Regeneron Two-Factor XI Antibodies Demonstrate Antithrombotic Effects

Pune, India | November 10, 2025

Regeneron Pharmaceuticals announced positive Phase 2 trial results for two investigational Factor XI antibodies, marking progress in clot-prevention therapies. The trials evaluated the safety and efficacy of REGN7508 and REGN9933 in patients undergoing unilateral total knee arthroplasty. Researchers presented the findings at the American Heart Association Scientific Sessions 2025 and simultaneously published them in The Lancet.

REGN7508 targets the catalytic domain of Factor XI, while REGN9933 focuses on the A2 domain. Each antibody addresses distinct mechanistic pathways. REGN7508 aims to provide strong anticoagulation, whereas REGN9933 minimizes bleeding risks. Therefore, clinicians may personalize therapy based on patient-specific risk, improving VTE prevention outcomes.

In the ROXI‑VTE‑II trial, patients treated with REGN7508 had a VTE rate of 7.1%, compared with 20.6% in the enoxaparin control group. Similarly, the ROXI‑VTE‑I trial showed that REGN9933 achieved a 17.2% VTE rate, while enoxaparin patients had 22.2%. These results demonstrate that both antibodies substantially reduce postoperative VTE, highlighting their potential as effective antithrombotic therapies.

Neither trial reported major bleeding events or clinically relevant non-major bleeding. Adverse event rates were similar across treatment and control groups. Postoperative anemia occurred in 7–13% of patients across trial arms. These findings suggest a favorable safety profile and differentiate these antibodies from traditional anticoagulants, which often carry higher bleeding risks.

Dr. Jeffrey I. Weitz, lead study author, emphasized that Factor XI plays a critical role in postoperative VTE. He explained that targeting distinct domains allows flexible treatment strategies for patients with different clotting and bleeding risks. Furthermore, REGN9933 demonstrated for the first time that activation of Factor XI through Factor XIIa contributes to postoperative venous thrombosis. This insight could enable new anticoagulation therapies beyond current options.

Both trials were open-label and actively controlled, with treatment starting 12–24 hours after surgery. ROXI‑VTE‑I compared REGN9933 against enoxaparin and apixaban, while ROXI‑VTE‑II compared REGN7508 against enoxaparin. By transitioning from standard anticoagulants, these antibodies may provide safer alternatives for high-risk patients while maintaining effective clot prevention.

Following these positive Phase 2 results, Regeneron has initiated Phase 3 trials to study broader patient populations, including those at risk for VTE in surgical and medical settings. The company also explores potential applications in stroke prevention for patients with atrial fibrillation, expanding the clinical utility of Factor XI inhibition.

Additionally, Regeneron plans to host a virtual “Regeneron Roundtable” to update investors and stakeholders about progress in its Factor XI antibody program. Analysts predict that these therapies could transform anticoagulation management. Traditional anticoagulants are often underutilized due to bleeding risks, whereas tailored therapies with strong efficacy and low bleeding potential may improve patient outcomes.

The development of REGN7508 and REGN9933 also underscores the growing focus on precision medicine in cardiovascular care. By targeting specific clotting pathways, these biologics provide effective prevention without compromising safety.

In summary, Regeneron’s approach to Factor XI inhibition demonstrates strong antithrombotic efficacy and a favorable safety profile. If Phase 3 trials confirm these outcomes, these antibodies could transform postoperative VTE prevention and broaden clinical applications. Over the next 12–24 months, regulatory review and expanded trials will determine whether these therapies achieve widespread clinical adoption.