FDA Approves Mirdametinib for Neurofibromatosis Type 1

The US Food and Drug Administration (FDA) has approved mirdametinib (Gomekli, SpringWorks Therapeutics, Inc.) for certain adult and pediatric patients with neurofibromatosis type 1 (NF1).

Specifically, the kinase inhibitor was approved for adults and children aged ≥ 2 years who have NF1 with symptomatic plexiform neurofibromas (PN) that are not amenable to complete resection, according to the FDA approval notice.

Approval of this rare pediatric disease product application, which received priority review, fast track designation, and orphan drug designation, was based on the overall response rate (ORR) as evaluated in the multicenter, single-arm, phase IIb ReNeu trial.

The trial enrolled 58 adults and 56 pediatric patients with symptomatic NF1-associated PN that could not be completely resected without risk for substantial morbidity. The confirmed ORRs were 41% and 52% in the adults and children, respectively.

Confirmed ORR was defined as the percentage of patients with a complete response — defined as disappearance of the target PN, or partial response — defined as a 20% or greater reduction in PN volume, within 2-6 months during the 24-cycle treatment phase.

Adverse reactions occurring in at least 25% of adults included rash, diarrhea, nausea, musculoskeletal pain, vomiting, and fatigue. Those occurring in at least 25% of pediatric patients were rash, diarrhea, musculoskeletal pain, abdominal pain, vomiting, headache, paronychia, left ventricular dysfunction, and nausea. The most common grade 3/4 laboratory abnormalities were increased creatine phosphokinase in adults and children and decreased neutrophil count in children.

Mirdametinib is also known to cause ocular toxicity, including retinal vein occlusion, retinal pigment epithelial detachment, and blurred vision, the FDA noted. Treatment should be withheld or discontinued or the dosage reduced based on the severity of adverse reactions.

Additional prescribing information, including the recommended dose based on body surface area, is available at Drugs@FDA.

Sharon Worcester, MA, is an award-winning medical journalist based in Birmingham, Alabama, writing for Medscape Medical News, MDedge, and other affiliate sites. She currently covers oncology, but she has also written on a variety of other medical specialties and healthcare topics. She can be reached at [email protected] or on X @SW MedReporter.