FDA Approves Mirdametinib for NF1 Plexiform Neurofibromas in Children and Adults: First Oral MEK Inhibitor

What Is Mirdametinib and How Does It Treat Neurofibromatosis Type 1?

Mirdametinib (brand name Ojemda, developed by Day One Biopharmaceuticals) is a selective, oral inhibitor of mitogen-activated protein kinase enzymes MEK1 and MEK2. In neurofibromatosis type 1, loss-of-function mutations in the NF1 gene lead to constitutive activation of the RAS-MAPK signaling pathway, driving the growth of plexiform neurofibromas — benign but often debilitating nerve sheath tumors that can cause pain, disfigurement, airway compression, and functional impairment. Mirdametinib interrupts this pathway downstream of RAS, reducing tumor cell proliferation and survival.

NF1 affects approximately 1 in 3,000 individuals worldwide, and up to 50% develop plexiform neurofibromas. While selumetinib (Koselugo) was approved in 2020 for pediatric NF1 patients aged 2 and older, mirdametinib became the first MEK inhibitor approved for both children and adults with NF1 plexiform neurofibromas, addressing a significant unmet need for adult patients who previously had no FDA-approved pharmacological options. The drug is dosed as a twice-daily oral capsule, offering a treatment option across age groups.

What Were the Results of the ReNeu Clinical Trial?

The ReNeu trial was a single-arm, open-label Phase 2 study that enrolled patients aged 2 years and older with progressive, symptomatic, or life-threatening inoperable plexiform neurofibromas at multiple sites internationally. Patients received mirdametinib twice daily, with dosing based on body surface area. The primary endpoint was confirmed objective response rate (ORR) by blinded independent central review using volumetric MRI analysis, with a partial response threshold of ≥20% tumor volume reduction per REiNS (Response Evaluation in Neurofibromatosis and Schwannomatosis) criteria.

Results from the ReNeu trial demonstrated a confirmed ORR of approximately 41%, with an additional substantial proportion of patients achieving stable disease. Among responders, the majority maintained their response for more than 12 months. Symptom improvements were reported in a significant proportion of patients, including reduced pain, improved mobility, and decreased disfigurement. The safety profile showed manageable side effects including elevated creatine phosphokinase, acneiform rash, nausea, and diarrhea — consistent with the MEK inhibitor class. Ocular toxicity, a known class effect of MEK inhibitors, occurred as serous retinal detachment in a small percentage of patients, generally resolving with dose modification. Regular ophthalmologic monitoring is recommended during treatment.