Mirdametinib in symptomatic neurofibromatosis type 1 plexiform neurofibromas

Neurofibromatosis type 1 (NF1) is a rare genetic disorder frequently complicated by plexiform neurofibromas (PNs) - benign but often morbid tumors associated with pain, disfigurement, and functional impairment. Mitogen-activated protein kinase (MEK) inhibitors have emerged as an approach for the management of NF1-PNs.

This review summarizes the pharmacology, mechanism of action, preclinical rationale, and clinical development of mirdametinib, a selective MEK1/2 inhibitor approved for the treatment of symptomatic, inoperable NF1-PNs in children and adults. We review key pharmacokinetic and pharmacodynamic properties, preclinical data supporting MAPK/ERK pathway inhibition, and outcomes from mirdametinib clinical trials. Emphasis is placed on efficacy outcomes, patient-reported benefits, durability of response, safety profile, and regulatory milestones. Emerging evidence from indirect treatment comparisons and early combination strategies is also discussed to contextualize mirdametinib within the evolving therapeutic landscape.

Mirdametinib represents a meaningful advance in the management of NF1-PNs, offering durable tumor volume reduction, improvements in pain and quality of life, and a manageable safety profile across age groups. While head-to-head comparisons with other MEK inhibitors are lacking, available evidence suggests a favorable balance of efficacy and tolerability that may support its use as a first-line systemic option in appropriately selected patients.