Merck KGaA, Darmstadt, Germany, has secured U.S. Food and Drug Administration approval for Pimjetmi, or pimicotinib, as a once-daily oral treatment for adults with symptomatic tenosynovial giant cell tumour for whom surgical resection may cause worsening functional limitation or severe morbidity. The approval is based on the global Phase 3 MANEUVER study, in which 56% of patients receiving pimicotinib achieved an objective tumour response at Week 25 compared with 3.2% receiving placebo.
The regulatory decision gives Merck KGaA another foothold in rare-tumour oncology while turning a drug originally discovered by Abbisko Medicine Co., Ltd. into a commercial product across a fourth major jurisdiction. Pimjetmi was previously approved in China, Canada and Switzerland, and Merck KGaA holds worldwide commercialisation rights under a licensing agreement that could ultimately deliver up to US$605.5 million to Abbisko, including upfront, option and milestone payments, plus double-digit royalties on annual net sales.
The commercial opportunity is meaningful but should not be mistaken for an uncontested market. The United States already has Daiichi Sankyo Company, Limited’s Turalio, or pexidartinib, and Deciphera Pharmaceuticals’ Romvimza, or vimseltinib, approved for symptomatic TGCT in patients for whom surgery is not an acceptable solution. Pimjetmi therefore enters a treatment landscape in which efficacy, safety, convenience, physician familiarity and long-term tolerability will determine whether a strong Phase 3 response rate translates into meaningful uptake.
What did the Phase 3 MANEUVER trial establish about pimicotinib efficacy?
MANEUVER was a randomised, double-blind, placebo-controlled international Phase 3 trial enrolling patients with symptomatic TGCT whose disease was measurable and for whom surgery could result in dysfunction or serious complications. Participants were randomised two to one to receive pimicotinib 50 mg once daily or placebo, with geographic region used as a stratification factor.
The primary efficacy endpoint was objective response rate at Week 25 using RECIST version 1.1 and blinded independent central review. Pimicotinib achieved a 56% response rate, with a 95% confidence interval of 42% to 68%, compared with 3.2% for placebo. The difference was statistically significant and provided the central tumour-response evidence supporting FDA approval.
The durability data strengthen the result because tumour shrinkage did not appear to be restricted to brief responses. Median duration of response had not been reached at the regulatory analysis, while 91% of responders had maintained response for at least six months and 77% had maintained response for at least 12 months.
The trial also assessed outcomes beyond radiographic tumour reduction. Patients receiving pimicotinib experienced statistically significant improvements in active range of motion, worst pain and physical functioning compared with placebo, giving the regulatory package evidence that tumour response was accompanied by changes relevant to daily mobility and symptom burden.
That combination is particularly important in TGCT because radiographic reduction alone does not necessarily capture the practical value of therapy. A smaller tumour matters most clinically when it results in less pain, improved joint function or reduced interference with normal activity.
Why does TGCT require systemic treatment when it is usually not metastatic cancer?
Tenosynovial giant cell tumour is generally locally aggressive rather than conventionally metastatic. The disease develops around joints, tendon sheaths and bursae and can cause recurrent swelling, pain, stiffness and progressive loss of mobility even when it does not behave like a typical cancer that spreads throughout the body.
Surgery remains an important treatment when the tumour can be removed without unacceptable damage. The challenge arises in diffuse or anatomically difficult disease, where repeated operations can damage joints, nerves or surrounding structures and where complete removal may be difficult.
This is the population targeted by the Pimjetmi label. The FDA approval is specifically for adults with symptomatic disease for whom surgical resection may cause worsening functional limitation or severe morbidity, rather than every person diagnosed with TGCT.
The biological rationale for systemic treatment centres on colony-stimulating factor 1. TGCT commonly involves excessive CSF-1 signalling, attracting large numbers of CSF-1 receptor-expressing cells into the tumour microenvironment and contributing substantially to tumour mass and inflammation.
Pimicotinib is a small-molecule inhibitor of CSF-1R designed to disrupt that signalling pathway. Reducing recruitment and survival of those cells can shrink the tumour and potentially improve the symptoms caused by its physical and inflammatory effects.
Why do the pain and mobility findings matter alongside the 56% response rate?
TGCT can create a substantial quality-of-life burden despite its relatively low mortality risk. Tumours often develop near major joints, meaning even modest changes in size or inflammation can affect walking, bending, working, sleeping and other routine activities.
MANEUVER therefore included prespecified assessments of function and symptoms rather than relying exclusively on imaging. Pimicotinib produced statistically significant improvement in active range of motion, with the comparison against placebo reaching a p-value of 0.0003.
Patient-reported physical functioning also improved significantly, with a p-value of 0.0074, while worst pain improved with a p-value below 0.0001. Those outcomes provide a clinically relevant complement to the tumour-response endpoint because they address whether patients experienced functional changes during treatment.
They should not be interpreted as evidence that every responding patient returned to normal mobility or became pain-free. The magnitude of benefit can vary substantially depending on tumour location, joint damage, previous operations and how long disease has been present before systemic therapy begins.
Longer-term observation will also be important because structural joint damage may not reverse simply because tumour volume decreases. The strongest clinical value may ultimately come from reducing ongoing disease burden and preventing additional deterioration rather than restoring already lost function in every patient.
How does Pimjetmi fit alongside Romvimza and Turalio in the US TGCT market?
Pimjetmi is not the first FDA-approved systemic therapy for TGCT. Turalio received U.S. approval in 2019, while Romvimza was approved in February 2025 for adults with symptomatic TGCT for whom surgery could cause worsening functional limitation or severe morbidity.
Romvimza was supported by the randomised Phase 3 MOTION study, where vimseltinib produced a 40% objective response rate at Week 25 compared with no responses in the placebo group. The study also demonstrated significant improvements in range of motion, physical functioning and pain.
Pimjetmi’s 56% response rate appears numerically higher than the 40% reported with vimseltinib, but that comparison cannot establish superiority. MANEUVER and MOTION were separate trials conducted in different patients with differences in study execution, baseline characteristics and statistical context, so a head-to-head study would be required to determine whether one drug provides greater clinical benefit.
Turalio provides additional historical context but carries a different safety and access profile. Its prescribing information includes a boxed warning for serious and potentially fatal liver injury and requires distribution through a Risk Evaluation and Mitigation Strategy programme.
The presence of three systemic options could shift TGCT treatment from a question of whether to use systemic therapy toward a more nuanced choice among agents. Clinicians may increasingly consider response durability, liver safety, dosing frequency, monitoring burden, patient comorbidities and prior treatment when selecting therapy.
Does Pimjetmi avoid the liver-safety problem associated with the earliest CSF-1R therapy?
Safety will be one of the most important components of Pimjetmi’s commercial differentiation. The FDA prescribing information includes a warning for hepatotoxicity, meaning liver-related risk remains relevant and patients will require appropriate laboratory monitoring.
The overall safety profile differs from the well-known cholestatic liver injury concern associated with pexidartinib, although cross-product comparisons should be made cautiously. Longer-term integrated pimicotinib data involving 158 patients found aminotransferase elevations among the frequently reported adverse events of clinical interest, but investigators reported no evidence of cholestatic hepatotoxicity or drug-induced liver injury during the analysed follow-up.
The FDA lists pruritus, rash, facial oedema, periorbital oedema, fatigue, nausea, headache and peripheral oedema among the most common adverse reactions occurring in more than 20% of patients. Frequently observed laboratory abnormalities included increased creatine phosphokinase, lactate dehydrogenase, aspartate aminotransferase, lipase, cholesterol, amylase and alanine aminotransferase.
Longer-term pooled data also show that tolerability is not trivial. Grade 3 or higher treatment-emergent adverse events occurred in 37.3% of the 158 patients included in an integrated Phase 1 and Phase 3 analysis, while treatment interruptions occurred in 60.1% and dose reductions in 20.9%.
Only 5.1% discontinued treatment because of treatment-emergent adverse events in that analysis, suggesting many toxicities could be managed without permanently stopping therapy. Whether that pattern remains consistent in broader routine use will become clearer through post-marketing experience.
Why could once-daily oral dosing matter commercially?
Pimjetmi is administered at 50 mg orally once daily with or without food. That schedule is straightforward for a chronic systemic treatment and could become relevant when patients and clinicians compare the practical burden of available therapies.
Romvimza is administered orally at 30 mg twice weekly with at least 72 hours between doses. Turalio has its own dosing and monitoring requirements, including liver testing and the restricted REMS distribution programme.
Convenience alone rarely determines oncology prescribing, particularly when meaningful differences in efficacy or safety exist. However, TGCT patients may remain on systemic treatment for long periods, making adherence, laboratory monitoring and day-to-day treatment burden relevant to persistence.
Merck KGaA will therefore need to position Pimjetmi around more than its response rate. The strongest commercial proposition is likely to combine once-daily administration, durable responses, patient-reported functional improvement and a safety profile that can be managed without the specific restricted distribution framework associated with Turalio.
Pricing and reimbursement will add another dimension once U.S. commercial availability expands. Rare-disease therapies can face intensive payer scrutiny, especially when several approved alternatives exist, making comparative evidence increasingly important even where head-to-head trials are unavailable.
What does the FDA approval mean for Abbisko’s global licensing strategy?
Pimicotinib represents a major validation event for Abbisko Medicine because the programme originated within the Chinese biotechnology company before being partnered with Merck KGaA. Abbisko initially granted Merck KGaA commercial rights across mainland China, Hong Kong, Macau and Taiwan in December 2023 while giving the German company an option for worldwide commercialisation rights.
The initial agreement delivered US$70 million upfront. Merck KGaA later exercised the global option, triggering an additional US$85 million payment and giving it exclusive worldwide commercialisation rights.
Across upfront, option, development and commercial milestone payments, Abbisko is eligible for as much as US$605.5 million. The biotechnology company is also entitled to double-digit royalties on annual net sales, meaning commercial success in the United States and other countries can create a continuing revenue stream beyond regulatory milestones.
The first U.S. commercial sale will trigger an additional milestone payment, although the amount has not been publicly disclosed. That payment should not be confused with the full remaining contingent value of the licensing agreement.
For Chinese biotechnology companies, the approval provides another example of internally discovered medicines progressing through multinational licensing into major Western markets. Abbisko retains an economic interest while Merck KGaA supplies the global commercial infrastructure required to launch a rare-tumour medicine across multiple jurisdictions.
Why is the fourth international approval strategically important for Merck KGaA?
Pimjetmi was first approved in China in December 2025, followed by Health Canada approval in June 2026 and Swissmedic approval in October. The United States becomes the fourth market to authorise the medicine.
The U.S., Canadian and Swiss regulatory reviews were conducted through Project Orbis, the FDA Oncology Center of Excellence initiative designed to facilitate collaboration among international regulators. Australia, Israel and the United Kingdom were also involved in the U.S. review process, while the European Medicines Agency participated as an observer.
Parallel review can shorten the time between decisions in different jurisdictions, although each regulator still makes an independent determination and one approval does not guarantee another. Merck KGaA therefore has an opportunity to build a geographically broader franchise if additional regulatory decisions are favourable.
The company’s shares closed at €151.60 on November 11, up 1.5% for the session and roughly 10% over the preceding month. The stock was also trading close to its 52-week high of €152.10, although the movement reflects multiple developments across Merck KGaA and cannot be attributed solely to Pimjetmi.
For a group with businesses spanning life science, healthcare and electronics, a single rare-tumour approval is unlikely to transform the entire valuation. Its strategic importance lies more in strengthening the healthcare portfolio and demonstrating the ability to source external innovation and carry it through global registration.
Could pimicotinib expand beyond TGCT?
Abbisko has explored pimicotinib in additional indications, including chronic graft-versus-host disease and advanced pancreatic cancer. These programmes reflect the broader biological role of CSF-1R signalling in immune regulation and the tumour microenvironment.
Success in TGCT does not establish efficacy in those diseases. The biological rationale, dosing, combination strategy and clinical endpoints differ substantially, and additional indications require independent evidence.
The approved TGCT programme nevertheless gives the molecule a commercially validated starting point. Revenue from a marketed indication can support broader lifecycle development while regulators and investigators accumulate more long-term safety information.
Merck KGaA also has rights to commercialise pimicotinib worldwide and options relating to development in additional indications under the partnership structure. Whether the company commits significant resources beyond TGCT will likely depend on the strength of clinical signals relative to competing immunology and oncology programmes.
What will determine whether Pimjetmi becomes a meaningful US TGCT franchise?
The FDA approval resolves the central regulatory risk but shifts attention toward treatment selection. Pimjetmi enters a market with established systemic options, so physicians will need to determine which patients are best suited to each CSF-1R-targeted therapy.
The MANEUVER evidence provides a strong starting point. More than half of treated patients achieved radiographic responses at Week 25, most responders maintained benefit for at least a year, and functional measures including pain and range of motion also improved significantly.
Safety and persistence will now become equally important. Oedema, rash, pruritus, laboratory enzyme abnormalities and liver monitoring requirements can influence treatment experience, particularly when therapy continues for months or years.
Real-world uptake will also depend on reimbursement, access and how easily specialists can compare three approved systemic options without direct head-to-head trials. Merck KGaA will need to persuade oncologists and orthopaedic tumour specialists that the combination of efficacy, durability, function and manageable toxicity justifies choosing Pimjetmi rather than merely adding another drug to the TGCT shelf.
The broader significance of the approval is therefore not that patients previously had no systemic treatment. It is that TGCT has moved rapidly from a disease with very limited non-surgical options to one with multiple targeted medicines capable of shrinking tumours and improving function.
Pimjetmi’s 56% response rate gives Merck KGaA a credible entry into that competition. The harder test begins after approval, when comparative clinical judgement, long-term safety and patient access determine whether a strong Phase 3 result can become durable commercial adoption.
