Neurofibromatosis Type 1
Neurofibromatosis Type 1 (NF1) is a rare genetic disorder caused by mutations in the NF1 gene, and that affects both children and adults. Throughout their lifetime, about 30-50 percent of NF1 patients progress to a more severe form of the disease that results in the development of plexiform neurofibromas (PN), which are progressive peripheral nerve sheath tumors that can cause severe pain, disfigurement, debilitating loss of range of motion, and can significantly shortened lifespan.1-3 The clinical course of NF1-PN is heterogeneous with varying manifestations and severity across patients.
It is estimated that NF1 affects 1 in 3,000 individuals worldwide, and that there are approximately 100,000 patients in the United States living with this disease.4 Symptoms typically begin in infancy and childhood. Most patients with NF1-PN are treated with surgical removal of the tumors, sometimes requiring amputation; however, surgery has variable success rates and a high rate of recurrence because of the aggressive nature of these tumors.5 There are no therapies currently approved for the treatment of NF1- PN.
Our Investigational Therapy
Mirdametinib is an investigational oral, small molecule, MEK1 and MEK2 inhibitor that has been tested in Phase 1 and Phase 2 clinical trials. In November 2018, the FDA granted Orphan Drug designation for mirdametinib for the treatment of NF1, and in May 2019, the FDA granted Fast Track designation for mirdametinib for the treatment of patients ≥ 2 years of age with NF1-associated inoperable plexiform neurofibromas that are progressing or causing significant morbidity.
SpringWorks is preparing to initiate a Phase 2b study of mirdametinib in patients with NF1-PN.
The mission of Children’s Tumor Foundation’s is to drive research, expand knowledge, and advance care for the NF community. The foundation has a noble vision to end NF and celebrated their 40th anniversary of fighting NF in 2018.
1 Plotkin, S. R., Bredella, M. A., Cai, W., Kassarjian, A., Harris, G. J., Esparza, S., . . . Mautner, V. F. (2012). Quantitative Assessment of Whole-Body Tumor Burden in Adult Patients with Neurofibromatosis. PLoS ONE, 7(4). doi:10.1371/journal.pone.0035711.
2 Rasmussen, S.A., & Friedman, J.M. (2000). NF1 Gene and Neurofibromatosis 1. Am J Epidemiol. 2000 Jan 1;151(1):33-40.
3 Prada, C. E., Rangwala, F. A., Martin, L. J., Lovell, A. M., Saal, H. M., Schorry, E. K., & Hopkin, R. J. (2012). Pediatric Plexiform Neurofibromas: Impact on Morbidity and Mortality in Neurofibromatosis Type 1. J Pediatr,160(3), 461-467. doi:10.1016/j.jpeds.2011.08.051.
4 Ferner, R.E. (2007). Neurofibromatosis 1 and neurofibromatosis 2: a twenty first century perspective. Lancet Neurol: 6, 340-51. doi:10.1016/S1474-4422(07)70075-3.
5 Needle, M. N., Cnaan, A., Dattilo, J., Chatten, J., Phillips, P. C., Shochat, S., . . . Molloy, P. T. (1997). Prognostic signs in the surgical management of plexiform neurofibroma: The Children’s Hospital of Philadelphia experience, 1974-1994. J Pediatr, 131(5), 678-682. doi:10.1016/s0022-3476(97)70092-1.