As such, pexidartinib is only available through a restricted distribution program known as TURALIO REMS. The program will allow only certified prescribers, certified pharmacies, and enrolled patients to prescribe, dispense, and receive pexidartinib, respectively.
The risk of liver injury, including vanishing bile duct syndrome, has been added to the prescribing information for pexidartinib.2,3 When prescribing pexidartinib, it is recommended that clinicians monitor liver tests, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, direct bilirubin, alkaline phosphatase, and gamma-glutamyl transferase levels before starting treatment; these levels should be monitored weekly for the first 8 weeks, every 2 weeks for the following month, and every 3 months thereafter.2
Doses of pexidartinib should be withheld, reduced, or permanently discontinued, based on the severity of hepatotoxicity. However, this monitoring and full discontinuation of the agent may not eliminate the risk of serious and potentially fatal liver injury. If liver tests do not return to normal, patients should be referred to a hepatologist.
When did the FDA approve pexidartinib in TGCT?
Pexidartinib became the first systemic therapy available for patients with TGCT when the FDA approved the agent in August 2019 for the treatment of adult patients with symptomatic TGCT associated with severe morbidity or functional limitations and not amenable to improvement with surgery.4 The approval was supported by data from the phase 3 ENLIVEN trial (NCT02371369).
Findings from ENLIVEN supporting the approval showed that patients treated with pexidartinib achieved an overall response rate (ORR) of 38% (95% CI, 27%-50%) at week 25, including a complete response rate of 15% and a partial response rate of 23%. Conversely, no patients receiving placebo experienced a response by week 25 (P <.0001).
Notably, 22 of 23 patients who were treated with pexidartinib who experienced a response and had a minimum follow-up of 6 months remained in response for at least 6 months. All 13 responders who were followed for at least 12 months maintained their response for at least 12 months.
Pexidartinib was also associated with a statistically significant improvement vs placebo in terms of range of motion of the affected joint at week 25 vs baseline.
The most common adverse effects (AEs) reported in the pexidartinib arm comprised increased lactate dehydrogenase levels, increased AST levels, hair color changes, increased ALT levels, and increased cholesterol. Other AEs included neutropenia, increased alkaline phosphatase levels, decreased lymphocyte counts, eye edema, decreased hemoglobin levels, rash, dysgeusia, and decreased phosphate levels.
How was the ENLIVEN trial designed?
ENLIVEN was a double-blind, randomized, placebo-controlled study that enrolled patients at least 18 years of age with histologically confirmed pigmented villonodular synovitis or giant cell tumor of the tendon sheath, for whom surgical resection would be associated with potentially worsening functional limitation or severe morbidity.5 Patients needed to have measurable disease of at least 2 cm per RECIST 1.1 criteria, symptomatic disease, and adequate hematologic, hepatic, and renal function.
The study excluded patients who received prior treatment with pexidartinib or any biologic treatment targeting CSF-1 or the CSF-1R, although prior TKI use was permitted.
Patients were randomly assigned to receive pexidartinib at 1000 mg per day for 2 weeks followed by 800 mg per day for 22 weeks, or matching placebo.
ORR served as the trial’s primary end point. Secondary end points included mean change in range of motion score, ORR based on tumor volume score, patient-reported outcomes, duration of response, and safety.
References
- REMS safety update on Turalio. News release. ASCO. November 3, 2025. Accessed November 4, 2025. https://www.asco.org/news-initiatives/policy-news-analysis/rems-safety-update-turalio
- Turalio REMS: Letter for healthcare providers. Daiichi Sankyo. Accessed November 4, 2025. https://www.turaliorems.com/pdfs/LetterForHealthcareProvider
- Turalio. Prescribing information. Daiichi Sankyo. Updated January 2025. Accessed November 4, 2025. https://daiichisankyo.us/prescribing-information-portlet/getPIContent?productName=Turalio&inline=true
- FDA approves pexidartinib for tenosynovial giant cell tumor. FDA. August 2, 2019. Accessed November 4, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pexidartinib-tenosynovial-giant-cell-tumor
- Phase 3 study of pexidartinib for pigmented villonodular synovitis (PVNS) or giant cell tumor of the tendon sheath (GCT-TS) (ENLIVEN). ClinicalTrials.gov. Updated May 11, 2022. Accessed November 4, 2025. https://clinicaltrials.gov/study/NCT02371369
