FDA Approves Selumetinib for Neurofibromatosis Type 1 in Pediatric Patients


Selumetinib becomes the first therapy approved for pediatric patients with Neurofibromatosis type 1.

Richard Pazdur, MD

Richard Pazdur, MD

The FDA has approved selumetinib (Koselugo; AstraZeneca) for the treatment of neurofibromatosis type 1 (NF1) in pediatric patients who are 2 years of age or older with symptomatic, inoperable plexiform neurofibromas (PN).1,2

Selumetinib, a kinase inhibitor, becomes the first therapy approved for pediatric patients who have NF1 with this decision. NF1 is a rare, progressive condition cause by a mutation or flaw in a particular gene and is most commonly diagnosed in early childhood and characterized by skin coloring, neurologic and skeletal impairments, and risk of development of benign and malignant tumors throughout life.

Patients are recommended to take selumetinib 25 mg/m2 orally twice per day on an empty stomach until disease progression or unacceptable toxicity. The FDA previously had granted this application priority review and breakthrough therapy designation. Selumetinib has also received fast track and orphan drug designations.

Approval from the FDA was based on the SPRINT trial, which was conducted by the National Cancer Institute (NCI) and showed an overall response rate (ORR) of 66% (n = 33; 95% CI, 51—79) in patients who received selumetinib.

“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. For the first time, pediatric patients now have an FDA-approved drug to treat plexiform neurofibroma, a rare tumor associated with NF1,” Richard Pazdur, MD, director, FDA Oncology Center of Excellence, acting director of Oncologic Diseases, FDA Center for Drug Evaluation and Research, said in a statement.

SPRINT was a phase 1/2 study that examined the safety and effectiveness of selumetinib in children and young adults with PN that cannot be completely removed by surgery. The efficacy results of the study included data from 50 of the patients who received selumetinib 25 mg/m2 orally twice per day. Patients continued on that dose until disease progression or until they experienced unacceptable adverse reactions. ORR was defined as the percentage of patients with a complete response and those who experienced more than a 20% reduction in PN volume on magnetic resonance imaging (MRI) that was confirmed on a subsequent MRI within 3—6 months.

READ MORE: Selumetinib Gets Breakthrough Designation for Neurofibromatosis Type 1

Changes in PN-related disfigurement, symptoms and functional impairments were considered secondary clinical outcomes of the study.

In addition to the previously mention ORR, all patients had a partial response to the drug, with 82% of responders sustaining responses lasting at least 12 months. Additionally, an independent central review of ORR was performed using the same response criteria and demonstrated an ORR of 44% (95% CI, 30—59).

The most common adverse events (AEs; occurring in >40% of patients) recorded among 74 pediatric patients with NF1 and PN who received selumetinib were vomiting, rash, abdominal pain, diarrhea, nausea, dry skin, fatigue, musculoskeletal pain, fever, acne, stomatitis, headache, paronychia, and pruritus.

Selumentinib can cause cardiomyopathy, ocular toxicity including retinal vein occlusion, retinal pigment epithelial detachment and impaired vision, and increased creatinine phosphokinase.


1. FDA approves selumetinib for neurofibromatosis type 1 with symptomatic, inoperable plexiform neurofibromas. FDA. fda.gov/drugs/resources-information-approved-drugs/fda-approves-selumetinib-neurofibromatosis-type-1-symptomatic-inoperable-plexiform-neurofibromas. Updated April 13, 2020. Accessed April 13, 2020.

2. FDA approves first therapy for children with debilitating and disfiguring rare disease [news release]. Silver Spring, MD: FDA. Published April 10, 2020. Accessed April 13, 2020. fda.gov/news-events/press-announcements/fda-approves-first-therapy-children-debilitating-and-disfiguring-rare-disease

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