Vimseltinib, marketed as Romvimza, is an oral therapeutic agent. This small molecule inhibitor is a tyrosine kinase inhibitor. It offers a targeted approach for diseases driven by specific cellular signaling pathways, focusing on particular molecular targets.
Conditions Treated
Vimseltinib is approved for the treatment of symptomatic tenosynovial giant cell tumor (TGCT) in adults. TGCT is a rare, non-cancerous tumor affecting the tissue lining joints, tendons, and bursae. These tumors can be locally aggressive, causing pain, swelling, stiffness, and restricted joint movement. The disease leads to functional limitations and disability, with many patients experiencing tumor recurrence even after surgical removal.
New treatment options are needed for TGCT, particularly when surgery is not feasible or would worsen functional limitation. Current treatments, primarily surgery, often result in recurrence. Vimseltinib offers a less invasive alternative, addressing the underlying genetic drivers of TGCT.
How It Works
Vimseltinib functions as a selective inhibitor of the colony-stimulating factor 1 receptor (CSF1R). This receptor, a type III receptor tyrosine kinase, plays a role in the growth, survival, and differentiation of myeloid lineage cells, including macrophages. In TGCT, a genetic alteration leads to the overproduction of colony-stimulating factor 1 (CSF1), which then activates CSF1R. This activation recruits and promotes the proliferation of CSF1R-dependent inflammatory macrophages, which contribute to tumor growth.
Vimseltinib is an “oral switch-control” tyrosine kinase inhibitor that binds to a unique regulatory region, or “switch pocket,” of the CSF1R. By occupying this pocket, vimseltinib stabilizes the CSF1R in an inactive conformation, preventing its activation by CSF1 and interleukin-34 (IL-34) ligands. This inhibition blocks CSF1R-mediated signaling, which in turn reduces the recruitment and activity of tumor-associated macrophages (TAMs). By depleting these macrophages, vimseltinib inhibits tumor cell proliferation and can reduce tumor size. Vimseltinib is highly selective for CSF1R, which helps minimize off-target effects.
Patient Considerations
Patients treated with vimseltinib may experience therapeutic benefits, including tumor volume reduction. Patients also reported improvements in their active range of motion, physical function, joint stiffness, and a reduction in pain. These improvements can lead to a better overall quality of life for individuals living with TGCT.
While generally well-tolerated, vimseltinib can cause some side effects, most are mild to moderate. Common side effects include periorbital edema (swelling around the eyes), fatigue, face edema, pruritus (itching), and headache. Some patients may also experience increased levels of liver enzymes and cholesterol, as well as decreased white blood cell counts. Unlike some other CSF1R inhibitors, vimseltinib has not been associated with severe liver toxicity. Patients should discuss with their healthcare provider if vimseltinib is a suitable option.
Development Status
Vimseltinib received approval from the U.S. Food and Drug Administration (FDA) in February 2025 for the treatment of symptomatic tenosynovial giant cell tumor (TGCT) in adults when surgical removal is not feasible or could worsen functional limitation. This approval was based on results from the international Phase 3 MOTION trial, which demonstrated a statistically significant objective response rate of 40% in patients receiving vimseltinib compared to none in the placebo group at week 25.
The European Medicines Agency (EMA) accepted a Marketing Authorization Application for vimseltinib in mid-July 2024, initiating its centralized review process. Vimseltinib offers a new targeted therapy option for patients with TGCT who have limited treatment alternatives.