The world's first targeted drug for TGCT failed to gain approval in China

Reposted from: Qin Jiao New Drug Society

Today’s NMPA drug delivery information shows that Daiichi Sankyo’sPexidartinib hydrochloride capsules (Pexidartinib, PLX3397), unfortunately received a notice。

Image source: NMPA official website

Pexidartinib hydrochloride was initially discovered by Plexxikon and later incorporated into Daiichi Sankyo's development pipeline. It is an orally administered small-molecule tyrosine kinase inhibitor, with its core target being CSF1R (colony-stimulating factor 1 receptor), while also inhibiting KIT and FLT3-ITD. Its development rationale primarily addresses the abnormal activation of the CSF1/CSF1R pathway in TGCT (tenosynovial giant cell tumor), which drives synovial macrophage aggregation and lesion proliferation.

As a milestone drug in the rare disease field of tenosynovial giant cell tumor (TGCT)First-in-class targeted therapyand is currently theworld's firsttargeted treatment for tenosynovial giant cell tumor (TGCT). This drugdemonstrated an objective response rate of approximately 38% in the ENLIVEN studyand gained FDA approval for marketing in 2019 under the trade name Turalio, indicated for adult patients with symptomatic TGCT who have severe morbidity or functional limitations and are not amenable to improvement through surgery.

In terms of safety,The main clinical limitation of pexidartinib hydrochloride is hepatotoxicity.. Both the FDA label and company updates emphasize that the drug can cause severe and potentially fatal liver injury, prompting the United States to implement aRisk Evaluation and Mitigation Strategy (REMS)management plan.

In 2020, the EMA issued arefusal to grant marketing authorizationopinion on Turalio. The core reason given by the EMA was:Although tumor shrinkage was observed in the studies, the improvement in symptoms such as pain and joint function was limited in magnitude and not sufficiently sustained. Additionally, there were concerns about unpredictable and potentially life-threatening hepatotoxicity, leading to the conclusion that the benefits did not outweigh the risks.。

Image Source: EMA official website

In 2022, the FDA approved a new dosing regimen and incorporated some long-term follow-up data into the label. The current recommended dose shown on the US label is 250mg twice daily with a low-fat meal; this regimen replaces the earlier high-dose fasting administration to reduce the risk of increased exposure and hepatotoxicity due to food intake.

Regarding East Asian bridging studies, results from NCT04488822 published in 2025 showed that among 40 East Asian patients with TGCT, at week 25The ORR assessed by RECIST was 22.5%, and the ORR assessed by TVS was 47.5%with significant improvement in joint mobility; the author considered its safety to be generally consistent with previous studies

Image source: Literature

In January 2025, the drug's marketing application was submitted in China and granted priority review, but unfortunately, it was not approvedI wonder if the CDE referenced the EMA’s opinion and similarly assessed that the drug’s risks outweigh its benefits?

References: Turalio package insert, official press release from Daiichi Sankyo, literature - A Phase 3 Study of the Efficacy and Safety of Pexidartinib in East Asian Patients with Tenosynovial Giant Cell Tumor

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