FDA approves Gomekli (mirdametinib) for adult and pediatric patients with neurofibromatosis type 1

On February 11, 2025, the U.S. Food and Drug Administration approved the kinase inhibitor mirdametinib (Gomekli, SpringWorks Therapeutics, Inc.) for the treatment of adult and pediatric patients 2 years and older with neurofibromatosis type 1 (NF1) who have symptomatic plexiform neurofibromas (PN) that cannot be completely resected.

Efficacy was evaluated in ReNeu (NCT03962543), a multicenter, single-arm trial that enrolled 114 patients (58 adults, 56 pediatric patients) aged ≥2 years with symptomatic, inoperable NF1-associated PN causing significant morbidity. Inoperable PN is defined as a PN that cannot be completely surgically removed without substantial risk of morbidity due to encapsulation or proximity to vital structures, invasiveness, or high vascularity.

The primary efficacy outcome measure was confirmed overall response rate (ORR), defined as the percentage of patients with complete response (loss of target PN) or partial response (≥20% reduction in PN volume). Efficacy was evaluated by blinded independent central review using volumetric MRI analysis and a modified requirement to confirm efficacy within 2 to 6 months of the 24-cycle treatment phase according to the efficacy evaluation criteria for neurofibromatosis and schwannomatosis. Confirmed ORR was 41% (95% CI: 29, 55) in adults and 52% (95% CI: 38, 65) in the pediatric cohort.
The most common adverse reactions (>25%) in adult patients were rash, diarrhea, nausea, musculoskeletal pain, vomiting, and fatigue. The most common grade 3 or 4 laboratory abnormality (>2%) was elevated creatine phosphokinase.
The most common adverse reactions (>25%) in pediatric patients are rash, diarrhea, musculoskeletal pain, abdominal pain, vomiting, headache, paronychia, left ventricular dysfunction, and nausea. The most common grade 3 or 4 laboratory abnormalities (>2%) were decreased neutrophil count and increased creatine phosphokinase.
Mirdametinib can also cause left ventricular dysfunction and ocular toxicities, including retinal vein occlusion, retinal pigment epithelial detachment, and blurred vision. Depending on the severity of the adverse reaction, mirdametinib should be discontinued, the dose reduced, or the drug permanently discontinued.
Reference: https://www.gomekli.com/