Dr Blanco on the Conditional EU Approval of Mirdametinib for NF1-Associated PNs

“For Europeans, this is a great achievement because…we had no treatment for adult patients with NF1‑associated PNs. In the context of NF1, there are a lot of adult patients with symptomatic PNs where [there was] no possibility to offer anything.”

Ignacio Blanco, MD, PhD, director of the Catalan Reference Center for Neurofibromatosis in Barcelona, Spain, discussed the significance of the European Commission’s conditional marketing authorization of mirdametinib (Ezmekly) for the treatment of symptomatic, inoperable plexiform neurofibromas (PNs) in adult and pediatric patients 2 years of age and older with neurofibromatosis type 1 (NF1).

PNs are complex, often debilitating tumors that arise along peripheral nerves in some patients with NF1; these PNs can cause pain, functional impairment, and disfigurement. Blanco noted that until now, no approved medical therapy existed for adult patients with symptomatic, unresectable PNs. Surgery remains the preferred approach for operable tumors, but many lesions cannot be removed safely because of their size, location, or risk of neurologic injury, he said. Moreover, these tumors do not respond to chemotherapy, and radiotherapy offers no clinical benefit.

The approval was supported by findings from the phase 2b ReNeu trial (NCT03962543), which evaluated the efficacy and safety of mirdametinib in patients with inoperable NF1‑associated PNs. This study also supported the February 2025 FDA approval in this indication. ReNeu met its primary end point, with adult patients (n = 58) achieving a confirmed objective response rate (ORR) of 41% (n = 24), as determined by blinded independent central review. Pediatric patients (n = 56) experienced an ORR of 52%.

The median best percentage change in target lesion size was –41% (range, –90% to 13%) in adults and –42% (range, –91% to 48%) in pediatric patients. These radiographic responses were frequently accompanied by improvements in pain and functional outcomes, representing meaningful clinical benefit for patients with otherwise limited treatment options.

Blanco emphasized that optimal integration of mirdametinib into clinical practice will require careful patient selection. The treatment is intended for patients with symptomatic PNs that are not surgically resectable; if the tumor is operable, surgery remains the standard approach. Early identification of eligible patients through multidisciplinary evaluation will be essential to ensuring appropriate use.

As an oral MEK inhibitor, mirdametinib targets aberrant RAS/MAPK pathway signaling, a central driver of tumorigenesis in NF1. Blanco noted that, as a conditional authorization, ongoing data collection will be required to confirm long‑term benefit and safety, with post‑authorization studies expected to further define the durability of response and the treatment’s role across age groups and clinical contexts.