FDA Assigns Review Date for Mirdametinib in Genetic Neuro-Oncology Condition

The FDA has accepted the new drug application (NDA) for mirdametinib, an investigational MEK inhibitor, to treat adult and pediatric patients with neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PN). The NDA was granted priority review and has been given a Prescription Drug User Fee Act (PDUFA) action date of Feb. 28, 2025. If approved, mirdametinib would be the first therapy for the treatment of adult patients.

Neurofibromatosis type 1 is a rare genetic condition characterized by changes in skin coloring and the growth of tumors along nerves in the skin, brain, and other parts of the body. NF1 is the most common form of neurofibromatosis, with about 100,000 patients in the United States. Plexiform neurofibromas are tumors that grow along the peripheral nerve sheath and can cause severe disfigurement, pain and functional impairment.

Developed by SpringWorks Therapeutics, mirdametinib is an oral, small molecule that is designed to inhibit MEK1 and MEK2 on the MAPK pathway. The MAPK pathway is a key signaling network that regulates cell growth and plays a central role in multiple cancers.

SpringWorks also announced that the European Medicines Agency (EMA) has validated the marketing authorization application (MAA) for mirdametinib for the same indication.

Annette Bakker, Ph.D.

“Plexiform neurofibromas may sit next to or surround vital organs and can cause serious medical complications for patients. While progress has been made, there remains a pressing need for more treatment options, particularly for adults who currently have no approved therapy,” Annette Bakker, Ph.D., CEO of the Children’s Tumor Foundation (CTF) and Board Chair of CTF Europe, said in a news release.

Both the U.S. and EMA submissions include data from the pivotal phase 2b ReNeu trial, which evaluated mirdametinib in patients 2 years of age or older with NF1-associated PN causing significant morbidity. The study enrolled 114 patients who received mirdametinib 2 mg twice daily. Mirdametinib was given in a three-week on, one-week off dosing schedule as either a capsule or dispersible tablet.

As of the data cutoff of Sept. 20, 2023, mirdametinib treatment resulted in a confirmed objective response rate (ORR) of 41% in adults and 52% objective response rate in children. Median best change in tumor volume from baseline was -41% in adults and -42% in children. The median treatment duration for both adults and children was 22 months.

Most adverse events were grade 1 or 2. Among all study participants, 21% of adults and 9% of children discontinued the study due to treatment-related adverse events, and dose reductions due to TRAEs were 17% in adults and 12% in children.

Results were presented in an oral presentation at the 2024 American Society of Clinical Oncology Annual Meeting.

SpringWorks is also developing mirdametinib to treat pediatric patients with low-grade gliomas. Initial data from a phase 1/2 trial were presented at the ISPNO 2024 meeting. Results from 23 patients enrolled in the phase 1 portion suggested that mirdametinib has encouraging clinical activity in patients with recurrent/progressive pLGG across a variety of MAPK pathway aberrations. The phase 2 portion of the study is ongoing and recruiting patients.