5 November 2018 - - The US Food and Drug Administration has granted Orphan Drug designation for PD-0325901, an investigational, oral, small molecule selective inhibitor of MEK1 and MEK2, for the treatment neurofibromatosis type 1, US-based biopharmaceutical company SpringWorks Therapeutics said.

Neurofibromatosis type 1, or NF1, is a rare genetic disorder that is caused by mutations in the NF1 gene, and that affects both children and adults.

NF1 mutations can result in a loss of activity in the protein neurofibromin, which can lead to MAPK pathway overactivation, uncontrolled cellular growth, and tumor formation. NF1 is a heterogeneous condition that frequently causes plexiform neurofibromas, which are painful, disfiguring tumors of the peripheral nervous system.

It is estimated that there are approximately 100,000 patients in the United States living with NF1.

The FDA, through its Office of Orphan Products Development, grants orphan drug designation to drugs and biologic products that are intended for treatment of rare diseases or disorders that affect fewer than 200,000 people in the United States.

Orphan drug status is intended to facilitate drug development for rare diseases and may provide certain benefits and incentives to drug developers, including seven years of market exclusivity if the drug is approved, FDA assistance in clinical trial design, and tax credits for qualified clinical trial costs.

SpringWorks expects to initiate a Phase 2b single-arm, open-label study of PD-0325901 in patients with neurofibromatosis type 1-associated plexiform neurofibromas (NF1-associated PN) in the first half of 2019.

Neurofibromatosis type 1, or 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% of NF1 patients progress to a more severe form of the disease that results in the development of plexiform neurofibromas, which are progressive peripheral nerve sheath tumors that cause severe pain, morbidity, and can significantly shorten lifespan.4-6 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.

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 has been observed because of the aggressive nature of these tumors.

There are no therapies currently approved for the treatment of NF1-associated PN.

PD-0325901 is an investigational, oral, small molecule, selective inhibitor of MEK1 and MEK2, proteins that play key roles in the MAPK pathway.

The MAPK pathway is critical for cell survival and proliferation, and overactivation of this pathway has been shown to help enable tumor growth. By blocking activity of the MAPK pathway, PD-0325901 may help arrest uncontrolled cellular growth associated with many types of tumors.

PD-0325901 has been tested in several Phase 1 and Phase 2 clinical trials, and approximately 260 subjects have been exposed to treatment. SpringWorks is evaluating PD-0325901 as a monotherapy for the treatment of patients with neurofibromatosis type 1-associated plexiform neurofibromas (NF1-associated PN).

In addition, given the critical role that the MAPK pathway plays in the growth and proliferation of a large number of tumor types, SpringWorks is also pursuing PD-0325901 in combination with other rational anti-cancer agents across a range of solid tumors.

SpringWorks Therapeutics is a clinical-stage biopharmaceutical company, developing medicines for patients with severe rare diseases and cancer.

Since its launch in 2017, the company has worked to identify, re-prioritize, and advance promising science, beginning with licensed clinical therapies from Pfizer Inc.