Over their lifetime, people with neurofibromatosis type 1 (NF1), a rare genetic disorder, have a 30-50% chance of developing plexiform neurofibromas. These tumors grow on peripheral nerve sheaths throughout the body. Typically appearing in the first two decades of life and growing aggressively in early childhood, neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PN) can cause mobility issues, physical pain, and areas of skin discoloration or tissue overgrowth, impairing quality of life. In some cases, NF1-PN can become fatal.
NF1-PN can be difficult to treat. While surgery is an option, NF1-PN tumors often appear in challenging places such as the head, neck, and chest. The tumors may infiltrate surrounding tissue and are also vascularized, meaning there is a higher chance of bleeding during surgery. Koselugo is currently the only FDA-approved therapy that reduces the size of plexiform neurofibromas. However, clinical-stage biopharmaceutical company SpringWorks Therapeutics, Inc. (“SpringWorks”) is working to bring patients another option with mirdametinib. SpringWorks describes mirdametinib as an investigational small-molecule MEK inhibitor, given orally.
Outside of NF1-PN, SpringWorks is also evaluating mirdametinib as a potential therapeutic option for low-grade gliomas and other biomarker-defined metastatic solid tumors. Mirdametinib has received Orphan Drug and Rare Pediatric Disease designations from the FDA for NF1, as well as Fast Track designation for NF1-PN.
Phase 2b ReNeu Study Findings: Evaluating an NF1-PN Treatment
Recently, in a news release on Morningstar, SpringWorks shared positive topline results from the Phase 2b ReNeu study. Within the study, researchers evaluated the safety, efficacy, and tolerability of mirdametinib for both adults and children (ages 2+) living with NF1-PN. Altogether, 114 participants enrolled in this ongoing study. Participants received 2mg/m2 mirdametinib 2x daily. The reported data has a data cutoff date of September 20, 2023.
Findings from the study show that 52% and 41% of children and adults, respectively, had an objective response to treatment. An objective response encompasses those with complete responses (no more signs of the condition) or partial responses (tumor reduction, for example). A smaller subset of individuals also had an objective response during the follow-up portion of the study. Both subsets of patients saw reductions in tumor volume, with the median percentage change being between -41-42%. Patients also reported improvements in symptoms like pain and had more physical mobility and function.
While mirdametinib was both safe and well-tolerated, some individuals experienced side effects such as rashes, nausea and vomiting, and diarrhea.
More data from the study will be shared in the coming year.
