Vimseltinib Earns FDA Priority Review in Tenosynovial Giant Cell Tumor

Supporting data for the NDA came from the phase 3 MOTION study (NCT05059262), in which investigators evaluated the safety and efficacy of vimseltinib in those with TGCT not amenable to surgery.

The FDA has granted priority review to a new drug application (NDA) for the investigational colony stimulating factor 1 receptor (CSF1R) vimseltinib as a treatment for patients with tenosynovial giant cell tumor (TGCT), according to a press release from the developer Ono Pharmaceutical, Co., Ltd.¹

The regulatory agency has set a Prescription Drug User Fee Act date of February 17, 2025, to decide on approving vimseltinib for this indication.

The novel oral switch-control tyrosine kinase inhibitor is designed for selectively inhibiting CSF1R. Developers manufactured the agent using a proprietary switch-control kinase inhibitor platform.

TGCT—a rare, non-malignant tumor that develops inside or near joints—results from a CSF1 gene translocation that causes CSF1 overexpression and CSF1R-positive inflammatory cell recruitment into the lesion. Although TGCTs are benign, they may become larger and subsequently harm surrounding tissues and structures, resulting in pain, swelling, and limited joint movement.

Supporting data for the NDA came from the phase 3 MOTION study (NCT05059262), in which investigators evaluated the safety and efficacy of vimseltinib in those with TGCT not amenable to surgery. According to the press release, the European Medicines Agency (EMA) also accepted a marketing authorization application (MAA) for vimseltinib in July 2024.

“Building upon positive results from the MOTION pivotal phase 3 study and following our recent announcement that EMA review of the vimseltinib MAA has begun, we are excited to initiate the regulatory review process in the [United States] and we look forward to working with the FDA to deliver a new treatment option to patients with TGCT,” Steve Hoerter, president and chief executive officer at Deciphera Pharmaceuticals, the developer of vimseltinib, said in the press release.¹

The double-blind, placebo-controlled MOTION trial consisted of 2 parts. In part 1, patients were assigned to receive vimseltinib or matched placebo for 24 weeks. During part 2 of the study, patients who began treatment with placebo in part 1 were eligible to switch to vimseltinib; all patients were treated with the experimental agent in an open-label setting.

According to findings from the MOTION study presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, treatment with vimseltinib met the primary end point of objective response rate (ORR) at week 25 across the intent-to-treat (ITT) population.² At week 25, the ORR was 40% (95% CI, 29%-51%) with vimseltinib vs 0% (95% CI, 0%-9%) with placebo (P <.0001).

Regarding secondary end points, the ORR per tumor volume score (TVS) was 67% (95% CI, 56%-77%) in the vimseltinib arm compared with 0% (95% CI, 0%-9%) in the placebo arm (P <.0001). Additionally, experimental treatment yielded a mean active range of motion (ROM) change of 18.4% at week 25 compared with an improvement of 3.8% in the placebo arm (P = .0077).

Treatment-emergent adverse effects (TEAEs) were typically grade 1 or 2 in the vimseltinib arm, and investigators observed no signs of cholestatic hepatotoxicity, treatment-induced liver injury, or hair hypopigmentation. Serum enzyme elevations following treatment with vimseltinib were comparable with prior reports on the mechanism of action of CSF1R inhibitors. Overall, 6% of patients in the vimseltinib arm discontinued therapy due to TEAEs.

“The results from the MOTION pivotal phase 3 study provide compelling evidence that vimseltinib can address the unmet medical need in TGCT for an effective and well-tolerated therapy without cholestatic hepatotoxicity,” senior study author Hans Gelderblom, MD, PhD, chair of the Department of Medical Oncology at Leiden University Medical Center, said in a press release on these findings.² “In addition to its robust antitumor activity and tolerability, vimseltinib also demonstrated clinically significant functional and symptomatic improvements in key quality-of-life measures, which can provide long-term, meaningful benefits to [patients with] TGCT.”

References

1. 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. Ono Pharmaceutical, Co., Ltd. August 16, 2024. Accessed August 16, 2024. https://tinyurl.com/25zn6b96
2. Deciphera Pharmaceuticals announces oral presentation of results from MOTION pivotal phase 3 study of vimseltinib in patients with tenosynovial giant cell tumor (TGCT) at the 2024 ASCO Annual Meeting and online publication in The Lancet. News release. Deciphera Pharmaceuticals, Inc. June 3, 2024. Accessed August 16, 2024. https://tinyurl.com/3jp47bbs