Abbisko’s pimicotinib meets primary goal in phase 3 TGCT trial

According to recent topline results, 54% of patients treated with a new therapy experienced tumor shrinkage compared to just 3.2% in the placebo group, successfully meeting the primary endpoint of the trial. Tenosynovial giant cell tumor (TGCT) is a rare disorder primarily caused by the overexpression of the protein colony stimulating factor-1 receptor (CSF-1R). This overexpression drives the proliferation of various cell types, including microglial cells and macrophages, resulting in joint pain, stiffness, and potentially irreversible damage to both joints and bones.

Currently, the primary treatment for TGCT is surgery, though performing the procedure can be difficult for some patients. The only systemic therapy approved by the U.S. Food and Drug Administration is Daiichi Sankyo’s CSF-1R blocker, pexidartinib (Turalio). This medication requires twice-daily dosing and can cause side effects such as hepatotoxicity.

Niu Xiaohui, study investigator and director of the Bone and Soft Tissue Tumour Diagnosis and Research Centre at Beijing Jishuitan Hospital, commented on the findings, saying, "Based on these new data from the MANEUVER study, together with once-daily oral administration that may promote long-term adherence and pimicotinib’s selective inhibition of CSF-1R, this investigational medicine has the potential to establish a new treatment paradigm for patients with TGCT."

The MANEUVER study was a randomized, double-blind, placebo-controlled trial assessing the efficacy of 50 mg pimicotinib taken daily versus a placebo in 94 TGCT patients across Europe, China, and North America who had not previously received CSF-1R blocking treatments. Alongside the primary endpoint, patients in the pimicotinib group also showed significant improvements in secondary endpoints such as stiffness and pain, and the medication was reported to be well-tolerated.

In 2023, Abbisko licensed the commercial rights for pimicotinib in all indications across mainland China, Hong Kong, Macau, and Taiwan to Merck KGaA in a deal worth $70 million upfront. Abbisko also plans to develop pimicotinib for treating solid tumors, chronic graft-versus-host disease, and advanced pancreatic cancer.

Pexidartinib (Turalio) was first approved in the U.S. in 2019, achieving an overall response rate (ORR) of 38% based on phase 3 data. Another promising agent is Deciphera’s vimseltinib, which achieved an ORR of 40% in a phase 3 trial for TGCT treatment conducted last year.

However, CSF-1R blockers have faced challenges in clinical trials for treating other tumor types, potentially due to the heterogeneity of cancer.