Based on findings from the phase III ENLIVEN study, a new drug application (NDA) for the investigational, small molecule, CSF1R receptor inhibitor pexidartinib has been granted a priority review by the FDA for the treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT).1
Findings from the trial showed a 39.3% overall response rate with pexidartinib versus 0% with placebo after 24 weeks of treatment based on central review of magnetic resonance imaging scans.2 Under the Prescription Drug User Fee Act, the FDA is scheduled to make a decision on the approval by August 3, 2019.
“We are pleased to announce that the FDA has accepted our application for pexidartinib with priority review designation, potentially bringing a treatment option to patients for whom there is no approved therapy,” said Dale Shuster, PhD, executive director, Global Oncology R&D, Daiichi Sankyo, the manufacturer of pexidartinib.
“Current treatment options for TGCT are largely limited to surgery, but for some patients the disease is debilitating and not amenable to improvement with surgery. We are committed to working with the FDA to potentially bring pexidartinib to carefully selected patients as soon as possible,” added Shuster.
TGCT, which is also referred to as pigmented villonodular synovitis or giant cell tumor of the tendon sheath, is a nonmalignant tumor of the joint or tendon sheath. TGCT is said to be locally aggressive and debilitating in some patients, and is associated with severe morbidity or function limitations. Currently, there are no FDA-approved systemic therapies for TGCT, and surgery is the primary treatment.
In the international, multicenter, double-blind, phase III ENLIVEN study, investigators evaluated pexidartinib in patients with symptomatic advanced TGCT in whom surgical removal of the tumor would lead to potentially worsening functional limitation or severe morbidity. In the first part of the study, which was the double-blind phase, 120 patients were randomized 1:1 to receive either pexidartinib or placebo at 1000 mg daily for 2 weeks followed by 800 mg daily for 22 weeks.
The primary endpoint of the study was the percentage of patients achieving a complete or partial response, assessed with centrally read MRI scans using RECIST 1.1 criteria, after 24 weeks of treatment. Secondary endpoints included range of motion, response by tumor volume score, Patient-Reported Outcomes Measurement Information System physical function, stiffness, and measures of pain reduction.