SpringWorks Submits NDA to FDA for Mirdametinib for NF1-PN

SpringWorks Therapeutics, Inc., a commercial-stage biopharmaceutical company listed on Nasdaq as SWTX, has announced the completion of a New Drug Application (NDA) submission to the U.S. Food and Drug Administration (FDA) for mirdametinib. This investigational MEK inhibitor is intended for treating pediatric and adult patients with neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PN).

CEO of SpringWorks, Saqib Islam, expressed optimism about the potential approval of mirdametinib, highlighting the promising data from the ReNeu trial that could make mirdametinib a leading therapy for NF1-PN patients in the United States. The company also plans to seek regulatory approval in the European Union later in the year.

The NDA submission features data from the pivotal Phase 2b ReNeu trial, which evaluated the efficacy and safety of mirdametinib in patients aged 2 years and older with NF1-associated PN. The ReNeu trial results, presented at the 2024 American Society of Clinical Oncology Annual Meeting, demonstrated significant objective response rates, durable responses, and improvements in pain and quality of life, with a manageable safety profile in both adult and pediatric cohorts.

The FDA and the European Commission have granted Orphan Drug designation to mirdametinib for the treatment of NF1. Additionally, the FDA has provided Fast Track designation for patients aged 2 years and older with progressing or significantly morbid NF1-PN and Rare Pediatric Disease designation for NF1.

SpringWorks plans to submit a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) in the latter half of 2024 for mirdametinib to treat both children and adults with NF1-PN.

The ReNeu trial (NCT03962543) is an ongoing, multi-center, open-label Phase 2b study that investigates the efficacy, safety, and tolerability of mirdametinib in patients aged 2 years and older with inoperable NF1-associated PN. The study enrolled 114 patients who received mirdametinib at a dose of 2 mg/m² twice daily, with a maximum dose of 4 mg twice daily, in a 3-week on, 1-week off dosing schedule. The primary endpoint was a confirmed objective response rate, defined as a 20% or greater reduction in target tumor volume, as measured by MRI and assessed by independent central review. Secondary endpoints included safety, duration of response, and changes in patient-reported outcomes through Cycle 13.

Neurofibromatosis type 1 (NF1) is a genetic disorder caused by mutations in the NF1 gene, which encodes neurofibromin, a critical suppressor of the MAPK pathway. NF1 is the most prevalent form of neurofibromatosis, with an estimated global incidence of 1 in 2,500 births and around 100,000 patients in the U.S. The disorder's clinical manifestations are diverse, affecting multiple organ systems, and patients with NF1 have a reduced life expectancy compared to the general population.

About 30-50% of NF1 patients develop plexiform neurofibromas (PN), tumors growing along the peripheral nerve sheath, leading to disfigurement, pain, and functional impairment. These tumors are typically diagnosed in childhood and can be aggressive, often presenting significant clinical challenges. Surgical removal of PN is difficult due to its infiltrative growth along nerves, which can result in permanent damage and disfigurement. MEK inhibitors have emerged as a validated treatment class for NF1-PN.

Mirdametinib is an investigational, orally administered MEK inhibitor designed to inhibit MEK1 and MEK2, key components of the MAPK pathway involved in cell growth and survival. It is under development as a monotherapy for NF1-PN and low-grade glioma, and in combination therapies for various metastatic solid tumors. While mirdametinib is investigational and its safety and efficacy have not been fully established, its development carries significant potential for treating NF1-associated conditions.

SpringWorks Therapeutics is committed to developing precision medicines for severe rare diseases and cancer, with a pipeline that includes both proprietary and collaborative programs aimed at fulfilling unmet medical needs.