Irish Drug Ezmekly Gets EU Nod for Plexiform Neurofibromas

At its May 2025 meeting, the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) gave a conditional marketing authorization for mirdametinib (Ezmekly, Springworks Therapeutics Ireland Limited) for the treatment of plexiform neurofibromas (PN) in adults and children from 2 years of age with neurofibromatosis type 1 (NF1).

Plexiform neurofibroma is a genetic condition that manifests with irregular, thick, ill-defined tumors of the peripheral nerve sheaths. Most are benign, but some can change into cancerous tissue.

The CHMP grants conditional marketing authorization to a medicinal product when it can fulfil an unmet medical need and the benefit to public health of immediate availability outweighs the risk inherent in the fact that additional data are still required.

It was based on the findings of the ReNeu trial: an open-label, multicenter, pivotal, phase IIb trial of mirdametinib in adults aged 18 and older (n = 58) and children aged 2-17 years (n = 56), with NF1-PN causing significant morbidities.

Patients received mirdametinib capsules or tablets for oral suspension in 3 weeks on/1 week off, 28-day cycles. Twenty-four of 58 adults (41%) and 29 of 56 children (52%) had a blinded independent central review confirmed objective response during the 24-cycle treatment phase. In addition, two adults and one child had confirmed responses during long-term follow-up. The median target plexiform neurofibroma volumetric best response was -41% in adults and -42% in children. 

Both cohorts reported significant and clinically meaningful improvement in patient- or parent proxy-reported outcome measures of worst tumor pain severity, pain interference, and health-related quality of life that began early and were sustained during treatment. 

The researchers said that mirdametinib treatment was well-tolerated in adults and children with the most commonly reported treatment-related adverse events being dermatitis acneiform, diarrhea, and nausea in adults and dermatitis acneiform, diarrhea, and paronychia in children.

Treatment Provides Durable Responses

The active substance of Ezmekly, mirdametinib, is a selective, non-competitive mitogen-activated protein kinase 1 and 2 (MEK 1/2) inhibitor. By inhibiting MEK, mirdametinib blocks the proliferation and survival of tumor cells in which the rapidly accelerated fibrosarcoma‑MEK-extracellular related kinase pathway is activated.

In granting the authorization, the CHMP said that the benefits of Ezmekly were its ability to provide durable responses: reduction of the volume of PN in adults and children from 2 years of age with NF1-associated symptomatic, inoperable PN.

Ezmekly will be available as 1 mg and 2 mg hard capsules and 1 mg dispersible tablets as monotherapy for the treatment of symptomatic, inoperable PN in pediatric and adult patients with NF1 aged 2 years and older. 

Ezmekly was designated as an orphan medicine during its development for use against a rare, life-threatening, or chronically debilitating condition or, for economic reasons, would have been unlikely to have been developed without incentives. The EMA said that it would now review the information available to-date to determine if the orphan designation can be maintained.

Rob Hicks is a retired National Health Service doctor. A well-known TV and radio broadcaster, he has written several books and has regularly contributed to national newspapers, magazines, and online publications. He is based in the United Kingdom.