Blog Details

Cybersecurity expert —
Neither scrutinize dose of MK-2060 outperformed placebo

by
Kristen Monaco, Senior Group Writer, MedPage Nowadays
June 6, 2025 • 3 min read

An investigational anticoagulant that targets component XI did no longer stop arteriovenous graft (AVG) thrombosis in power hemodialysis sufferers, per a placebo-managed part IIb trial.

In 502 sufferers with halt-stage kidney illness (ESKD) receiving hemodialysis by potential of AVG, time to a graft thrombosis occasion used to be no longer critically various for these 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) when put next with placebo in an design-to-kind out population, said Wolfgang Winkelmayer, MD, ScD, of Baylor School of Medication in Houston.

Median time to first AVG thrombosis occasion within the overall scrutinize population — defined as the sudden occlusion of the AVG requiring thrombectomy or thrombolysis or various medical evidence of AVG thrombosis confirmed by imaging, surgical treatment, or pathology — used to be 16.6 months over 32 months of follow-up, Winkelmayer defined at the European Renal Association (ERA) annual congress.

Administered intravenously, the monoclonal antibody MK-2060 has a “novel approach” to anticoagulation by blockading the activation of component XI to boot to the downstream exercise of activated protein. The FDA granted it mercurial song designation in August 2022.

Part XI inhibition offered a “promising” antithrombotic potential and can own higher security by uncoupling thrombosis from hemostasis, Winkelmayer identified sometime of a session of unhurried-breaking medical 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 chance of thromboembolic events, which carry high morbidity and mortality, he current. “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 persisted. “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 comparability trial, all contributors needed to be receiving hemodialysis or hemodiafiltration no no longer up to thrice per week for 3 or extra hours per session for inclusion. Additionally they needed to own former, most steadily functioning AVG for 4 weeks sooner than randomization.

Amongst 506 included adults, moderate age used to be 60.5 years, 52% were females, 55% were white, and time on hemodialysis used to be 5.3 years.

The scrutinize length used to be occasion-pushed, requiring 171 AVG thrombosis events. This final occasion used to be then followed by a 3-month security period. “The trial lasted longer than anticipated to accrue those 171 events,” said Winkelmayer.

In a sensitivity diagnosis restricted to on-therapy contributors censored 90 days after the final dose, time to first AVG thrombosis occasion also did no longer fluctuate between the groups.

For a secondary final result that blended the first plus all recurrent events, AVG thrombosis events also did no longer fluctuate 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 affected person-years happened within the three groups, respectively.

Time to first predominant thrombotic cardiovascular occasion, an exploratory final result, also wasn’t any various for the 6-mg community (HR 0.93, 95% CI 0.52-1.65) or 20-mg community (HR 1.13, 95% CI 0.63-2.02) versus the placebo community.

“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 attributable to of toxicity. Essentially the most general motive used to be due to death, followed by kidney transplant.

When put next with placebo, there used to be no inequity in time to first lethal bleeding or bleeding in a essential location for the 6-mg community (HR 1.33, 95% CI 0.84-2.11), nevertheless for the 20-mg community, it used to be critically higher (HR 1.74, 95% CI 1.11-2.73). Half of bleeding events were vascular entry events, nevertheless most were no longer essential, said Winkelmayer.

When non-essential bleeds were excluded, neither MK-2060 dose had a higher bleed chance when put next with placebo.