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WASHINGTON -- The first therapy for the rare disease tenosynovial giant cell tumors (TGCT) won FDA approval on Friday.

Pexidartinib (Turalio) was OK'd for adults with symptomatic TGCT associated with severe morbidity or functional limitation and not responsive to surgery. The approval came with the requirement of a boxed warning about a risk of serious and potentially fatal liver disease, as well as a Risk Evaluation and Mitigation Strategy to monitor for liver injury and learn more about the mechanisms of liver injury.

"(TGCT) can significantly affect a patient's quality of life and cause severe disability," Richard Pazdur, MD, of the FDA Office of Hematology and Oncology Products, said . "Surgery is the primary treatment option, but some patients are not eligible for surgery, and tumors can recur, even after the procedure. Today's approval is the first FDA-approved therapy to treat this rare disease."

TGCT arises in the synovium covering the surface of joint spaces and in tendon sheaths. Though rarely malignant, the tumor causes thickening and overgrowth of the synovium and tendon sheaths, damaging surrounding tissues. Each year, about 15,000 people develop localized TGCT, which usually is benign and can be cured by surgery. However, an additional 1,500 cases are diffuse at diagnosis and cannot always be treated with surgery.

Pexidartinib inhibits colony stimulating factor-1 receptor, the primary driver of abnormal cell growth that leads to TGCT. Primary support for approval came from an international multicenter clinical trial involving 120 patients with TGCT, randomized 1:1 to pexidartinib or placebo. The primary endpoint was overall response rate after 25 weeks of treatment.

Pexidartinib treatment led to objective responses in 38% of patients, including a complete response rate of 15%. All but one of 23 responders followed for at least 6 months maintained the response at that point or beyond, and all 12 patients followed for at least 12 months had ongoing responses at 12 months or beyond.

In May, the FDA Oncologic Drugs Advisory Committee voted 12-3 to recommend approval of pexidartinib, despite some concerns about liver toxicity. During the randomized trial, adverse events occurred almost four times as often in the pexidartinib group, and serious adverse events occurred more than six times as often (13% vs 2%). Additionally, 38% of patients in the pexidartinib group required dose reductions or interruptions as compared with 10% of the placebo group, and 13% of patients randomized to pexidartinib stopped treatment versus 0% in the placebo group.

The drug is made by Daiichi Sankyo.

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