Treatment for Neurofibromatosis Type 1–Associated Plexiform Neurofibromas Approved

The FDA has given the MEK inhibitor mirdametinib (Gomekli; SpringWorks) approval for the treatment of adult and pediatric patients aged ≥2 years with neurofibromatosis type 1 (NF1) who have symptomatic plexiform neurofibromas (PNs) not amenable to complete resection.¹ With the approval, SpringWorks was granted a rare pediatric disease Priority Review Voucher by the FDA.

The FDA approval of Gomekli is based on results from the phase 2b ReNeu trial, which enrolled 114 patients with NF1-PN aged ≥2 years (58 adults and 56 pediatric patients).10 Gomekli met the primary end point of confirmed objective response rate (ORR), as assessed by blinded independent central review, demonstrating a 41% ORR (N=24/58) in adults and 52% in children (N=29/56). Eighty-eight percent of adults and 90% of children with a confirmed response had a response of at least 12 months’ duration, and 50% and 48%, respectively, had a response of at least 24 months’ duration. Patients in both cohorts also experienced early and sustained significant improvements from baseline in pain and quality of life, as assessed across multiple patient-reported outcome tools.

The most common adverse events (>25%) reported in adults receiving Gomekli were rash, diarrhea, nausea, musculoskeletal pain, vomiting, and fatigue.¹ The most common adverse events (>25%) occurring in children were rash, diarrhea, musculoskeletal pain, abdominal pain, vomiting, headache, paronychia, left ventricular dysfunction, and nausea.¹

NF1 is a genetic disorder that currently affects approximately 100,000 children and adults in the United States. Patients with NF1 have approximately a 30% to 50% lifetime risk of developing PNs, which are tumors that grow in an infiltrative pattern along the peripheral nerve sheath and that can cause severe disfigurement, pain, and functional impairment.

“Patients with NF1-PN often face significant challenges with their health and have had limited treatment options to manage this devastating condition,” Christopher Moertel, MD, Medical Director, Pediatric Neuro-Oncology and Neurofibromatosis Programs, and Kenneth and Betty Jayne Dahlberg Professor of Pediatrics, University of Minnesota, and lead investigator of the ReNeu trial, said in a press release. “It was very encouraging in the ReNeu trial to see that Gomekli provided deep and durable responses, with a manageable safety profile that enabled patients to stay on therapy. This approval represents an important advance, especially for adults who previously did not have an approved treatment.”

Reference

1. FDA. FDA approves mirdametinib for adult and pediatric patients with neurofibromatosis type 1 who have symptomatic plexiform neurofibromas not amenable to complete resection [press release]. February 11, 2025. Accessed February 17, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-mirdametinib-adult-and-pediatric-patients-neurofibromatosis-type-1-who-have-symptomatic