On February 11, 2025, the Food and Drug Administration approved mirdametinib, a kinase inhibitor, for adult and paediatric patients 2 years of age and older with neurofibromatosis type 1 (NF1) who have symptomatic plexiform neurofibromas (PN) not amenable to complete resection.

Full prescribing information for mirdametinib will be posted on Drugs@FDA.

Efficacy and Safety

Efficacy was evaluated in ReNeu (NCT03962543), a multicenter, single-arm trial in 114 patients ≥2 years of age (58 adults, 56 paediatric patients) with symptomatic, inoperable NF1-associated PN causing significant morbidity. An inoperable PN was defined as a PN that could not be completely surgically removed without risk for substantial morbidity due to encasement or close proximity to vital structures, invasiveness, or high vascularity.

The major efficacy outcome measure was confirmed overall response rate (ORR), defined as the percentage of patients with complete response (disappearance of the target PN) or partial response (≥20% reduction in PN volume). Responses were assessed by blinded independent central review using volumetric MRI analysis per Response Evaluation in Neurofibromatosis and Schwannomatosis criteria, modified to require confirmation of responses within 2 to 6 months during the 24-cycle treatment phase. Confirmed ORR was 41% for adults (95% CI: 29, 55) and 52% in the paediatric cohort (95% CI: 38, 65).

The most common adverse reactions (>25%) in adult patients were rash, diarrhoea, nausea, musculoskeletal pain, vomiting, and fatigue. The most common Grade 3 or 4 laboratory abnormality (>2%) was increased creatine phosphokinase.

The most common adverse reactions (>25%) in paediatric patients were rash, diarrhoea, musculoskeletal pain, abdominal pain, vomiting, headache, paronychia, left ventricular dysfunction, and nausea. The most common Grade 3 or 4 laboratory abnormalities (>2%) were decreased neutrophil count and increased creatine phosphokinase.

Mirdametinib can also cause left ventricular dysfunction and ocular toxicity including retinal vein occlusion, retinal pigment epithelial detachment and blurred vision. Mirdametinib should be withheld, dosage reduced or permanently discontinued based on the severity of adverse reactions.

See the prescribing information for the recommended dose based on body surface area.

Expedited Programs

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. submission from the applicant to facilitate the FDA’s assessment.

This application was granted priority review, fast track designation, and orphan drug designation. A priority review voucher was issued for this rare paediatric disease product application. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitateat240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.

Source: FDA