FDA Prioritizes Review of SpringWorks' Mirdametinib for NF1-PN Treatment

SpringWorks Therapeutics, Inc., a biopharmaceutical company dedicated to rare diseases and cancer treatment, has announced that the U.S. Food and Drug Administration (FDA) accepted its New Drug Application (NDA) for mirdametinib. This investigational MEK inhibitor is intended for treating adult and pediatric patients with neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PN). The NDA was given Priority Review, with a Prescription Drug User Fee Act (PDUFA) action date set for February 28, 2025. The FDA does not plan to hold an advisory committee meeting regarding the application.

Furthermore, the European Medicines Agency (EMA) has validated the Marketing Authorization Application (MAA) for mirdametinib for the same condition. If approved, mirdametinib could become the first therapy for adult patients and a leading treatment for children with NF1-PN.

Saqib Islam, CEO of SpringWorks, stated, "These significant milestones bring us closer to delivering transformative medicine to both adults and children with NF1-PN in the U.S. and Europe. 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."

The FDA grants Priority Review to medications that promise significant improvements over existing treatments or that provide a new treatment option where none currently exists. Both the FDA and the European Commission had previously granted Orphan Drug designation for mirdametinib for treating NF1. The FDA also provided Fast Track designation for treating patients aged two years and older with NF1-PN that are causing significant morbidity and Rare Pediatric Disease designation for treating NF1.

Annette Bakker, Ph.D., CEO of the Children's Tumor Foundation (CTF), emphasized the critical need for new treatments for adults who currently have no approved therapies. "CTF is dedicated to accelerating the development of new treatments. We congratulate our long-term partner SpringWorks on this milestone and are thrilled that patients in the U.S. and Europe could soon have a new therapy available to them."

The submissions included data from the pivotal Phase 2b ReNeu trial, which evaluated mirdametinib in patients aged two years and older with NF1-PN. The trial's results, presented at the 2024 American Society of Clinical Oncology Annual Meeting, demonstrated robust objective response rates, deep and durable responses, improvement in pain, and health-related quality of life, along with a manageable safety profile. The ReNeu trial enrolled 114 patients, administering mirdametinib in a 3-week on, 1-week off dosing schedule. Primary endpoints focused on confirmed objective response rates, while secondary endpoints included safety, tolerability, duration of response, and changes in patient-reported outcomes. The trial’s treatment phase has been completed, and patients could continue treatment in an optional long-term follow-up study.

Neurofibromatosis type 1 (NF1) is a rare genetic disorder caused by loss-of-function variants in the NF1 gene. This gene encodes neurofibromin, a critical suppressor in the MAPK pathway. NF1 affects about 1 in 2,500 individuals globally and around 100,000 people in the U.S. The disorder manifests in various symptoms, including skin pigmentation, skeletal deformities, and neurological complications, often reducing life expectancy by 8 to 15 years. Approximately 30-50% of NF1 patients develop plexiform neurofibromas, which can cause severe morbidity and, in rare cases, be fatal. These tumors are often diagnosed early in life and grow rapidly during childhood. Surgical removal is difficult due to their infiltrative nature, often resulting in nerve damage. MEK inhibitors have been validated as a class of treatment for NF1-PN.

Mirdametinib is an investigational, potent, oral MEK inhibitor designed to penetrate the central nervous system. It is being developed as a monotherapy for NF1-PN and low-grade glioma (LGG), and as a combination therapy for specific metastatic solid tumors. Mirdametinib inhibits MEK1 and MEK2, key components in the MAPK pathway, which is critical in regulating cell growth and survival, playing a significant role in various cancers and rare diseases.

SpringWorks, with its precision medicine approach, aims to develop and deliver life-changing therapies for severe rare diseases and cancer. The company has a diversified pipeline, including FDA-approved OGSIVEO® (nirogacestat) for desmoid tumors, and multiple advanced clinical trials targeting solid tumors and hematological cancers.