Dr Moertel on the FDA Approval of Mirdametinib for NF1-Associated Plexiform Neurofibromas

“The approval of mirdametinib is significant because this a highly selective MEK inhibitor that will provide benefit to both adults and children with neurofibromatosis type 1 who have plexiform neurofibromas that are not amenable to surgery and are causing significant quality-of-life or pain issues.”

Christopher L. Moertel, MD, pediatric neuro-oncologist; professor; director, Pediatric Neuro-Oncology Fellowship Program, Division of Pediatric Hematology/Oncology; faculty, Department of Pediatrics; medical director, Pediatric Neuro-Oncology and Neurofibromatosis Programs; co-medical director, Katie Hageboeck Children's Cancer Research Fund Clinic; clinical neuro-oncology leader, Brain Tumor Program; and The Kenneth and Betty Jayne Dahlberg Professor, University of Minnesota School of Medicine, discusses the FDA approval of mirdametinib (Gomekli) for the treatment of adult and pediatric patients with neurofibromatosis type 1 (NF1)–associated plexiform neurofibromas (PN).

On February 11, 2025, the FDA approved mirdametinib for adult and pediatric patients 2 years of age and older with NF1 who have symptomatic PN not amenable to complete resection.

The regulatory decision was supported by data from the phase 2b ReNeu trial (NCT03962543), which demonstrated that treatment with mirdametinib led to significant reductions in tumor volume, pain relief, and improvements in quality of life for patients with NF1-PN that was not amenable to surgical resection. The trial enrolled both adult and pediatric patients and evaluated mirdametinib’s efficacy and safety in this patient population.

Findings that supported the approval showed that adult patients (n = 58) achieved a confirmed overall response rate (ORR) of 41% (95% CI, 29%-55%); pediatric patients (n = 56) experienced a confirmed ORR of 52% (95% CI, 38%-65%).

Beyond tumor reduction, the trial demonstrated significant clinical benefits in symptom management. Patients reported marked reductions in pain severity, which translated into improved daily functioning and quality of life.

Moertel emphasizes that this approval is particularly meaningful for adult patients with NF1-PN, who have historically lacked FDA-approved treatment options.

The approval of mirdametinib represents a significant advancement in the treatment landscape for NF1-PN, Moertel concludes. Future research may focus on optimizing long-term disease management strategies and evaluating combination approaches to further enhance clinical outcomes.