III clinical trial. The trial enrolled 145 patients aged 18 years and older with NF1 and symptomatic PN tumors that could not be surgically removed. Patients were randomly assigned (1:1) to one of two groups—one in which patients received 25 mg/m2 of selumetinib twice daily and the other in which patients received a placebo. The confirmed objective response rate (ORR), which is the percentage of patients who showed partial or complete response, was used to assess the efficacy of the treatment.
Of the 71 patients on the selumetinib arm, 20% experienced a partial or complete response, compared to 5% of the 74 patients receiving the placebo. In the selumetinib arm, 86% of responses lasted at least six months.
The recommended selumetinib dose is 25 mg/m2 of body surface area orally twice daily, until disease progression or unacceptable toxicity.
NF1 is a genetic disorder that is estimated to occur in approximately 1 in 3,000 individuals. It affects the skin, skeletal system, and peripheral nervous system, which is the network of nerves outside the brain and spinal cord. Plexiform neurofibromas are tumors that arise from Schwann cells in approximately one-third to one-half of NF1 patients. Although they are typically benign, plexiform neurofibromas can cause substantial clinical complications, including chronic pain, functional impairment, and disfigurement. In some cases, these benign tumors can become malignant.
The FDA rendered its decision on November 19. Check this resource for updated information on all therapeutics regulated by the FDA.