FDA Approves Mirdametinib for Patients With NF1-Associated Symptomatic, Inoperable Plexiform Neurofibromas
On February 11th, 2025, the US Food and Drug Administration (FDA) approved mirdametinib for adult and pediatric patients 2 years of age and older who have neurofibromatosis type 1 (NF1)-associated symptomatic plexiform neurofibromas (PN) not amenable to complete resection. This approval was based on results from the phase 2b ReNeu trial.
In this multicenter, single-arm trial, researchers enrolled 114 (adult, n = 58; pediatric, n = 56) patients with symptomatic and inoperable NF1-associated PN that could not be surgically removed due to the risk of significant morbidity. The primary end point was overall response rate (ORR) via blinded independent central review. A key secondary end point was safety.
At analysis, the confirmed ORR was 41% for adult patients and 52% for pediatric patients. The most common adverse reactions occurring in > 25% of adult patients included rash, diarrhea, nausea, musculoskeletal pain, vomiting, and fatigue. The most common grade 3/4 laboratory abnormality occurring in > 2% of adult patients was increased creatine phosphokinase. The most common adverse reactions occurring in > 25% of pediatric patients included rash, diarrhea, musculoskeletal pain, abdominal pain, vomiting, headache, paronychia, left ventricular dysfunction, and nausea. The most common grade 3/4 laboratory abnormalities occurring in > 2% of pediatric patients included decreased neutrophil count and increased creatine phosphokinase.
Mirdametinib can cause left ventricular dysfunction and ocular toxicities including retinal vein occlusion, retinal pigment epithelial detachment, and blurred vision. Based on the severity of adverse events, dose reductions or permanent discontinuation should be considered.
The recommended dose of mirdametinib is based on patient body surface area.
Source:
FDA approves mirdametinib for adult and pediatric patients with neurofibromatosis type 1 who have symptomatic plexiform neurofibromas not amenable to complete resection. Accessed on February 11, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-mirdametinib-adult-and-pediatric-patients-neurofibromatosis-type-1-who-have-symptomatic
