FDA Approves First Treatment for Rare Genetic Disorder in Children


Neurofibromatosis type 1 (NF1) is a debilitating, progressive and often disfiguring disease that usually starts early in life.


The FDA has granted approval to the first treatment for neurofibromatosis type 1 (NF1) in pediatric patients 2 years of age and older.

Selumetinib (Koselugo, AstraZeneca) was approved by the FDA through Priority Review and Breakthrough Therapy designations, as well as Orphan Drug and Rare Pediatric Disease designations, in an effort by the FDA to maintain prioritizing search for treatment for life-threatening diseases during the COVID-19 crisis.

“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,” 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, said in a statement.

NF1 is a rare genetic disorder of the nervous system that causes tumors to grow on nerves, and often affects pediatric patients since its onset is early in life. The disease affects approximately 1 out of every 3000 infants, and is characterized by pigmentation, neurologic and skeletal impairment, and heightened risk for development of benign and malignant tumors throughout one’s life. Of those who have NF1, 30% to 50% develop 1 or more plexiform neurofibromas (PNs).

Selumetinib has been approved for use in particular patients who suffer from symptomatic, inoperable PN, in which tumors involving the nerve sheaths (the coating surrounding nerve fibers) can grow in any place in the body – including the face, extremities, spine, and areas where organs are affected. The drug works as a kinase inhibitor, resulting in prevention of tumor cell growth.

The approval was based on a clinical trial from the National Cancer Institute. In the trial, 50 pediatric patients with NF1 and inoperable PN – defined as PN that could not be completely removed without substantial morbidity risk – received the recommended dose of selumetinib and engaged in frequent evaluations of changes in tumor size and tumor-related morbidities during the trial. Dosage was 25 mg/m2 orally twice daily until the disease progressed, or until the patient experienced unacceptable adverse effects (AEs). The trial evaluated the overall response rate (ORR), defined as a 20% or more reduction in PN volume on MRI that was confirmed in a follow-up 3 to 6 months later. The ORR was 66% and all patients had a partial response; no patients had complete disappearance of the tumor, but of these patients, 82% had a response lasting 12 months or longer.

The most common AEs included 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).

Selumetinib can also cause serious AEs, including heart failure (manifested as ejection fraction decrease, or when the muscle of the left ventricle of the heart is not pumping as well as normal) and ocular toxicity (acute and chronic damage to the eye) including retinal vein occlusion, retinal pigment epithelial detachment and impaired vision.

“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.”


FDA Approves First Therapy for Children with Debilitating and Disfiguring Rare Disease. News Release. FDA; April 10, 2020. https://www.fda.gov/news-events/press-announcements/fda-approves-first-therapy-children-debilitating-and-disfiguring-rare-disease. Published April 10, 2020. Accessed April 13, 2020.

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