FDA Approves Selumetinib for Patients with Neurofibromatosis Type 1

The US Food and Drug Administration (FDA) today approved selumetinib (Koselugo) to treat pediatric patients with neurofibromatosis type 1.

The drug is the first of its kind to be approved by the FDA to treat the genetic disorder of the nervous system which causes tumors to grow on nerves. Neurofibromatosis type 1 is a debilitating, progressive, and often disfiguring rare disease that begins early in life.

The FDA specifically approved selumetinib for pediatric patients >2 years old who have symptomatic, inoperable plexiform neurofibromas, which are tumors involving nerve sheaths and can grow anywhere in the body. Selumetinib is a kinase inhibitor that functions by blocking a key enzyme to stop tumor cells from growing. Neurofibromatosis type 1 is characterized by changes in skin coloring, neurologic and skeletal impairments, and risk for development of benign and malignant tumors. Approximately 30-50% of patients born with the rare disease develop >1 plexiform neurofibromas.

The approval came after the findings of a clinical trial conducted by the National Cancer Institute. Investigators enrolled pediatric patients who had neurofibromatosis type 1 and inoperable plexiform neurofibromas.

In the efficacy trial, the team have 50 patients the recommended dose and had routine evaluations of changes in tumor size and related morbidities during the trials. The patients took selumetinib 25 mg/m² orally twice a day until the disease progression or until they had unacceptable adverse reactions.

The overall response rate was 66%, which meant a majority of patients had a complete response and experienced more than a 20% reduction in plexiform neurofibromas volume on MRI that was confirmed on a subsequent MRI within 3-6 months. No patients had a complete disappearance of the tumor. Among the patients, 82% had a response lasting >12 months.

Additional outcomes included changes in plexiform neurofibromas-related disfigurement, symptoms, and functional impairments.

Common side effects included vomiting; rash; abdominal pain; diarrhea; nausea; dry skin; fatigue; musculoskeletal pain; fever; acneiform rash; stomatitis; headache; paronychia; pruritus. Additional serious side effects could include heart failure and ocular toxicity.