NICE recommends Merck's Ezmekly (mirdametinib) for children as young as two with NF1-related plexiform neurofibromas
核心洞察
NICE has issued final draft guidance recommending mirdametinib (Ezmekly) for symptomatic plexiform neurofibromas (搜索) associated with neurofibromatosis type 1 (搜索) (NF1) in patients aged two to 17.
The recommendation extends drug treatment access to children as young as two for the first time, versus the prior age-three threshold for selumetinib (Koselugo).
Clinical evidence indicates mirdametinib can reduce tumour size with outcomes at least comparable to, and potentially better than, existing options, though based on indirect comparisons.
Around 200 children and young people with a rare genetic condition that causes tumours to grow on nerves could soon gain access to a new NHS-funded treatment, after the National Institute for Health and Care Excellence (NICE) issued final draft guidance recommending mirdametinib for symptomatic plexiform neurofibromas (搜索) associated with neurofibromatosis type 1 (搜索) (NF1).
NF1 is a rare inherited condition that affects the growth of nerve tissue and can lead to tumours developing throughout the body. While these growths are non-cancerous, they can be extremely challenging to remove surgically because of their location and may cause chronic pain, mobility difficulties, muscle weakness, vision problems and significant impacts on quality of life. The condition affects around 25,000 people in the UK, of whom around 30% to 50% develop plexiform neurofibromas (搜索).
Extending access to children as young as two
The latest recommendation marks an important step forward for families, extending access to drug treatment to children aged just two years old for the first time. Until now, the only NICE-approved drug treatment for these tumours has been selumetinib (Koselugo), which was recommended in 2022 for children aged three and above. NICE accepted clinical advice that younger children are likely to experience similar benefits from treatment.
Ezmekly was the first drug to be approved for children as young as two with the genetic disorder in the UK, and the second for NF1 after AstraZeneca/MSD's MEK1/2 inhibitor Koselugo. The medicine is manufactured by Merck Serono and marketed under the brand name Ezmekly, having received approval by the MHRA last December for both children and adults.
Clinical evidence and mechanism of action
Clinical evidence submitted to NICE indicates that mirdametinib can reduce the size of plexiform neurofibromas (搜索) and may offer outcomes that are at least comparable to, and potentially better than, existing treatment options. Evidence also suggests the therapy could be associated with fewer side effects, although NICE noted that findings are based on indirect comparisons rather than head-to-head clinical trials.
The treatment is administered twice daily, either as a tablet or a liquid formulation, and works by blocking signalling pathways that drive tumour growth. In the phase 2b ReNeu trial, mirdametinib showed an overall response rate (ORR) of 41% in adults and 52% in children, with "deep and durable" reduction in the volume of PN lesions, as well as "clinically meaningful" improvements in pain and quality-of-life scores.
"Mirdametinib offers a much-needed new option for eligible children as young as 2 years and older, while its formulation, which can be dissolved in water, may help the youngest and those who struggle to swallow tablets," commented Prof Gareth Evans, a consultant in medical genetics at Manchester University NHS Foundation Trust.
Reimbursement and prescribing considerations
NICE approved the medicine through its cost comparison process, concluding there is sufficient evidence that it delivers patient benefit while representing value for money for routine NHS use. The final draft guidance recommends that clinicians prescribe the least expensive option for paediatric NF1 patients over three years. The list price for Ezmekly is £4,670.80 for a pack of 42 capsules, while for Koselugo it is £4,223.59 for a 10 mg 60-capsule pack and £10,560.00 for 25 mg, although both drugs are being provided to the NHS at a confidential discount.
Under the guidance, clinicians will work with children and their parents or carers to determine the most appropriate treatment option. Decisions will take into account factors including administration methods, dosing requirements and overall cost, with the least expensive suitable treatment expected to be selected. If the guidance is formally published, NHS England will be required to fund mirdametinib within 30 days where it is considered the most appropriate treatment choice.
For older NF1 patients, access will need to be sought via other routes such as named patient or compassionate use programmes, as the initial recommendation focuses on the paediatric population.
Commercial context
Ezmekly — known as Gomekli in the US — was acquired by Merck as part of its $3.9 billion takeover of SpringWorks (搜索) last year and forms part of the company's portfolio of rare tumour therapies, along with desmoid tumour therapy Ogsiveo (nirogacestat). The therapy generated sales of €207 million in the first half of this year, and some analysts have suggested that peak sales of Gomekli and Ezmekly combined could top $1 billion a year.
For NHS leaders and specialist paediatric services, the recommendation represents another important development in improving access to targeted therapies for rare diseases, while expanding treatment options for families affected by NF1.