The FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 12-3 that the benefits of pexidartinib outweigh the risks for the treatment of adults with tenosynovial giant cell tumor (TGCT) not amenable to surgical resection.

If approved, pexidartinib (Daiichi Sankyo) — a novel, oral small molecule inhibitor of colony stimulating factor-1 receptor, the primary growth driver of abnormal cells in the synovium that cause tenosynovial giant cell tumor (TGCT) — would be the first FDA-approved therapy for this rare debilitating disease.

“Today’s vote in favor of pexidartinib marks a significant step toward delivering the first approved systemic therapy for select TGCT patients whose disease is not amenable to improvement with surgery,” said Antoine Yver, MD, MSc, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo. “Some people living with TGCT experience debilitating symptoms and need innovative treatment options. We believe that pexidartinib has the potential to help address this need by offering carefully selected TGCT patients an important treatment advancement, and we look forward to working with the FDA as it completes its review of our application.”

The New Drug Application (NDA) for pexidartinib is currently under Priority Review in the U.S., and the FDA is expected to decide whether to approve the application by the PDUFA date of August 3, 2019. The FDA will consider today’s vote as it reviews the NDA, although it is not obligated to follow the Committee’s recommendation. The NDA submission is based on the results of the pivotal phase 3 ENLIVEN study of oral pexidartinib, the first placebo-controlled study of a systemic investigational therapy in patients with TGCT.

The ENLIVEN study met its primary endpoint of tumor response rate by RECIST, which was 39% in pexidartinib-treated patients and zero percent for placebo-treated patients at week 25 (p <0.0001). In the ENLIVEN study, hepatic toxicities were more frequent with pexidartinib versus placebo (aspartate aminotransferase [AST] or alanine aminotransferase [ALT] ≥3X the upper limit of normal [ULN]: 33 percent, total bilirubin ≥2X ULN: 5 percent, N=61). In the randomized Part 1 of the study, eight (13%) patients discontinued pexidartinib due to adverse events (AEs); one discontinuation was due to hypertension and seven were due to liver-related AEs occurring within the first two months of treatment. Of the liver-related AEs, three were serious nonfatal AEs with increased bilirubin, one lasting ~7 months. In non-TGCT development studies using pexidartinib, two severe liver toxicity cases (one required liver transplant, one was associated with death) were observed.

The company’s full press release can be found here.