Vimseltinib Receives FDA Approval for Tenosynovial Giant Cell Tumor

On 14 February 2025, the US Food and Drug Administration (FDA) approved treatment for adults with symptomatic tenosynovial giant cell tumor (TGCT) using  vimseltinib (Romvimza, Deciphera Pharmaceuticals, LLC), a kinase inhibitor. The drug was developed for situations in which surgical tumor removal could worsen functional limitations or cause serious additional morbidity.

Vimseltinib: The Second FDA Approval for TGCT Treatment

Vimseltinib, a colony-stimulating factor 1 receptor (CSF1R) inhibitor, follows pexidartinib (Turalio, Daiichi), approved in 2019, as the second drug approved for this indication in the US. A third CSF1R inhibitor, developed by Merck, is also in clinical development.

What Is TGCT and Why Does It Matter?

Tenosynovial giant cell tumor (TGCT) is a nonmalignant (benign) tumor arising in the synovial membrane surrounding joints, bursae and tendons. Its annual incidence in the US is estimated at 1 to 2 cases per million people. Surgery is generally the first-choice treatment for TGCT.

The disease results from dysregulation of the CSF1 gene, leading to excessive CSF1 production. This causes CSF1-positive macrophages to accumulate in the synovium. Both vimseltinib and pexidartinib aim to interrupt this process by blocking the CSF1 signaling pathway.

FDA Approval Based on the MOTION Trial

Vimseltinib's efficacy was evaluated in MOTION (NCT05059262), a double-blind, multicenter, randomized (2:1), placebo-controlled clinical trial.

The trial included patients with TGCT for whom surgical resection could worsen functional limitations or cause serious morbidity.

Participants had to have measurable tumors according to RECIST v1.1, including at least one lesion measuring 2 cm or more.

Patients were randomized to receive vimseltinib 30 mg twice weekly or placebo for 24 weeks.

The trial had two phases:

1. A double-blind period and
2. An open-label period

During the open-label period, patients already receiving vimseltinib could continue treatment, while those receiving placebo could switch to vimseltinib.

Randomization was stratified by tumor location (lower limb versus other sites) and geographical location (the US versus other countries).

A total of 123 patients were enrolled: 83 were assigned to vimseltinib and 40 to placebo.

Trial Results

The primary efficacy measure was the overall response rate at week 25, assessed by blinded independent radiological review. The findings were as follows:

• The overall response rate in the vimseltinib arm was 40% (95% CI: 29%, 51%)
• In the placebo arm, it was 0% (95% CI: 0%, 9%) (p<0.0001)

Median response duration had not yet been reached in the vimseltinib arm. During an additional 6 months of follow-up, responses lasted at least 6 months in 28 responders (85%) and more than 9 months in 19 patients (58%).

At week 25, patients receiving vimseltinib also had statistically significant improvements over placebo in active range of motion, patient-reported physical function and pain scores.

Adverse Events and Administration

The most common adverse events, occurring in 20% or more of patients, were:

• Laboratory abnormalities: Increased aspartate aminotransferase (AST), increased alanine aminotransferase (ALT), increased cholesterol, Decreased neutrophils and decreased leukocytes
• Clinical symptoms: Periorbital edema, fatigue, rash, peripheral edema, facial edema and itching

The recommended vimseltinib dose, with 72-hour intervals between administrations, is 30 mg as oral tablets twice weekly.

Conclusion and Clinical Significance

Vimseltinib was approved as an important treatment option for patients with TGCT who are not suitable for surgery or in whom surgery could cause serious complications. Clinical trial findings showed that the drug increased objective response rates and substantially improved quality of life.

Further follow-up studies remain important to obtain more information about the drug's long-term efficacy and safety. Among CSF1R inhibitors, vimseltinib offers a new treatment option as an alternative to surgery.