Merck rare tumour drug Ezmekly backed for NHS use

Merck KGaA's recently approved neurofibromatosis type 1 (NF1) therapy Ezmekly has been cleared for routine NHS use in England, becoming an option for children as young as two with the rare disease.

Reimbursement authority NICE has given the go-ahead for the use of oral MEK inhibitor Ezmekly (mirdametinib) to treat symptomatic, inoperable plexiform neurofibromas (PN) associated with NF1 in patients aged two to 17, nine months after its approval by the MHRA last December for both children and adults.

NF1 is a genetic condition that causes tumours to develop on the covering of nerve cells, leading to disfigurement and other debilitating complications like pain, motor dysfunction, and malignant peripheral nerve sheath cancers. It affects around 25,000 people in the UK, of whom around 30% to 50% develop PN.

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 (selumetinib), which was recommended by NICE in 2022 for use in NF1 patients aged three and over.

NICE's final draft guidance (PDF) recommends that clinicians prescribe the least expensive option for paediatric NF1 patients over three years.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.

When NICE leaves adults out of an initial recommendation, it is often an invitation for the sponsor to submit a specific discount for the older age group. For now, older NF1 patients will have to try for access via other routes like named patient or compassionate use programmes.

"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.

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.

Ezmekly – known as Gomekli in the US – was acquired by Merck as part of its $3.9 billion takeover of SpringWorks last year and part of the company's portfolio of rare tumour therapies, along with desmoid tumour therapy Ogsiveo (nirogacestat), and generated sales of €207 million in the first half of this year.

Some analysts have suggested that peak sales of Gomekli and Ezmekly combined could top $1 billion a year.