The National Institute for Health and Care Excellence (NICE) has recommended mirdametinib (Ezmekly, Merck Serono) as an option for children and young people aged 2-17 years with symptomatic, inoperable plexiform neurofibromas associated with neurofibromatosis type 1 (NF1). Around 200 patients are expected to benefit.

This marks the first time children this young have had access to a non-surgical drug treatment for the condition. Until now, the only other drug treatment for these tumours, selumetinib, has been recommended for children aged 3 years or older.

NF1 is a rare genetic condition affecting how nerve tissue develops. The resulting tumours are non-cancerous, but their location can make surgical removal difficult or impossible, and they can cause pain, weakness, movement problems, and sight loss.

Mirdametinib is the second targeted therapy available for the condition, alongside selumetinib. Both drugs are MEK inhibitors, and NICE said indirect comparisons suggest mirdametinib is likely to have a similar overall treatment effect. The committee also accepted clinical advice that children aged 2 are likely to benefit in a similar way to older children.

Tumour Shrinkage and Quality-of-Life Gains 

The recommendation was supported by findings from the phase 2b ReNeu trial, described as the largest multicentre study of NF1-associated plexiform neurofibromas reported to date. The study included 58 adults and 56 children with symptomatic, inoperable tumours.

Among the paediatric participants, 29 of 56 children (52%) achieved a confirmed objective response during the 24-cycle treatment period, defined as a reduction of at least 20% in target tumour volume. The median best percentage reduction in target tumour volume was 42%, with reductions of up to 91% reported in some patients. All confirmed responses remained durable at the data cut-off, with 76% sustained for at least 12 months.

Treatment was also associated with improvements in patient- and parent-reported outcomes, including reductions in worst tumour pain severity and pain interference, alongside improved health-related quality of life. These benefits emerged early and were sustained throughout the study period.

Manageable Safety Profile and Dosing 

Mirdametinib showed a manageable safety profile in the trial. Nearly all children (95%) had treatment-related adverse events, most of which were grade 1 or 2; the most common were dermatitis acneiform (43%), diarrhoea (38%), paronychia (30%), nausea (21%), decreased ejection fraction (20%), and increased blood creatinine phosphokinase (20%).

Dose interruptions were required in 30% of children, dose reductions in 12%, and 9% discontinued treatment because of adverse events. No child experienced symptomatic ejection fraction decline, retinal vein occlusion, or a serious treatment-related adverse event.

Mirdametinib is taken twice a day and is available as capsules and tablets for oral suspension, which may be helpful for children who have difficulty swallowing. The oral suspension was well accepted, with median scores of 5 out of 5 for willingness to take it and ease of swallowing.

Prescribing Guidance and NHS Access 

NICE advises clinicians to use the least expensive suitable treatment after discussing the advantages and disadvantages of available options with patients and their families. This includes consideration of mirdametinib and selumetinib, the latter for children and young people aged 3 years or older, as well as administration costs, dosage, price per dose, and commercial arrangements.

NICE recommended mirdametinib through its cost-comparison process, concluding that there is enough evidence that it benefits patients and offers value for money for routine NHS use. NHS England and integrated care boards are required to secure funding within 30 days of final guidance publication if the treatment is considered the most suitable option. The manufacturer has agreed to a simple discount patient access scheme providing the treatment to the NHS at a confidential discount.