General Information

Turalio (pexidartinib) is a kinase inhibitor.

Turalio is specifically indicated for the treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not amenable to improvement with surgery.

Turalio is supplied as a capsule for oral administration. Turalio should be administered on an empty stomach, at least one hour before or two hours after a meal or snack. The recommended dosage of Turalio is 400 mg taken twice daily on an empty stomach until disease progression or unacceptable toxicity. Turalio capsules should be swallowed whole. Do not open, break, or chew the capsules. If a patient vomits or misses a dose of Turalio, instruct the patient to take the next dose at its scheduled time.

Please see drug label for specific dose modifications.

Mechanism of Action

Turalio (pexidartinib) is a small molecule tyrosine kinase inhibitor that targets colony stimulating factor 1 receptor (CSF1R), KIT proto-oncogene receptor tyrosine kinase (KIT), and FMS-like tyrosine kinase 3 (FLT3) harboring an internal tandem duplication (ITD) mutation. Overexpression of the CSF1R ligand promotes cell proliferation and accumulation in the synovium. In vitro, pexidartinib inhibited proliferation of cell lines dependent on CSF1R and ligand-induced autophosphorylation of CSF1R. Pexidartinib also inhibited the proliferation of a CSF1R dependent cell line in vivo.

Side Effects

Adverse effects associated with the use of Turalio may include, but are not limited to, the following:

increased lactate dehydrogenase

increased aspartate aminotransferase

hair color changes

fatigue

increased alanine aminotransferase

decreased neutrophils

increased cholesterol

increased alkaline phosphatase

decreased lymphocytes

eye edema

decreased hemoglobin

rash

dysgeusia

decreased phosphate

The Turalio drug label comes with the following Black Box Warning: HEPATOTOXICITY • Turalio can cause serious and potentially fatal liver injury. Monitor liver tests prior to initiation of Turalio and at specified intervals during treatment. Withhold and dose reduce or permanently discontinue Turalio based on severity of hepatotoxicity. Turalio is available only through a restricted program called the Turalio Risk Evaluation and Mitigation Strategy (REMS) Program.

Clinical Trial Results

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 zero percent 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.