America’s Food and Drug Administration (FDA) has approved Gomekli as the first drug to treat neurofibromatosis type 1 (NF1) in adults and children. NF1 causes nerve tumours and can cause hearing loss.
In a trial, the drug led to disappearance or reduction of tumours that grow in tissue around nerves (plexiform neurofibroma), in half of those treated.
Neurofibromatosis type 2 (NF2) is more usually associated with hearing loss since most people with it develop tumours along the nerves responsible for hearing and balance causing hearing loss, tinnitus and balance problems.
But NF1 has also been found to lead to hearing loss.
On 11 February 2025, the FDA approved the kinase inhibitor Gomekli (mirdametinib) from SpringWorks Therapeutics for adult and paediatric patients aged two and older with NF1 who had symptomatic plexiform neurofibromas (PN) not amenable to complete resection.
Efficacy was evaluated in a trial of 114 patients aged two and over with symptomatic, inoperable NF1-associated PN that was causing significant morbidity.
Inoperable PN was defined as plexiform neurofibromas that could not be completely surgically removed without risk for substantial morbidity due to encasement or close proximity to vital structures, invasiveness, or high vascularity.
The major efficacy outcome was confirmed overall response rate, defined as the percentage of patients with complete response (disappearance of the target PN) or partial response (≥20% reduction in PN volume).
About 41% of adults and 52% of children treated achieved disappearance or reduction in tumour volumes within two to six months during the 24-cycle treatment phase.
The most common adverse reactions in adults were rash, diarrhoea, nausea, musculoskeletal pain, vomiting, and fatigue. The most common Grade 3 or 4 laboratory abnormality was increased creatine phosphokinase.
The most common adverse reactions in paediatric patients were rash, diarrhoea, musculoskeletal pain, abdominal pain, vomiting, headache, paronychia, left ventricular dysfunction, and nausea. The most common Grade 3 or 4 laboratory abnormalities were decreased neutrophil count and increased creatine phosphokinase.
The FDA said mirdametinib could cause left ventricular dysfunction and ocular toxicity including retinal vein occlusion, retinal pigment epithelial detachment and blurred vision. Based on the severity of adverse reactions, mirdametinib should be withheld, dosage reduced or permanently discontinued, it said.
A spokesperson for the Therapeutic Goods Administration (TGA) in Australia told HPA the TGA had “neither approved nor received an application to register Gomekli (mirdametinib) for neurofibromatosis type 1 in the Australian Register of Therapeutic Goods (ARTG)”.
High rates of APD
NF1 (also known as von Recklinghausen disease) affects an estimated one in 3,000 people in Australia, according to the Murdoch Children’s Research Institute (MCRI). It said about 10,000 Australians are currently living with NF1.
The institute said children with the rare genetic disorder also have high rates of auditory processing disorder (APD).
It is investigating assistive listening devices which emphasise a speaker’s voice over background noise in children with NF1 and APD.
Associate Professor Jonathan Payne, co-lead of the MCRI’s Brain and Mind Research Group, is trialling the device in collaboration with Professor Gary Rance, The University of Melbourne’s Graeme Clark Chair in Audiology and Speech Science, Audiology and Speech Pathology.
Almost half of children with NF1 have impaired auditory processing, meaning they have considerable difficulty understanding speech in noisy environments, such as a classroom, the MCRI said.
It said its pivotal trial of a remote microphone listening device should substantially change treatment for many children with NF1 who experience impaired hearing nationwide and globally.
“Severe hearing problems disrupt communication and academic progress. This device helps children discriminate a teacher’s voice from background noise, could have immediate benefits at school and may improve academic achievement,” the institute said.
