EZMEKLY (mirdametinib) - Neurofibromatosis type 1 (NF1) aged 2 years and above

Opinions on drugs - Posted on Jan 16 2026

Reason for request

Inclusion on list

Summary of opinion

Favourable opinion for reimbursement in the treatment of symptomatic, inoperable plexiform neurofibromas (PN) in paediatric patients with neurofibromatosis type 1 (NF1) aged 2 years and above.

Clinical Benefit

Substantial	That the clinical benefit of EZMEKLY (mirdametinib) 1 mg hard capsules and dispersible tablets and 2 mg hard capsules is substantial in the indication for the treatment of symptomatic, inoperable plexiform neurofibromas (PN) in paediatric patients with neurofibromatosis type 1 (NF1) aged 2 years and above.
Low	The clinical benefit of EZMEKLY 1 mg and 2 mg (mirdametinib) hard capsules and EZMEKLY 1 mg (mirdametinib) dispersible tablets is low in the indication for the treatment of symptomatic, inoperable plexiform neurofibromas (PN) in adult patients with neurofibromatosis type 1 (NF1).

Clinical Added Value

minor

Considering:

the unmet medical need in children under 3 years of age and the need in children 3 to ≤ 17 years of age only partially met by selumetinib hard capsules, a delivery form unsuitable for paediatric patients, particularly children under 6 years of age who may have difficulties swallowing hard capsules,
the benefit of a dispersible tablet form of EZMEKLY (mirdametinib), more suitable for administration in children under 6 years of age,
non-comparative data from the phase 2 MEK-NF-201 study conducted in adult patients and paediatric patients aged 2 years and above with neurofibromatosis type 1 (NF1) with symptomatic, inoperable plexiform neurofibromas (PN), treated with mirdametinib for up to 24 treatment cycles (around 22 months), suggesting objective response rates (partial responses + complete responses) of 41% (n = 24/58; CI95% [29; 55]) in the adult cohort and 52% (n = 29/56; CI95% [38; 65]) in the paediatric cohort, but without the observation of complete responses,
the absence of robust data relative to the alleviation of pain, a major symptom in this condition, and the quality of life of patients, despite this being significantly impaired in the event of bulky PN,
the safety profile of mirdametinib, marked by adverse events, in particular gastrointestinal and cutaneous, and the need for regular monitoring, particularly of cardiac and ocular function,
uncertainties concerning the long-term efficacy and safety, pending data from the extension phase of the MEK-NF-201 study and the PASS study,

the Committee deems that EZMEKLY 1 mg and 2 mg (mirdametinib) hard capsules and EZMEKLY 1 mg (mirdametinib) dispersible tablets provide a minor clinical added value (CAV IV), in the same way as KOSELUGO (selumetinib), in the care pathway for the treatment of symptomatic, inoperable plexiform neurofibromas (PN) in paediatric patients with
neurofibromatosis type 1 (NF1) aged 2 years and above.

no clinical added value

Considering:

the medical need partially met in adults by selumetinib, available since 04/09/2025 in the context of a pre-MA early access authorisation,
non-comparative data from the phase 2 MEK-NF-201 study conducted in paediatric and adult patients with neurofibromatosis type 1 (NF1) aged 2 years and above with symptomatic, inoperable plexiform neurofibromas (PN), treated with mirdametinib for up to 24 treatment cycles (around 22 months), suggesting objective response rates (partial responses + complete responses) of 41% (n = 24/58; CI95% [29; 55]) in the adult cohort and 52% (n = 29/56; CI95% [38; 65]) in the paediatric cohort, but without the observation of complete responses,
the absence of robust data relative to the alleviation of pain, a major symptom in this condition, and the quality of life of patients, despite this being significantly impaired in the event of bulky PN,
the better level of evidence provided by KOSELUGO (selumetinib), for which comparative data versus placebo are available in adults (KOMET study),
the safety profile of mirdametinib, marked by adverse events, in particular gastrointestinal and cutaneous, and the need for regular monitoring, particularly of cardiac and ocular function,
uncertainties concerning the long-term efficacy and safety, pending data from the extension phase of the MEK-NF-201 study and the PASS study,

the Committee deems that EZMEKLY 1 mg and 2 mg (mirdametinib) hard capsules and EZMEKLY 1 mg (mirdametinib) dispersible tablets provide no clinical added value (CAV V), in the care pathway for the treatment of symptomatic, inoperable plexiform neurofibromas (PN) in adult patients with neurofibromatosis type 1 (NF1).