Novel Anticoagulant Flops for Staving Off Graft Thrombosis in Dialysis Patients

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Neither study dose of MK-2060 outperformed placebo

by
Kristen Monaco, Senior Staff Writer, MedPage Today
June 6, 2025 • 3 min read

An investigational anticoagulant that targets factor XI failed to prevent arteriovenous graft (AVG) thrombosis in chronic hemodialysis patients, according to a placebo-controlled phase IIb trial.

In 502 patients with end-stage kidney disease (ESKD) receiving hemodialysis via AVG, time to a graft thrombosis event was not significantly different for those on 6 mg of MK-2060 (HR 0.83, 95% CI 0.58-1.19) or 20 mg of MK-2060 (HR 0.87, 95% CI 0.60-1.26) compared with placebo in an intention-to-treat population, said Wolfgang Winkelmayer, MD, ScD, of Baylor College of Medicine in Houston.

Median time to first AVG thrombosis event in the overall study population — defined as the sudden occlusion of the AVG requiring thrombectomy or thrombolysis or other clinical evidence of AVG thrombosis confirmed by imaging, surgery, or pathology — was 16.6 months over 32 months of follow-up, Winkelmayer explained at the European Renal Association (ERA) annual congress.

Administered intravenously, the monoclonal antibody MK-2060 has a “novel approach” to anticoagulation by blocking the activation of factor XI as well as the downstream activity of activated protein. The FDA granted it fast track designation in August 2022.

Factor XI inhibition presented a “promising” antithrombotic approach and may have better safety by uncoupling thrombosis from hemostasis, Winkelmayer pointed out during a session of late-breaking clinical trials. “All I can say is perhaps further research is needed to understand how factor XI inhibition can be useful and of utility in patients with ESKD receiving hemodialysis.”

Patients with kidney failure receiving hemodialysis are at very high risk of thromboembolic events, which carry high morbidity and mortality, he noted. “There’s this subset of hemodialysis patients that rely on an AVG graft, and they have high rates of access failure and these access failure events usually manifest themselves as AVG thrombosis.”

“In the general population, there are anticoagulants, which reduce thromboembolic risk and provide a net benefit relative to increased bleeding risk in many indications,” Winkelmayer continued. “But there are concerns in regards to anticoagulation in the ESKD population due to further elevated bleeding risk because these patients have uremia-related platelet and endothelial dysfunction.”

“There are concerns with appropriate dosing in this population, and at the end of the day, there’s really a lack of high-level evidence specific in the ESKD population,” he said.

For this double-blind, two-dose comparison trial, all participants had to be receiving hemodialysis or hemodiafiltration at least three times per week for 3 or more hours per session for inclusion. They also had to have mature, normally functioning AVG for 4 weeks prior to randomization.

Among 506 included adults, average age was 60.5 years, 52% were women, 55% were white, and time on hemodialysis was 5.3 years.

The study duration was event-driven, requiring 171 AVG thrombosis events. This final event was then followed by a 3-month safety period. “The trial lasted longer than anticipated to accrue those 171 events,” said Winkelmayer.

In a sensitivity analysis restricted to on-treatment participants censored 90 days after the last dose, time to first AVG thrombosis event also did not differ between the groups.

For a secondary outcome that combined the first plus all recurrent events, AVG thrombosis events also didn’t differ between the 6-mg dose (HR 0.93, 95% CI 0.71-1.24) or 20-mg dose of MK-2060 (HR 0.91, 95% CI 0.68-1.12) and placebo. A total of 38.03, 38.95, and 42.97 events/100 patient-years occurred in the three groups, respectively.

Time to first major thrombotic cardiovascular event, an exploratory outcome, also wasn’t any different for the 6-mg group (HR 0.93, 95% CI 0.52-1.65) or 20-mg group (HR 1.13, 95% CI 0.63-2.02) versus the placebo group.

“Almost everybody had an adverse event,” said Winkelmayer, and 15.2%, 18.8%, and 16.1% of the 6-mg, 20-mg, and placebo groups discontinued because of toxicity. The most common reason was due to death, followed by kidney transplant.

Compared with placebo, there was no difference in time to first fatal bleeding or bleeding in a critical site for the 6-mg group (HR 1.33, 95% CI 0.84-2.11), but for the 20-mg group, it was significantly higher (HR 1.74, 95% CI 1.11-2.73). Half of bleeding events were vascular access events, but most were not serious, said Winkelmayer.

When non-serious bleeds were excluded, neither MK-2060 dose had a higher bleed risk compared with placebo.