The U.S. Food and Drug Administration has granted Breakthrough Therapy and Orphan Drug designation to pexidartinib (formerly PLX3397) for the treatment of tenosynovial giant cell tumor (TGCT) where surgical removal of the tumor would be associated with potentially worsening functional limitation or severe morbidity. Pexidartinib is an investigational oral small molecule that potently and selectively inhibits colony-stimulating factor-1 receptor (CSF-1R).
The Breakthrough Therapy designation, enacted as part of the FDA's 2012 Safety and Innovation Act, was created to expedite the development and review time of a potential new drug for serious or life-threatening disease where early clinical evidence suggests the drug may demonstrate substantial improvement compared with existing therapies.
The Orphan Drug designation—to encourage development of drugs in the diagnosis, prevention, or treatment of a medical condition affecting fewer than 200,000 people in the U.S.—grants a product market exclusivity for a seven-year period if the sponsor complies with certain FDA specifications, as well as tax credits and prescription drug user fee waivers. The designation does not, though, shorten the duration of the regulatory review and approval process.
Currently, there is no FDA-approved systemic therapy for the treatment of TGCT, notes a news release from Daiichi Sankyo, Inc., and Plexxikon Inc., who are developing the drug.
The designations for pexidartinib were granted based on results from an extension cohort of a single-arm, multicenter Phase I study that assessed the safety and efficacy of pexidartinib, which provided the proof-of-concept that selective CSF-1R inhibition with pexidartinib may safely and effectively reduce tumor burden in patients with TGCT.
The Phase III study of pexidartinib, called ENLIVEN, is currently enrolling patients with symptomatic TGCT for whom surgical removal of the tumor would be associated with potentially worsening functional limitation or severe morbidity.
The most common treatment-related adverse events seen in the ongoing Phase I study of pexidartinib included fatigue, hair color changes, nausea, dysgeusia, and periorbital edema. Treatment-related severe adverse events included fatigue, diarrhea, anemia, hyponatremia, elevated liver enzymes, and neutropenia.