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SpringWorks Therapeutics Announces FDA Fast Track Designation for PD-0325901 for the Treatment of a Severe Form of Neurofibromatosis Type 1

June 3, 2019 at 6:30 AM EDT

STAMFORD, Conn.--()--SpringWorks Therapeutics, Inc., a clinical-stage biopharmaceutical company focused on developing life-changing medicines for patients with severe rare diseases and cancer, today announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for PD-0325901, an investigational, oral, small molecule inhibitor of MEK1 and MEK2, for the treatment of patients ≥ 2 years of age with neurofibromatosis type 1-associated inoperable plexiform neurofibromas that are progressing or causing significant morbidity.

Neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PN) is a rare genetic disorder characterized by mutations in the MAPK pathway, leading to the growth of peripheral nerve sheath tumors that cause significant pain, disfigurement and morbidity. NF1-PNs are most often diagnosed in the first two decades of life and are characterized by aggressive tumor growth, which is typically more rapid during childhood.1-3 There are currently no therapies approved for the treatment of NF1-PN.

“The Fast Track designation recognizes that plexiform neurofibromas have a substantial impact on the lives of patients, and that our MEK inhibitor has the potential to address the significant needs faced by this patient community who currently do not have an FDA-approved treatment,” said Saqib Islam, Chief Executive Officer of SpringWorks Therapeutics. “We look forward to continuing to work closely with the FDA on our upcoming Phase 2b study, which will enroll pediatric and adult NF1 patients with plexiform neurofibromas.”

The FDA's Fast Track program is designed to expedite the development and review of drugs with the potential to treat serious or life-threatening conditions, and with nonclinical or clinical data that demonstrate the potential to address unmet medical needs. Fast Track designation enables a company to have frequent communication with the FDA throughout the drug development and review process.4

In November 2018, the FDA granted Orphan Drug designation for PD-0325901 for the treatment of neurofibromatosis type 1. SpringWorks expects to initiate a Phase 2b single-arm, open-label study of PD-0325901 in pediatric and adult patients with NF1-PN in the third quarter of 2019.

About Neurofibromatosis Type 1
Neurofibromatosis type 1 (NF1) is a rare genetic disorder that is caused by mutations in the NF1 gene, and that affects both children and adults. Throughout their lifetime, about 30 to 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 cause severe pain, disfigurement, debilitating loss of range of motion, and can significantly shorten lifespan.1-3The 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.5 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 has been observed because of the aggressive nature of these tumors.6 There are no therapies currently approved for the treatment of NF1-PN.

About PD-0325901

PD-0325901 is an oral small molecule inhibitor of MEK1 and MEK2. MEK proteins occupy a pivotal position in the MAPK pathway, a key signaling network that regulates cell growth and survival, and whose activity is highly relevant in multiple oncology and rare disease indications.

PD-0325901 has been evaluated in several Phase 1 and Phase 2 clinical trials, with over 200 subjects having been exposed to treatment. A Phase 2 trial conducted by the Neurofibromatosis Clinical Trial Consortium evaluated PD-0325901 in 19 adolescent and adult patients with inoperable and symptomatic or growing plexiform neurofibromas. Results demonstrated an objective response in 42 percent of patients, prospectively defined as having greater than or equal to 20 percent reduction in tumor volume as measured by volumetric MRI. In the clinical trial, PD-0325901 given at 2mg/m2 on a 3-week on 1-week off schedule was generally well-tolerated. The most commonly reported treatment-emergent grade 2 or higher AEs were acneiform rash in 53% (10/19), fatigue in 26% (5/19) and nausea in 21% (4/19) of patients.

SpringWorks is evaluating PD-0325901 as a monotherapy for the treatment of patients with NF1-PN and is also pursuing PD-0325901 in combination with other rational anti-cancer agents across a range of solid tumors.

About SpringWorks Therapeutics

At SpringWorks Therapeutics, a clinical-stage biopharmaceutical company, we are driven to develop life-changing medicines for patients with severe rare diseases and cancer. Since our launch in 2017, we have worked to identify and advance promising science, beginning with our licensed clinical therapies from Pfizer Inc. We pioneer efficient pathways for drug development, leveraging shared-value partnerships with patient advocacy groups, innovators in industry and academia, and investors so that together, we can unlock the potential of science and bring new therapies to underserved patients. Nirogacestat, our gamma secretase inhibitor for the treatment of desmoid tumors is currently in a Phase 3 clinical trial, and SpringWorks Therapeutics expects to initiate a Phase 2b study of PD-0325901, our MEK 1/2 inhibitor for neurofibromatosis type 1 patients with plexiform neurofibromas, in the third quarter of 2019. PD-0325901 also holds promise as the backbone for combination therapies to treat metastatic solid tumors. At SpringWorks Therapeutics, we ignite the power of promising science to unleash new possibilities for patients. For more information, please visit


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.

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 U.S. Food & Drug Administration. (2018). Fast Track. Retrieved from

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.

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.


Kim Diamond
Vice President, Communications and Investor Relations
Phone: 646-661-1255

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