Neurofibromatosis Type 1
Neurofibromatosis type 1 (NF1) is a rare genetic disorder that affects both children and adults. The disorder is characterized by mutations in the NF1 gene, which affects the MAPK pathway. NF1 is the most common form of neurofibromatosis, with an estimated global birth incidence of approximately 1 in 3,000 individuals, and approximately 100,000 patients living with NF1 in the United States. The clinical course of NF1 is heterogeneous and manifests in a variety of symptoms across numerous organ systems, including abnormal pigmentation, skeletal deformities, tumor growth and neurological complications, such as cognitive impairment. Patients with NF1 have an eight to 15-year shortened lifespan compared to the general population.
Throughout their lifetime, about 30-50% of NF1 patients progress to develop plexiform neurofibromas (PN), which are peripheral nerve sheath tumors that cause severe disfigurement, pain and functional impairment. In rare cases, NF1-PN may be fatal. NF1-PN are most often diagnosed in the first two decades of life. These tumors are characterized by aggressive growth, which is typically more rapid during childhood.
Most patients with NF1-PN are treated with surgical removal of the tumors, however, because NF1-PN arise from nerve cells and grow in an infiltrative pattern, it is challenging to successfully resect tumors without severe comorbidities, such as permanent nerve damage and disfigurement. There are no therapies currently approved for the treatment of NF1-PN.
Our Investigational Therapy
Mirdametinib is an oral small molecule designed to inhibit MEK1 and MEK2 that has been tested in Phase 1 and Phase 2 clinical trials. SpringWorks is enrolling patients in the ReNeu trial, a Phase 2b, open-label clinical trial for children and adults with NF1-PN.
The U.S. Food and Drug Administration (FDA) and the European Commission granted Orphan Drug designation for mirdametinib for the treatment of NF1, and 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.
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.