On 22 May 2025, the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) recommended granting a conditional marketing authorisation for mirdametinib (brand name: Ezmekly). This targeted therapy is intended for adults and children aged 2 years and older with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas. The recommendation highlights the potential of mirdametinib to address an unmet medical need in this rare disease population.

Treatment Target and Mechanism

Mirdametinib is a selective, non-competitive inhibitor of MEK1 and MEK2, components of the RAF-MEK-ERK signalling pathway, which plays a central role in the growth and survival of tumour cells. In NF1 patients, this pathway is often abnormally activated, contributing to the development of plexiform neurofibromas. By blocking MEK, mirdametinib helps reduce tumour volume and limit disease progression. It will be available as 1 mg and 2 mg hard capsules and 1 mg dispersible tablets under the brand name Ezmekly.

Clinical Benefits and Trial Results

The clinical benefit of Ezmekly was demonstrated in a single-arm study, where it showed durable responses—mainly tumour shrinkage—in NF1 patients with symptomatic, inoperable plexiform neurofibromas. This outcome was observed in both adults and children starting from age 2, providing hope for a patient group that previously lacked effective treatment options.

Side Effects and Safety Profile

In adult patients, common side effects reported with Ezmekly include acneiform dermatitis, diarrhoea, nausea, increased creatine phosphokinase, musculoskeletal pain, vomiting, and fatigue. In children, similar side effects were observed, with abdominal pain and headache also noted. These findings reflect a generally manageable safety profile, although continued monitoring is necessary as more data become available.

Regulatory Status and Orphan Designation

Mirdametinib received an orphan drug designation during its development, acknowledging the rarity of NF1 and the lack of treatment options for its related tumours. The CHMP’s recommendation paves the way for conditional approval, meaning the product can be made available before all confirmatory clinical data are in. However, the manufacturer, SpringWorks Therapeutics Ireland Limited, will need to submit comprehensive long-term data later to confirm its efficacy and safety.

Next Steps and Access

Following this positive opinion, the European Commission is expected to issue a final decision within approximately 67 days. Once approved, full prescribing information will be published on the EMA website. As part of the conditional authorisation process, the treatment will be restricted to use by physicians experienced in managing NF1-related tumours.

This recommendation represents an important milestone for the NF1 community, potentially offering the first targeted oral therapy for children and adults with symptomatic, inoperable plexiform neurofibromas.