Daiichi Sankyo announced the FDA has approved Turalio (pexidartinib) for adults with symptomatic tenosynovial giant cell tumor (TGCT), a rare, non-malignant tumor that can be aggressive locally. Turalio is approved only for patients for whom surgery is not an option. Turalio is approved with a Boxed Warning for hepatotoxicity due to the risk of serious and potentially fatal liver injury. Because of the risk of hepatotoxicity, Turalio will be available only through a restricted program called the TURALIO Risk Evaluation and Mitigation Strategy (REMS) Program. Under this program, only certified healthcare providers may prescribe Turalio.
The FDA approval of Turalio was based on ENLIVEN, a double-blind, randomized, placebo-controlled, global multi-center, pivotal phase 3 study, which evaluated Turalio in patients with symptomatic TGCT for whom surgical removal of the tumor would be associated with potentially worsening functional limitation or severe morbidity. The first part of the study, the double-blind phase, enrolled 120 patients who were randomized (1:1) to receive either Turalio at 1000 mg/day for 2 weeks followed by 800 mg/day for 22 weeks or matching placebo, to evaluate the efficacy and safety of Turalio versus placebo. Study results showed the primary endpoint of tumor response rate by Response Evaluation Criteria v1.1 in Solid Tumors (RECIST) was 38% in Turalio-treated patients and zero percent for placebo-treated patients at Week 25. In addition, overall response rate by tumor volume score (TVS) was 56% in patients randomized to the Turalio and 0% in patients randomized to the placebo arm at Week 25. Furthermore, the analysis of mean change from baseline in range of motion at Week 25 demonstrated a statistically significant improvement in patients treated with Turalio compared to placebo.
Turalio was granted Priority Review, Breakthrough Therapy designation and Orphan Drug status by the U.S. FDA. Pexidartinib has received Orphan Drug designation from the European Medicines Agency (EMA) and is currently under regulatory review for the treatment of TGCT.
About TGCT (PVNS/GCT-TS)
TGCT, also referred to as pigmented villonodular synovitis (PVNS) or giant cell tumor of the tendon sheath (GCT-TS), is a rare, non-malignant tumor that can be locally aggressive. TGCT affects the synovium-lined joints, bursae and tendon sheaths, resulting in reduced mobility in the affected joint or limb. The current standard of care for TGCT is surgical resection. However, in patients with a recurrent, difficult-to-treat, or diffuse form of TGCT, the tumor may wrap around bone, tendons, ligaments and other parts of the joint. In these cases, the tumor may be difficult to remove and/or may not be amenable to improvement with surgery. Multiple surgeries for more severe cases can lead to significant joint damage, debilitating functional impairments and reduced quality of life, and amputation may be considered.
About Turalio (pexidartinib)
Turalio (pexidartinib) is an oral small molecule that inhibits CSF1R (colony stimulating factor-1 receptor), which is a primary growth driver of abnormal cells in the synovium that cause TGCT. Turalio also inhibits KIT and FLT3-ITD.