FDA Approves First Therapy for Adults with Rare TGCT

Officials with the FDA have granted approval to pexidartinib (Turalio, Daiichi Sankyo) capsules for the treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not responsive to improvement with surgery.

Announced Friday, this approval is the first by the FDA for a therapy used to treat TGCT, a rare disease. The agency granted Breakthrough Therapy and Priority Review designations, as well as Orphan Drug designation, to Daiichi Sankyo’s application.

TGCT is rarely malignant but causes the synovium and tendon sheaths to thicken and overgrow, causing damage to surrounding tissue.

“TGCT can cause debilitating symptoms for patients such as pain, stiffness and limitation of movement. The tumor can significantly affect a patient’s quality of life and cause severe disability,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, in a prepared statement. “Surgery is the primary treatment option, but some patients are not eligible for surgery, and tumors can recur, even after the procedure.”

The approval of pexidartinib capsules was based on the results of a multicenter international clinical trial of 120 patients, 59 of whom received placebo. The primary efficacy endpoint was the overall response rate (ORR) analyzed after 25 weeks of treatment. The clinical trial demonstrated a statistically significant improvement in ORR in patients who received pexidartinib, with an ORR of 38%, compared to no responses in patients who received placebo.

The complete response rate was 15% and the partial response rate was 23%. Twenty-two of 23 responders who had been followed for a minimum of 6 months following the initial response maintained their response for 6 or more months, and all 13 responders who had been followed for a minimum of 12 months following the initial response maintained their response for 12 or more months.

Common adverse effects for patients taking pexidartinib were increased lactate dehydrogenase, increased aspartate aminotransferase, loss of hair color, increased alanine aminotransferase and increased cholesterol. Additional adverse effects included neutropenia, increased alkaline, decreased lymphocytes, eye edema, decreased hemoglobin, rash, dysgeusia, and decreased phosphate.

The prescribing information for Daiichi Sankyo’s pexidartinib includes a Boxed Warning to advise health care professionals and patients about the risk of serious and potentially fatal liver injury. The drug is available only through a Risk Evaluation and Mitigation Strategy (REMS) Program.

The FDA also advises health care professionals to tell females of reproductive age and males with a female partner of reproductive potential to use effective contraception during treatment with pexidartinib. Women who are pregnant or breastfeeding should not take pexidartinib because it may cause harm to a developing fetus or newborn baby.

Reference

FDA approves first therapy for rare joint tumor [news release]. Silver Spring, MD; August 2, 2019: FDA website. https://www.fda.gov/news-events/press-announcements/fda-approves-first-therapy-rare-joint-tumor. Accessed August 2, 2019.