Significance of Recently Approved Mirdametinib for NF1-Associated Plexiform Neurofibromas: P. Leia Nghiemphu, MD

WATCH TIME: 2 minutes

"Now we actually have a treatment option that is targeted toward tumor... it’s really treating the cause of the pain too."

Neurofibromatosis type 1 (NF1) is a genetic disorder that primarily affects the nervous system and skin, characterized by the growth of benign tumors along nerves and other clinical features. It is caused by mutations in the NF1 gene, which provides instructions for making neurofibromin, a protein that regulates cell growth. Mutations in this gene lead to uncontrolled cell growth, resulting in tumor formation.

Earlier this month, the FDA granted approval to SpringWorks Therapeutics’ agent mirdametinib (Gomekli) as a new treatment for adult and pediatric patients with NF1 who have symptomatic plexiform neurofibromas (PN) that are not amenable to complete surgical resection. The approval was based on findings from the phase 2 ReNeu trial (NCT039662543), an open-label study of 58 adult patients and 56 pediatric patients who received mirdametinib at 2 mg/m2 twice daily on a 3-week-on, 1-week-off schedule. The study’s primary end point, confirmed overall response rate (ORR), defined as at least a 20% reduction in target tumor volume, was observed in 41% of adult patients and 52% of pediatric patients.

To gain greater insights on how this treatment will impact the NF1 community, NeurologyLive^® turned to P. Leia Nghiemphu, MD, a neurooncologist at the University of California Los Angeles (UCLA). Ngiemphu, who also directs the neuro-oncology clinical service and the neuro-oncology fellowship program, provided commentary on the mechanism of the therapy as a MEK inhibitor, and which patients may respond best to treatment. She noted the drug is particularly important for individuals with growing or symptomatic PF, which often cause neuropathic pain, especially in adults. Overall, she spoke about how this new treatment provides a targeted therapeutic approach, offering potential tumor shrinkage and pain relief, marking a major advance in NF1 care.

REFERENCES
1. FDA approves mirdametinib for adult and pediatric patients with neurofibromatosis type 1 who have symptomatic plexiform neurofibromas not amenable to complete resection. FDA. February 11, 2025. Accessed February 11, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-mirdametinib-adult-and-pediatric-patients-neurofibromatosis-type-1-who-have-symptomatic
2. Moertel CL, Hirbe AC, Shuhaiber HH, et al. ReNeu: a pivotal phase 2b trial of mirdametinib in adults and children with neurofibromatosis type 1 (NF1)-associated symptomatic inoperable plexiform neurofibroma (PN). J Clin Oncol. 2024;42(suppl 16):3016. doi:10.1200/JCO.2024.42.16_suppl.3016