Mirdametinib

Table of contents

• What is mirdametinib?
• How does mirdametinib work?
• Which conditions is it used or studied for?
• How is mirdametinib given?
• What do the clinical trials show?
• What side effects are known?

What is mirdametinib?

Mirdametinib is a small-molecule kinase inhibitor, a type of targeted therapy that blocks specific enzymes involved in cell growth. It is the active substance in two authorised medicines: Ezmekly in the European Union and Gomekli in the United States.^[3][2] The substance is a chemically synthesised compound and is classified as an orphan medicine, meaning it was developed for a rare disease.^[1][3] In the EU, Ezmekly received orphan designation on 25 July 2019.^[3] Mirdametinib is also available as a paediatric formulation, which makes it suitable for use in children.^[1]

How does mirdametinib work?

Mirdametinib works by blocking a protein called MEK, specifically MEK1 and MEK2.^[3][2] MEK is part of a signalling pathway inside cells that controls growth and survival. In people with neurofibromatosis type 1, this pathway is overactive because of mutations in the NF1 gene, which normally produces a protein called neurofibromin that keeps the pathway in check.^[2] When MEK is overactive, cells grow out of control and form plexiform neurofibromas along nerves. By inhibiting MEK, mirdametinib helps slow this growth and shrink the tumours.^[3] In laboratory studies, mirdametinib reduced tumour volume and cell proliferation in a mouse model of NF1.^[2]

Which conditions is it used or studied for?

• Neurofibromatosis type 1 (NF1) — a rare genetic disorder that causes benign tumours to grow on nerves throughout the body.^[4]
• Plexiform neurofibromas (PNs) — tumours that grow along the peripheral nerve sheath in people with NF1, causing pain, weakness, disfigurement, and functional impairment.^[2]
• NF1-associated plexiform neurofibromas in infants and toddlers — the ongoing Phase 1 trial studies children under 24 months of age who have symptomatic PNs or asymptomatic PNs in high-risk locations.^[1]

How is mirdametinib given?

Mirdametinib is taken by mouth. The authorised medicines are available as capsules and as dispersible tablets that can be swallowed whole or dissolved in water.^[3][4] The usual schedule in the product information is twice daily, every 12 hours, for 3 weeks followed by 1 week without the medicine, repeated in cycles.^[3] In the ongoing Phase 1 trial in infants and toddlers, mirdametinib is given as an 8 mg dispersible tablet for oral use.^[1]

What do the clinical trials show?

One Phase 1 trial of mirdametinib is currently authorised in the EU. The trial, with EU CT number 2025-522000-24-00, will enrol 8 infants and toddlers under 24 months of age with NF1-associated plexiform neurofibromas who are symptomatic or have disease in a high-risk location.^[1] The main purpose is to evaluate safety, tolerability, and pharmacokinetics — how the drug is absorbed, distributed, and cleared from the body.^[1] Key safety measures include the incidence of treatment-emergent adverse events (TEAEs), changes in laboratory values, vital signs, physical examination findings, electrocardiograms (ECGs), echocardiograms (ECHO), and eye examinations. Adverse events will be graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.^[1] Pharmacokinetic parameters measured include Cmin (the lowest drug concentration in the blood), Cmax (the highest concentration), and AUC (the total drug exposure over time).^[1] Earlier clinical research includes the Phase 2b ReNeu trial, which enrolled 58 adults and 56 children aged 2 years and older with NF1-PN. In that trial, the objective response rate (ORR) — the proportion of participants whose tumours shrank by a predefined amount — was 41% in adults and 52% in children.^[2]

What side effects are known?

MedlinePlus lists the side effects of mirdametinib, noting that patients should tell their doctor how they are feeling during treatment because dose adjustments may be needed.^[4] The EMA overview states that treatment continues until the disease worsens or side effects become unacceptable.^[3] The FDA approval was based on a Phase 2b trial showing a manageable safety profile, though specific side effect rates are not detailed in the provided sources.^[2]