Drug Update · Oncology

FDA Approves Mirdametinib for NF1 PN: 41% ORR in Adults (ReNeu)

July 18, 2026

Indication

Adults and pediatric patients ≥2 years with NF1 and symptomatic plexiform neurofibromas not amenable to complete resection [7]

Approval date

February 11, 2025 (FDA) [7]

Primary efficacy (adult ORR)

41% confirmed ORR by BICR in adults (ReNeu) [1]

Primary efficacy (pediatric ORR)

52% confirmed ORR by BICR in children (ReNeu) [1]

Recommended dose

2 mg/m2 orally twice daily for first 21 days of each 28-day cycle (label) [12]

Trial

ReNeu, pivotal, phase IIb, open-label, multicenter, single-arm (58 adults, 56 children) [1][7]

Clinical Perspective

This approval affects oncologists, pediatric oncology specialists, neurologists and multidisciplinary teams caring for patients with NF1 and symptomatic plexiform neurofibromas. The ReNeu data support use of mirdametinib for patients 2 years and older with PN not amenable to complete resection, demonstrating confirmed tumor-volume responses and patient-reported symptom improvements ^[1]^[2]. Clinicians should assess baseline cardiac and ophthalmic status and monitor for adverse reactions noted in the prescribing information; dosing and monitoring guidance are available in the approved label and should be consulted prior to initiation.

Dr. Meera Pillai · Oncology

The FDA approved mirdametinib (Gomekli) for adult and pediatric patients 2 years of age and older with neurofibromatosis type 1 (NF1) who have symptomatic plexiform neurofibromas (PN) not amenable to complete resection on February 11, 2025 ^[2]. Approval was based on the single-arm ReNeu trial, in which blinded independent central review confirmed an overall response rate (ORR) of 41% in adults and 52% in children, defined as ≥20% volumetric PN reduction during the 24-cycle treatment phase ^[1]^[2].

Clinical Context

Mirdametinib is a small-molecule kinase inhibitor that targets mitogen-activated protein kinase kinases 1 and 2 (MEK1/2) ^[3]. It is developed and marketed by SpringWorks Therapeutics as Gomekli. The FDA approval covers both adult and pediatric patients 2 years and older with symptomatic NF1-associated plexiform neurofibromas that cannot be completely resected because of proximity to vital structures, invasiveness, or vascularity ^[2]. The approval provides an FDA-authorized systemic MEK inhibitor option for NF1-PN across pediatric and adult age groups, based on objective tumor-volume responses and associated patient-reported improvements in pain and health-related quality of life in the ReNeu trial ^[1]^[2]^[3].

Key Findings

The ReNeu trial, an open-label, multicenter, pivotal phase IIb study, enrolled 58 adults and 56 children with symptomatic, inoperable NF1-associated PN and used volumetric MRI assessed by blinded independent central review (BICR) to determine confirmed ORR (≥20% reduction in target PN volume on consecutive scans) during a 24-cycle treatment phase ^[1].
ReNeu results: 24 of 58 adults (41%) had a BICR-confirmed objective response and 29 of 56 children (52%) had a BICR-confirmed objective response during the 24-cycle treatment phase; additional confirmed responses occurred during long-term follow-up (two adults, one child) ^[1].
Median target PN volumetric best response was -41% (range -90 to 13) in adults and -42% (range -91 to 48) in children; patient- or proxy-reported measures showed early and sustained improvement in worst tumor pain severity, pain interference, and health-related quality of life during treatment ^[1].

Safety & Tolerability

Mirdametinib adverse events reported in the ReNeu trial included the following treatment-related adverse events explicitly named in the trial report and prescribing information: dermatitis acneiform, diarrhea, nausea, paronychia (children), vomiting, musculoskeletal pain, fatigue, and left ventricular dysfunction. The prescribing information notes serious adverse reactions and laboratory abnormalities, including decreased neutrophil count and increased creatine phosphokinase, and documents that permanent discontinuation, dose interruptions, and dose reductions occurred for adverse reactions in both adult and pediatric cohorts ^[1]^[3].

Study Design

ReNeu was an open-label, multicenter, pivotal, phase IIb single-arm trial of mirdametinib in 114 patients aged ≥2 years (58 adults, 56 children) with symptomatic, inoperable NF1-associated plexiform neurofibromas causing significant morbidity ^[1]^[2]. The primary endpoint was confirmed ORR by blinded independent central review using volumetric MRI (≥20% reduction in target PN volume confirmed on consecutive scans during the 24-cycle treatment phase). Patients received mirdametinib in 28-day cycles with 21 days on treatment and 7 days off; dosing in the label is based on body surface area ^[1]^[3]. Approval was granted by the US Food and Drug Administration on February 11, 2025 ^[2].

FAQ

Q1 What is mirdametinib (Gomekli) approved for?

Mirdametinib (Gomekli) is approved for the treatment of adult and pediatric patients 2 years of age and older with neurofibromatosis type 1 (NF1) who have symptomatic plexiform neurofibromas (PN) not amenable to complete resection. The FDA approval was based on tumor-volume response data from the ReNeu trial showing confirmed objective responses in both adult and pediatric cohorts.

Q2 How does mirdametinib work?

Mirdametinib is an inhibitor of mitogen-activated protein kinase kinases 1 and 2 (MEK1/2), which are upstream regulators of the ERK pathway. Inhibition of MEK1/2 reduces downstream ERK phosphorylation; preclinical models of NF1 have shown that MEK inhibition can reduce neurofibroma proliferation and volume, and the approval was supported by clinical tumor-volume reductions assessed by blinded independent central review in the ReNeu study.

Q3 What is the recommended dose of mirdametinib (Gomekli)?

The recommended dosage of Gomekli is 2 mg/m2 administered orally twice daily for the first 21 days of each 28-day cycle, with dosing continued until disease progression or unacceptable toxicity; the maximum dose is 4 mg twice daily and the approved product is available as capsules and tablets for oral suspension. Dosing in the label is based on body surface area and includes instructions for tablet dispersion for patients unable to swallow capsules or tablets whole. Clinicians should consult current prescribing information for complete dosing guidance.

Q4 What are the most common side effects of mirdametinib?

The ReNeu trial and prescribing information list treatment-related adverse events including dermatitis acneiform (rash), diarrhea, nausea, vomiting, musculoskeletal pain, fatigue, paronychia (noted in pediatric patients), and left ventricular dysfunction; laboratory abnormalities reported include decreased neutrophil count and increased creatine phosphokinase. Serious adverse reactions, treatment interruptions, dose reductions, and permanent discontinuations occurred in both adult and pediatric cohorts; clinicians should follow label guidance for baseline assessments and monitoring.

Clinicians should consult current prescribing information for complete dosing guidance.

FDA Approves Mirdametinib for NF1 PN: 41% ORR in Adults (ReNeu)

FDA Approves Mirdametinib for NF1 PN: 41% ORR in Adults (ReNeu)

Clinical Perspective

Clinical Context

Key Findings

Safety & Tolerability

Study Design

FAQ

References

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