FDA Approves Selumetinib for Children with Neurofibromatosis Type 1

The Food and Drug Administration (FDA) approved selumetinib (Koselugo; AstraZeneca, Wilmington, DE) for the treatment of children age 2 years or more who have neurofibromatosis type 1 (NF1). Selumetinib, a kinase inhibitor, is approved for treatment of symptomatic inoperable plexiform neurofibromas (PN) and is the first drug approved for treatment of people with NF1. 

In a clinical trial (NCT03326388), 66% of participants (n=50) treated with selumetinib 25 mg/m2  twice daily had at least a 20% reduction in PN volume on MRI that was confirmed on a subsequent MRI within 3 to 6 months. Although no participants had had complete disappearance of PN, 82% had a decrease in PN that lasted 12 months or more. 

Other clinical outcomes included changes in PN-related disfigurement, symptoms, and functional impairments. Although the sample sizes for each were small, there appeared to be a trend of improvement in PN-related symptoms or functional deficits during treatment. Common side effects for participants taking selumetinib were vomiting, rash, abdominal pain, diarrhea, nausea, dry skin, fatigue, musculoskeletal pain, fever, acneiform rash, stomatitis, headache, and pruritus. 

"Everyone's daily lives have been disrupted during the COVID-19 pandemic, and in this critical time we want patients to know that the FDA remains committed to making patients with rare tumors and life-threatening diseases, and their unique needs, a top priority. We continue to expedite product development for these patients," said Richard Pazdur, MD, director of the FDA's Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA's Center for Drug Evaluation and Research.

Selumetinib can also cause serious side effects including heart failure and ocular toxicity including retinal vein occlusion, retinal pigment epithelial detachment and impaired vision. Cardiac and ophthalmic assessments are needed before and during treatment with selumetinib. Creatinine phosphokinase (CPK) elevation may occur and should prompt an evaluation for rhabdomyolysis (breakdown of skeletal muscle due to direct or indirect muscle injury). Selumetinib should be withheld, dosage reduced, or dosage permanently discontinued based on the severity of adverse reactions. Further, selumetinib contains Vitamin E, and patients are at an increased risk of bleeding if their daily intake of Vitamin E exceeds the recommended or safe limits. Women of reproductive age, and men with female partners of reproductive potential should use effective contraception during treatment and for one week after the last dose.