FXI Inhibitors Reduce Venous Thrombosis Risk After Central Catheter Insertion

Amrecibart and cenvacibart both substantially reduced venous thrombosis rates after peripherally inserted central catheter (PICC) use, according to new data from the ROXI-CATH trial.1

These data were presented at the American Heart Association (AHA) Scientific Sessions 2026 in Chicago, Illinois, by Gregory Piazza, MD, MS, a cardiovascular medicine specialist at Brigham and Women’s Hospital and an associate professor of medicine at Harvard Medical School.1

“In practice, in the setting of long-term indwelling catheter device leads, we see quite often that when patients develop thrombosis, it can interrupt their therapy,” Piazza told HCPLive in an exclusive interview. “It can interrupt their chemotherapy, their nutrition, or their antibiotics. Factor XI is the first real sign of promise that we have for preventing contact-mediated thrombosis.”

ROXI-CATH was a phase 2 randomized, double-blind, placebo-controlled study evaluating the efficacy of amrecibart 300 mg (REGN9933) and cenvacibart 250 mg (REGN7508) versus placebo in patients undergoing a PICC placement. The trial enrolled patients with a clinical indication for PICC of ≤14 days, a body weight ≥45 kg and ≤130 kg during screening, and international normalized ratio (INR) and aPTT values at or below the upper limit of normal, among other criteria. Patients with unsuccessful PICC placement, a history of prior venous thrombosis in the arm, or peripheral catheters in the same arm, among other criteria, were excluded.2

Eligible patients were randomly assigned in a 1:1:1 ratio to receive a single intravenous dose of either amrecibart, cenvacibart, or placebo. The study included 3 primary endpoints, which were incidence of confirmed thrombosis, incidence of treatment-emergent adverse events (TEAEs), and severity of TEAEs. Key secondary outcomes included incidence of confirmed PICC-associated venous thrombosis, incidence of major bleeding, and concentrations of either amrecibart or cenvacibart in serum by day 75.2

Piazza and colleagues included a total of 194 patients in the full analysis set. Among these patients, mean age was 58 years and 61.9% had active cancer. By day 14, adjudicated venous thrombosis events occurred in 13 of 65 (20%) patients receiving amrecibart (odds ratio [OR], 0.37; 90% CI, 0.18-0.65) and 13 of 66 (19.7%) patients receiving cenvacibart (OR, 0.36; 90% CI, 0.17-0.64), compared to 27 of 63 (42.9%) patients in the placebo arm.1

Additionally, TEAEs occurred in 45/65, 42/66, and 48/63 patients in the amrecibart, cenvacibart, and placebo arms, respectively. No patients exhibited major bleeding during the study period. Clinically relevant nonmajor bleeding occurred in 2 patients in each arm, and 1 patient in the cenvacibart arm developed an acute traumatic subdural hemorrhage on day 28, dying on day 31. Another 5 deaths unrelated to thrombosis occurred across all treatment arms.1

Ultimately, Piazza and colleagues concluded that a single infusion of either amrecibart or cenvacibart effectively reduced venous thrombosis event rates after PICC insertion, indicating FXI’s potential role as a novel antithrombotic strategy for contact-mediated thrombosis.1

“It’s really fascinating what we’re seeing with factor XI and these different agents,” Piazza said. “I think all of these agents have nuances about them that could make them preferable in one area versus another. In some of the other agents that have been tested, there is variability in how much factor XI inhibition they produce, but in ROXI-CATH we saw really profound inhibition, which I think gave us the strong results in efficacy.”

Editors’ Note: Piazza reports disclosures with Bristol Myers Squibb/Pfizer, Janssen, Bayer, Amgen, Regeneron, Alexion, and others.

References

1. Zwicker J, Kithart A, Kaplan J, et al. Amrecibart and Cenvacibart for the Prevention of Catheter-Related Thrombosis: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Trial (ROXI-CATH). Presented at the American Heart Association (AHA) Scientific Sessions 2026, Chicago, IL. November 6-9, 2026.

2. Regeneron Pharmaceuticals. A Trial to Learn How Well REGN9933 and REGN7508 Work for Preventing Blood Clots, and How Safe They Are, in Adults Who Have a Peripherally Inserted Central Catheter (PICC) (ROXI-CATH). ClinicalTrials.gov Identifier: NCT06299111. Updated April 13, 2026. Accessed November 7, 2026. https://clinicaltrials.gov/study/NCT06299111?term=NCT06299111&rank=1