FDA Approves Mirdametinib for Neurofibromatosis Type 1 with Symptomatic Plexiform Neurofibromas

On February 11, 2025, the Food and Drug Administration (FDA) granted approval to mirdametinib, branded as Gomekli by SpringWorks Therapeutics, Inc. This kinase inhibitor is now available for both adults and children aged two and older who suffer from neurofibromatosis type 1 (NF1) with symptomatic plexiform neurofibromas (PN) that cannot be fully removed surgically.

The decision was based on findings from the ReNeu study (NCT03962543), a comprehensive single-arm trial conducted across multiple centers. The trial involved 114 participants aged two years and older, including 58 adults and 56 children, all diagnosed with symptomatic, inoperable NF1-related PN. These specific tumors were deemed inoperable as their complete removal posed a high risk of significant morbidity due to their location, closeness to critical body structures, or high vascularity.

The core measure of the study's effectiveness was the overall response rate (ORR), which was determined by the proportion of patients achieving either a complete disappearance of the target tumor or a partial response marked by at least a 20% reduction in tumor volume. This assessment was conducted through an independent review using volumetric MRI analysis tailored to criteria specific to neurofibromatosis and schwannomatosis, with confirmation needed between 2 to 6 months within a 24-cycle treatment window. The study found that the confirmed ORR was 41% in adults, with a confidence interval of 29 to 55%, and 52% for the pediatric group, with a confidence interval of 38 to 65%.

Adult patients commonly reported side effects such as rash, diarrhea, nausea, musculoskeletal pain, vomiting, and fatigue, with an increased level of creatine phosphokinase being a notable Grade 3 or 4 laboratory abnormality. Pediatric patients experienced similar side effects, including rash, diarrhea, musculoskeletal and abdominal pain, vomiting, headache, paronychia, left ventricular dysfunction, and nausea. Significant laboratory abnormalities in children included decreased neutrophil counts and increased creatine phosphokinase levels.

In addition to these reactions, mirdametinib can lead to left ventricular dysfunction and ocular issues, such as retinal vein occlusion and blurred vision. Depending on the severity of these adverse effects, healthcare providers may need to pause treatment, adjust dosages, or discontinue use entirely. The prescribing information includes dosage recommendations based on body surface area to mitigate these risks.

The FDA's review process for mirdametinib was supported by the Assessment Aid, a voluntary tool submitted by the applicant to streamline the evaluation. This new therapeutic option was granted priority review, fast track, and orphan drug designations. Additionally, a priority review voucher was issued, recognizing its significance as a treatment for a rare pediatric condition. The FDA's expedited programs, including guidelines for serious conditions, aim to bring important treatments to patients more swiftly.

Healthcare professionals are encouraged to report any serious adverse events linked to mirdametinib or any other medical product through the FDA's MedWatch Reporting System. For specific guidance on single-patient investigational new drug applications for oncology products, professionals can reach out to the FDA's Project Facilitate team.