FDA Approves Vimseltinib for the Treatment of Adults With Symptomatic TGCT

Author(s):

Gillian McGovern, Associate Editor

Key Takeaways

Vimseltinib selectively inhibits CSF1R, targeting TGCT, a benign tumor causing joint damage and functional limitations.
The MOTION study showed a 40% objective response rate for vimseltinib, significantly outperforming placebo.
Most adverse events were mild, with increased creatine phosphokinase as the only severe event in over 5% of patients.
The FDA approval offers a new treatment option for TGCT patients, especially when surgery poses significant risks.

The indication is for symptomatic tenosynovial giant cell tumor (TGCT) for which surgical resection will potentially cause worsening functional limitation or severe morbidity.

The FDA approved vimseltinib (Deciphera Pharmaceuticals) for the treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT) for which surgical resection will potentially cause worsening functional limitation or severe morbidity.¹ The approval is supported by findings from the MOTION study (NCT05059262).²

Image credit: Grandbrothers | stock.adobe.com

Developed using a proprietary switch-control kinase inhibitor platform, vimseltinib is an investigational oral switch-control tyrosine kinase inhibitor designed to selectively inhibit colony-stimulating factor 1 receptor (CSF1R). It is indicated for TGCT, a rare disease caused by the translocation of the CSF1 gene resulting in overexpression of CSF1 and recruitment of CSF1R-positive inflammatory cells into the lesion. It is a non-malignant tumor that develops inside or near the patients’ joints. Although these tumors are benign, they can grow and cause damage to surrounding tissues and structures, inducing pain, swelling, and limitation of movement of the joint. Surgery is the primary treatment option; however, the tumors often recur—particularly in diffuse-type TGCT—and if left untreated or if it continually recurs, damage and degeneration may develop in the affected joint and surrounding tissues, potentially causing significant disability.³

The approval comes after the MOTION study, a 2-part, randomized, double-blind, placebo-controlled phase 3 clinical trial, which assessed the efficacy and safety of vimseltinib in 123 patients with TGCT not responsive to surgery and without prior anti-CSF1/CSF1R therapy.² Part 1 consists of assigning eligible study participants to receive either vimseltinib (n = 83) or a matching placebo (n = 40; 30 mg twice per week) for 24 weeks. In part 2, patients who received placebo in part 1 were given the option to receive vimseltinib and received the drug for a long-term period in an open-label setting.^2-4

The primary end point was objective response rate (ORR) in the intent to treat population compared with placebo, and secondary end points include ORR per tumor volume score, active range of motion, physical function, stiffness, quality of life, and pain, all of which were assessed at 25 weeks (day 1 of cycle 7).²

The findings demonstrated that ORR was approximately 40% (n = 33) in the vimseltinib group compared with 0% in the placebo group (95% CI 29–51; p < .0001). Most of the treatment-emergent adverse events (AEs) observed were grades 1 or 2 in severity. The only grade 3 or 4 treatment-emergent AE that occurred in more than 5% of patients receiving vimseltinib was increased creatine phosphokinase (10%; n = 8). There was 1 incidence of serious subcutaneous abscess, and no evidence of cholestatic hepatotoxicity or drug-induced liver injury was observed. Other common AEs, including laboratory abnormalities, were increased aspartate aminotransferase, cholesterol, and alanine aminotransferase; decreased neutrophils and leukocytes; pruritus; periorbital edema; fatigue; rash; peripheral edema; and face edema.⁴

About the Trial

Trial Name: Study of Vimseltinib for Tenosynovial Giant Cell Tumor (MOTION)

ClinicalTrials.gov ID: NCT05059262

Sponsor: Deciphera Pharmaceuticals, LLC

Completion Date (Estimated): July 2026

“Building upon positive results from the MOTION pivotal phase 3 study and following our recent announcement that [European Medicines Agency] review of the vimseltinib [marketing authorization application] has begun, we are excited to initiate the regulatory review process in the US, and we look forward to working with the FDA to deliver a new treatment option to patients with TGCT,” said Steve Hoerter, president and CEO of Deciphera Pharmaceuticals, in a news release.²

REFERENCES

1. US Food and Drug Administration. FDA approves vimseltinib for symptomatic tenosynovial giant cell tumor. News release. February 14, 2025. Accessed February 15, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-vimseltinib-symptomatic-tenosynovial-giant-cell-tumor

2. Study of Vimseltinib for Tenosynovial Giant Cell Tumor (MOTION). ClinicalTrials.gov identifier: NCT05059262. Updated August 9, 2024. Accessed February 7, 2025. https://clinicaltrials.gov/study/NCT05059262

3. Ono Pharma. U.S. Food and Drug Administration Accepts for Priority Review Deciphera’s New Drug Application for Vimseltinib for the Treatment of Patients with Tenosynovial Giant Cell Tumor (TGCT). News release. August 16, 2024. Accessed February 7, 2025. https://www.ono-pharma.com/en/news/20240816.html

4. Gelderblom H, Bhadri V, Stacchiotti S, et al. Vimseltinib versus placebo for tenosynovial giant cell tumour (MOTION): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet. 2024;403(10445):2709–2719. doi:10.1016/S0140-6736(24)00885-7Top of FormBottom of Form