FDA Approves First-Ever Drug for Pediatric Neurofibromatosis Type 1

The FDA approved selumetinib (Koselugo) to treat pediatric patients aged 2 years or older with neurofibromatosis type 1 (NF1). This is the first-ever therapy approved for this rare genetic disorder, which causes tumors to grow on nerves.

“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, in a statement.

NF1, which is usually diagnosed early in about 1 in every 3,000 infants, is a progressive disease. Between 30% and 50% of patients with NF1 have at least 1 or more plexiform neurofibromas (PNs) — tumors involving nerve sheaths that can grow throughout the body and affect organs.

Selumetinib is approved to treat patients with symptomatic, inoperable PNs. The drug is a kinase inhibitor that blocks a key enzyme that promotes PN cell grown.

The approval was based off a National Cancer Institute study involving 50 patients who received 25 mg/m² orally twice a day until disease progression or unacceptable adverse events (AEs). The primary endpoint was overall response rate (ORR), measured as the percentage of patients with a complete response and those who experienced more than a 20% reduction in PN volume within 3-6 months.

The ORR in the trial was 66%, and of these patients, 82% had a response lasting 12 months or longer. All patients had a partial response, and no patients had a complete disappearance of the tumor.

Common AEs for selumetinib include: vomiting, rash, abdominal pain, diarrhea, nausea, dry skin, fatigue, musculoskeletal pain (pain in the body affecting bones, muscles, ligaments, tendons and nerves), fever, acneiform rash (acne), stomatitis (inflammation of the mouth and lips), headache, paronychia (infection in the skin that surrounds a toenail or fingernail), and pruritus (itching).

Serious AEs can include heart failure and ocular toxicity. It is important that nurses and other healthcare providers perform cardiac and ophthalmic assessments prior to starting the agent, as well as throughout the duration of treatment. Selumetinib can also cause increased creatinine phosphokinase (CPK), which could lead to rhabdomyolysis. If this occurs, the drug should be withheld, dose reduced, or discontinued, based on how severe the AE is. Additionally, the FDA warned, selumetinib contains vitamin E, so patients who exceed vitamin E daily intakes may be at a higher risk of bleeding.

“We are committed to regulatory flexibility and providing extensive guidance to industry in an effort to bring drugs forward that fulfill unmet medical needs. Koselugo represents this commitment,” noted Pazdur. “For the first time, pediatric patients now have an FDA-approved drug to treat plexiform neurofibroma, a rare tumor associated with NF1,” Pazdur said.