FDA approves mirdametinib for adult and pediatric patients with neurofibromatosis type 1 who have symptomatic plexiform neurofibromas not amenable to complete resection
Regulatory approval: On Feb 11, 2025, the FDA approved mirdametinib (Gomekli; SpringWorks Therapeutics), a kinase inhibitor, for adults and pediatric patients aged ≥2 years with neurofibromatosis type 1 (NF1) who have symptomatic plexiform neurofibromas (PN) not amenable to complete resection. Approval was supported by the single-arm ReNeu trial (NCT03962543), which reported confirmed ORR of 41% in adults and 52% in pediatric patients by blinded central review using volumetric MRI.
FDA approval: mirdametinib for NF1-associated symptomatic, inoperable PN
Type: Regulatory approval
Date: 2025-02-11
Agency: FDA
The FDA approved mirdametinib (Gomekli; SpringWorks Therapeutics, Inc.), a kinase inhibitor, for adult and pediatric patients aged ≥2 years with neurofibromatosis type 1 (NF1) who have symptomatic plexiform neurofibromas (PN) not amenable to complete resection.
Supporting evidence (ReNeu; NCT03962543)
Efficacy and safety were evaluated in ReNeu, a multicenter, single-arm trial enrolling 114 patients ≥2 years (58 adults; 56 pediatric) with symptomatic, inoperable NF1-associated PN causing significant morbidity. “Inoperable” was defined as PN not completely resectable without substantial morbidity due to proximity/encasement of vital structures, invasiveness, or high vascularity.
Primary efficacy endpoint: confirmed overall response rate (ORR) (CR = disappearance of target PN; PR = ≥20% reduction in PN volume), assessed by blinded independent central review using volumetric MRI per modified REiNS criteria (confirmation within 2–6 months during the 24-cycle phase).
Confirmed ORR:
- Adults: 41% (95% CI, 29–55)
- Pediatric: 52% (95% CI, 38–65)
Safety highlights (as reported)
Common adverse reactions (>25%) included rash, diarrhea, nausea, and musculoskeletal pain (with age-specific differences). Reported risks included left ventricular dysfunction and ocular toxicity (e.g., retinal vein occlusion, retinal pigment epithelial detachment, blurred vision).
The application received priority review, fast track, and orphan drug designation; a priority review voucher was issued for this rare pediatric disease product application.