Neurofibromatosis Type 1
Neurofibromatosis Type 1, or NF1, is a rare genetic disorder caused by mutations in the NF1 gene. About 30-50 percent of NF1 patients progress to develop plexiform neurofibromas (PN), a more severe form of the disease that results in tumors growing on nerves throughout the body, which can result in severe pain, disfigurement, loss of range of motion, and shortened lifespan.1-3 The clinical course of NF1-associated 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-associated 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-associated PN.
Our Investigational Therapy
PD-0325901 is an investigational oral, small molecule, MEK1 and MEK2 inhibitor that has been tested in Phase 1 and Phase 2 clinical trials. The U.S. Food and Drug Administration (FDA) has granted Orphan Drug designation for PD-0325901 for the treatment of NF1. SpringWorks is preparing to initiate a Phase 2b study of PD-0325901 in patients with NF1-associated 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.