Pimicotinib Gives Tenosynovial Giant Cell Tumor a Third Oral Drug, and the First Taken Once a Day
The FDA approved pimicotinib on Nov. 10 after a 56 percent week-25 response rate, the third CSF-1R inhibitor for TGCT and the only one dosed daily.
Idea in Brief
The Approval
On Nov. 10 the FDA approved pimicotinib (Pimjetmi, EMD Serono) 50 mg once daily for adults with symptomatic TGCT when surgery may worsen function or cause severe morbidity.
The Evidence
In MANEUVER (94 patients), the week-25 response rate was 56 percent on pimicotinib and 3.2 percent on placebo by blinded central review.
The Caveats
The trial is small with a 24-week placebo phase, hepatotoxicity is a labeled warning, and no U.S. price has been published.
Fifty-six percent of patients with tenosynovial giant cell tumor who took pimicotinib had a tumor response at week 25, against 3.2 percent on placebo. On that result, the Food and Drug Administration on Nov. 10 approved pimicotinib (Pimjetmi, EMD Serono), a once-daily oral CSF-1R inhibitor, for adults with symptomatic disease when surgery may worsen function or cause severe morbidity.
It is the third drug in the class cleared for the tumor in the United States, after pexidartinib (Turalio, Daiichi Sankyo) in 2019 and vimseltinib (Romvimza, Deciphera) on Feb. 14, 2025, by the FDA's approval notice and the earlier labels. For orthopedic surgeons and the oncologists who share these patients, the comparison that matters most is dosing, liver monitoring and what each label demands of the prescriber, more than which response rate is highest.
What the trial showed
MANEUVER (NCT05804045) was a double-blind, placebo-controlled phase 3 trial run by Abbisko Therapeutics, which developed the drug. It randomized 94 patients 2:1 to pimicotinib 50 mg daily (63 patients) or placebo (31) for 24 weeks, at 40 sites in seven countries, including the United States, Canada, China and four European countries. Patients needed at least one measurable lesion of 2 cm or more and no prior anti-CSF-1 or CSF-1R therapy. Randomization was stratified by China versus elsewhere, and 45 of the 94 patients were enrolled in China, according to EMD Serono's announcement.
The primary endpoint was overall response rate by blinded independent central review under RECIST 1.1: 56 percent (95% CI, 42 to 68) on pimicotinib and 3.2 percent (95% CI, 0.1 to 17) on placebo. Range of motion of the affected joint, worst pain and PROMIS physical function all improved significantly at week 25. Median duration of response was not reached; 91 percent of responders kept the response for at least six months and 77 percent for at least 12, the FDA said.
How the three CSF-1R inhibitors compare
We set the three U.S. labels and pivotal trials side by side. The trials enrolled different patients at different times, so the response rates are not a head-to-head comparison.
| Pexidartinib (Turalio) | Vimseltinib (Romvimza) | Pimicotinib (Pimjetmi) | |
|---|---|---|---|
| U.S. approval | 2019 | Feb. 14, 2025 | Nov. 10, 2026 |
| Pivotal trial | ENLIVEN, 61 vs 59 | MOTION, 83 vs 40 | MANEUVER, 63 vs 31 |
| Response at week 25, drug vs placebo | 38% vs 0% | 40% vs 0% | 56% vs 3.2% |
| Dose | 250 mg twice daily with a low-fat meal | 30 mg twice weekly, at least 72 hours apart | 50 mg once daily, with or without food |
| Doses a year, our arithmetic | 730 | about 104 | 365 |
| Liver | Boxed warning, including vanishing bile duct syndrome | Warning: AST and ALT elevations | Warning: hepatotoxicity |
| Restricted distribution | Yes, Turalio REMS | No | None described in the FDA notice |
By our count, 634 days separate the vimseltinib and pimicotinib approvals, and MANEUVER reached its primary completion date on Sept. 23, 2024, 778 days before the U.S. approval. China approved the drug in December 2025, and Health Canada and Swissmedic followed in June and October 2026, EMD Serono said.
With three CSF-1R inhibitors on the market, the choice will turn on the liver label and the dosing schedule as much as on the week-25 response rate.
Clinical Pearls
- MANEUVER randomized 94 patients 2:1 to pimicotinib 50 mg daily or placebo for 24 weeks; 45 were enrolled in China.
- Overall response at week 25 was 56 percent (95% CI, 42 to 68) vs 3.2 percent (95% CI, 0.1 to 17).
- Of responders, 91 percent kept the response at least six months and 77 percent at least 12 months.
- Warnings: hepatotoxicity, embryo-fetal toxicity and serum creatinine increases without an effect on renal function.
- EMD Serono's patient information calls for liver tests at baseline, monthly for three months, then every three months through year one.
- Pexidartinib alone carries a boxed liver warning and a REMS; vimseltinib is dosed twice weekly.
The liver signal
Hepatotoxicity is the class problem. Pexidartinib's label carries a boxed warning for serious and potentially fatal liver injury, including vanishing bile duct syndrome, and it is available only through a REMS program that certifies prescribers and pharmacies and enrolls patients, according to the Turalio label. Vimseltinib's Romvimza label lists elevated AST and ALT as a warning, with liver tests before and during treatment, and no boxed warning.
Pimicotinib's warnings are hepatotoxicity, embryo-fetal toxicity and increased serum creatinine without an effect on renal function, the FDA said. EMD Serono's patient information calls for liver blood tests before starting, monthly for the first three months, every three months for the rest of the first year and as needed after that. The company says MANEUVER showed no evidence of cholestatic hepatotoxicity or hair and skin hypopigmentation. That is the sponsor's statement from one 94-patient trial, not an FDA conclusion, and laboratory abnormalities in more than 30 percent of patients included increased creatine phosphokinase, lactate dehydrogenase, AST, lipase, cholesterol, amylase and ALT.
Adverse reactions in more than 20 percent of patients were pruritus, rash, face and periorbital edema, fatigue, nausea, headache and peripheral edema. In the blinded phase, side effects led one patient (1.6 percent) to stop the drug and five (7.9 percent) to reduce the dose, EMD Serono said.
Caveats
MANEUVER is small, and its placebo phase lasted 24 weeks. Nearly half its patients came from China, where the drug was developed, and the FDA's review ran under Project Orbis with Australia, Canada, Israel, Switzerland and the United Kingdom. The trial is still active, with study completion estimated for June 2028 on its registry record, so long-term liver safety and what happens after stopping the drug are not yet known. The approval notice gives no U.S. price, and neither does the company.
The approval came a day after the FDA cleared asundexian for secondary stroke prevention. The prescribing question is similar to the one we described for the two ESR1 approvals: drugs with the same target and different monitoring burdens.
What it means in clinic
Tenosynovial giant cell tumor is usually managed surgically, and these drugs are for the patients whose surgery would cost them function. For those patients there are now three oral options, and only pexidartinib requires REMS enrollment, based on what the FDA has published so far. Before prescribing pimicotinib, build the liver test schedule into the order set, confirm contraception plans, since the label warns of fetal harm, and expect serum creatinine increases that the FDA says do not affect renal function. Expect prior authorization, and document in the chart why resection is not the better choice.
Reported, fact-checked and edited by The Script Pad's editorial staff. See How we use AI.
This article is for professional education and does not replace clinical judgment. Treatment decisions should be based on the individual patient and current guidelines.
