Daiichi Sankyo Makes Available New Dosing Regimen for Turalio

A new dosing regimen is now available for Daiichi Sankyo’s Turalio (pexidartinib) to treat adult patients with symptomatic tenosynovial giant cell tumor (TGCT). A new 125 mg capsule now available and the 200 mg capsule has been discontinued. The new recommended dose, which was approved by the FDA in October 2022, is 250 mg orally twice daily (taken as two 125 mg capsules) with a low-fat meal. The previous dose was 400 mg orally twice daily on an empty stomach.

Tenosynovial giant cell tumor is a rare, typically non-malignant tumor that affects small and large joints. The disease can cause debilitating symptoms, can be locally aggressive and can significantly impact everyday activities in a relatively young patient population.

Dan Switzer

“The new dose reflects study data that evaluated the impact of food on Turalio exposure should patients not follow the previous recommended dietary requirements when taking the medication,” Dan Switzer, head of U.S. Oncology Business, Daiichi Sankyo, said in a press release.

As part of post-marketing requirements with FDA, Daiichi Sankyo conducted pharmacokinetic studies to evaluate the effects of food when taking Turalio. A high-fat meal (about 55 to 65 grams of total fat) was found to increase the concentration of drug in the body and may increase the risk of adverse reactions, including hepatotoxicity. These studies demonstrated that lowering the dose and taking it with a low-fat meal helps to minimize the potential for drug overexposure in the event a patient did not carefully follow the dietary recommendations when taking the 200 mg capsule.

Turalio is approved with a boxed warning for hepatotoxicity due to the risk of serious and potentially fatal liver injury and is only available through a Risk Evaluation and Mitigation Strategy (REMS) program. Across 768 patients who received Turalio in clinical trials, there were two irreversible cases of cholestatic liver injury, which is characterized by a build up of bile acids in serum and hepatocytes. One patient died with advanced cancer and ongoing liver toxicity and one patient required a liver transplant.

In addition, long-term efficacy data from the open-label extension part of the ENLIVEN phase 3 trial has been added to the label of Turalio. Patients who completed treatment in the double-blind, randomized part of the ENLIVEN trial were eligible to advance to an open-label extension. At the completion of the open-label extension, the objective response rate (ORR) was 61% in 61 patients originally randomized to the treatment arm.

The FDA approved Turalio in August 2019.