FDA Grants Priority Review to Mirdametinib for Neurofibromatosis Type 1-Associated Plexiform Neurofibromas

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The FDA has granted Priority Review to SpringWorks Therapeutics’ New Drug Application (NDA) for mirdametinib, an investigational MEK inhibitor for the treatment of neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PN) in both adults in children. The NDA included data from the Phase IIb ReNeu trial, which evaluated mirdametinib in patients over two years of age with NF1-associated plexiform neurofibromas (PN) causing significant morbidity.¹

“These significant milestones bring us closer to our goal of delivering a transformative medicine to both adults and children with NF1-PN in the U.S. and Europe,” said Saqib Islam, CEO, SpringWorks, in a press release. “People living with NF1-PN are in need of new advances and we look forward to working with the FDA and EMA during their review processes as we prepare to bring our second medicine to patients suffering from devastating diseases.”

The ongoing multi-center, open-label ReNeu trial is evaluating the efficacy, safety, and tolerability of mirdametinib in patients ≥ 2 years of age with an inoperable NF1-associated PN causing significant morbidity. As part of the study, 114 patients received mirdametinib at a dose of 2 mg/m2 twice daily (maximum dose of 4 mg twice daily) without regard to food.

The treatment was administered orally in a three-week on, one-week off dosing schedule as either a capsule or dispersible tablet. The primary endpoint of the study is confirmed objective response rate (ORR) assessed by proportion of patients with ≥ 20% reduction in target tumor volume on consecutive scans during the 24-cycle treatment phase, as measured by MRI and assessed by blinded independent central review. The secondary endpoints of the study include safety and tolerability, duration of response, and changes in patient-reported outcomes from baseline to cycle 13.

Results of the trial, which were presented at the 2024 American Society of Clinical Oncology Annual Meeting, found that mirdametinib treatment resulted in a robust ORR confirmed by blinded independent central review, deep and durable responses, improvement in pain and health-related quality of life, as well as a manageable safety profile across both the adult and pediatric cohorts, according to SpringWorks.¹

According to the European Medical Journal, anywhere from 30% to 50% of patients with NF1 develop NF1-associated PN. As a result, it carries a lifelong risk for malignancy of 8% to 13%.²

“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,” said Annette Bakker, PhD, CEO, Children’s Tumor Foundation (CTF), board chair, CTF Europe, in the press release. “CTF is dedicated to deploying its time, talent and funding towards accelerating the development of new treatments. We congratulate our long-term partner SpringWorks on this important milestone and we are thrilled that patients in the United States and Europe could soon have a new therapy available to them.”

Previously, Mirdametinib was granted an Orphan Drug designation by the FDA and European Commission, as well as Fast Track and rare pediatric disease designations by the FDA. The FDA has set a Prescription Drug User Fee Act of Feb. 28, 2025. However, there are currently no plans to hold an advisory committee meeting to discuss the application.

References

1. FDA Grants Priority Review to SpringWorks Therapeutics’ New Drug Application for Mirdametinib for the Treatment of Adults and Children with NF1-PN. SrpingWorks Therapeutics. August 28, 2024. Accessed August 29, 2024. https://ir.springworkstx.com/news-releases/news-release-details/fda-grants-priority-review-springworks-therapeutics-new-drug

2. Neurofibromatosis Type 1: Burden of Disease in Patients with Plexiform Neurofibromas. EMJ. December 9, 2021. Accessed August 29, 2024. https://www.emjreviews.com/oncology/symposium/neurofibromatosis-type-1-burden-of-disease-in-patients-with-plexiform-neurofibromas-j190421/#:~:text=Summary,associated%20plexiform%20neurofibromas%20(PN).