FDA Grants Priority Review to Vimseltinib in Tenosynovial Giant Cell Tumor

US FDA

The FDA has accepted and granted priority review to a new drug application (NDA) for vimseltinib (DCC-3014), a colony-stimulating factor 1 receptor (CSF1R)-directed therapy, for the treatment of patients with tenosynovial giant cell tumor (TGCT), according to a press release from Ono Pharmaceutical, which added that the regulatory body assigned a Prescription Drug User Fee Act goal date of February 17, 2025.¹

The NDA is supported by data from the phase 3 MOTION study (NCT05059262) which evaluated treatment with vimseltinib vs placebo in patients with TGCT. At the 2024 ASCO Annual Meeting, investigators shared that at week 25, patients treated with vimseltinib (n = 83) achieved a statistically significant and clinically meaningful overall response rate (ORR) of 40% (95% CI, 29%-51%; P < .0001) compared with 0% in patients treated with placebo (n = 40).^1,2

“Building upon positive results from the MOTION pivotal phase 3 study and following our recent announcement that [the] European Medicines Agency [EMA] review of the vimseltinib’s marketing authorization application [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 of Deciphera Pharmaceuticals, stated in a news release.¹

The EMA accepted the MAA for vimseltinib in July 2024, beginning the EMA’s centralized review process of the agent.^1,3 The regulatory submission and acceptance was also supported by data from the international, randomized, double-blind MOTION study.

TGCT is a rare, non-malignant tumor that forms in or near joints due to overexpression of CSF1, leading to inflammation and tissue damage. Surgery is the primary treatment, but these tumors often recur, necessitating new therapeutic options. Vimseltinib is an investigational drug designed to selectively inhibit CSF1R; the agent is thereby being investigated in the 2-part, placebo-controlled MOTION trial.¹

The trial enrolled patients at least 18 years of age with a confirmed diagnosis of symptomatic TGCT not amenable to surgery and no prior anti-CSF1/CSF1R therapy. Eligible patients were randomly assigned 2:1 to receive 30 mg of vimseltinib twice weekly or placebo for 24 weeks. During the open-label period of the trial patients were eligible to continue treatment with vimseltinib or cross over to receive vimseltinib if they had been assigned to the placebo arm.^1,2

The primary end point of the MOTION trial was ORR by independent radiological review (IRR) using RECIST 1.1 criteria at week 25; secondary end points included IRR-assessed ORR by tumor volume score (TVS), change from baseline in active range of motion, and patient-reported outcomes.

Additional results from the trial indicated that the agent demonstrated robust and statistically significant antitumor activity by TVS, with an ORR of 67% (95% CI, 56%-77%) vs 0% with placebo (P < .0001). The median duration of response (DOR) with vimseltinib using RECIST 1.1 criteria was not reached ([NR] range, 0.03+ to 11.7+ months) and the median DOR using TVS was also NR (range, 0.03+ to 13.9+ months).

Vimseltinib also demonstrated statistically significant and clinically meaningful improvements vs placebo across all key secondary end points. From baseline the agent led to improvements in active range of motion (18.4% vs 3.8%; difference, 14.6%; P = .0077), as well as PROMIS-Physical Function (mean change, 4.6 vs 1.3; difference, 3.3; P = .0007). Additionally, vimseltinib led to improvements in worst stiffness Numeric Rating Scale (mean change, –2.1 vs –0.3; difference, –1.8; P < .0001), EQ-Visual Analogue Scale (mean change, 13.5 vs 6.1; difference, 7.4; P = .0155), and Brief Pain Inventory (40% vs 9%; difference, 26%; P = .0056).

Vimseltinib also demonstrated a manageable safety profile that was well tolerated. The most common treatment-emergent adverse effects (TEAEs) included periorbital edema (all grade, 45%; grade 3/4, 4%), fatigue (33%; 0%), face edema (31%; 1%), pruritus (29%; 2%), and headache (28%; 1%). Notably, there was no evidence of cholestatic hepatotoxicity, drug-associated liver injury, or hair/skin hypopigmentation.

TEAEs resulted in treatment discontinuation in 6% of patients who received vimseltinib.

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, Ltd. August 16, 2024. Accessed August 16, 2024. https://www.ono-pharma.com/en/news/20240816.html
2. Tap WD, Bhadri V, Stacchiotti S, et al. Efficacy, safety, and patient-reported outcomes of vimseltinib in patients with tenosynovial giant cell tumor: results from the phase 3 MOTION trial. J Clin Oncol. 2024;42(suppl 16):11500. doi:10.1200/JCO.2024.42.16_suppl.11500
3. European Medicines Agency accepts Deciphera’s marketing authorization application for vimseltinib for treatment of patients with tenosynovial giant cell tumor (TGCT). News release. Ono Pharmaceutical, Ltd. July 19, 2024. Accessed August 16, 2024. https://www.ono-pharma.com/en/news/20240719.html