The FDA has approved vimseltinib for the treatment of adult patients with symptomatic tenosynovial giant cell tumors (TGCT) who are not candidates for surgical resection. This marks the second colony-stimulating factor 1 receptor (CSF1R) blocker available for this indication, following the approval of pexidartinib in 2019. Another CSF1R blocker is currently in development.
TGCT is a nonmalignant tumor that arises in the synovial membrane of joints, bursae, and tendons. The condition is rare, with an annual incidence of approximately one to two cases per million people in the United States. Surgery is typically the first-line treatment, but in cases where resection could lead to significant joint dysfunction or other complications, medical therapy is necessary.
The underlying cause of TGCT is linked to the dysregulation of the CSF1 gene, which results in the overproduction of CSF1. This leads to an accumulation of CSF1-positive macrophages in the synovium, contributing to tumor formation and associated symptoms. Both vimseltinib and pexidartinib work by blocking CSF1 signaling, thereby targeting the root cause of the disease.
The approval of vimseltinib was based on results from the MOTION trial, which included 123 patients for whom surgery was not a viable option due to the risk of impaired joint function or severe morbidity. Patients were randomly assigned in a 2:1 ratio to receive either vimseltinib at a dose of 30 mg twice weekly or a placebo for a 24-week period.
At the 25-week mark, the objective response rate was 40% in the vimseltinib-treated group, whereas no responses were observed in the placebo group. The median duration of response was not reached in the vimseltinib arm. Additional follow-up data revealed that 85% of responders maintained their response for at least six months, and 58% maintained their response for nine months or longer.
Patients treated with vimseltinib also experienced significant improvements in active range of motion, physical functioning, and pain levels. These benefits suggest that the drug not only reduces tumor burden but also enhances quality of life for those affected by the condition.
The safety profile of vimseltinib was generally favorable, with most treatment-emergent adverse events classified as grade 1 or 2. The most frequently reported side effects, occurring in at least 20% of patients, included elevated aspartate aminotransferase levels, periorbital edema, fatigue, rash, and increased cholesterol levels. Importantly, there was no indication of liver toxicity or injury associated with vimseltinib, a key distinction from pexidartinib, which carries a warning for potentially fatal liver injury.
The approval of vimseltinib provides an important new option for patients with TGCT who are not suitable candidates for surgery. Its demonstrated efficacy, along with its favorable safety profile, makes it a valuable addition to the treatment landscape for this rare and debilitating condition.
