Pune, India | November 10, 2025
Regeneron Pharmaceuticals has announced encouraging Phase 2 clinical trial results for two investigational Factor XI antibodies. REGN7508 and REGN9933, advancing clot-prevention therapy development. These trials assessed safety and effectiveness in patients undergoing unilateral total knee arthroplasty. The data were presented at the 2025 American Heart Association Scientific Sessions and concurrently published in The Lancet.
REGN7508 targets the catalytic domain of Factor XI, while REGN9933 targets its A2 domain, addressing different mechanisms. REGN7508 is designed to provide strong anticoagulation, whereas REGN9933 aims to reduce bleeding risk. This mechanistic difference allows clinicians to customize treatment based on patient-specific clotting and bleeding risk factors. It potentially improves venous thromboembolism (VTE) prevention outcomes.
In the ROXI VTE II trial, REGN7508 treatment led to a VTE rate of 7.1%, significantly lower than the 20.6% rate seen with enoxaparin. Similarly, the ROXI VTE I trial showed a 17.2% VTE rate with REGN9933 compared to 22.2% for enoxaparin patients. These results demonstrate that both antibodies effectively reduce postoperative VTE, supporting their potential as safe and effective antithrombotic agents.
Notably, neither trial reported any major bleeding or clinically relevant non-major bleeding events, with adverse event rates comparable between treatment and control groups. Postoperative anemia incidence ranged from 7% to 13% across both arms. Such findings highlight a favorable safety profile, distinguishing these antibodies from standard anticoagulants, which often carry increased bleeding risks.
Dr. Jeffrey I. Weitz, lead author, emphasized Factor XI’s crucial role in postoperative VTE and explained how targeting distinct domains permits flexible treatment strategies tailored to individual patient risk. Furthermore, REGN9933’s data revealed for the first time that Factor XIIa-driven activation of Factor XI contributes significantly to postoperative venous thrombosis, a discovery that may inspire novel anticoagulation therapies beyond existing options.
Both ROXI VTE I and II trials used an open-label, active-controlled design, with treatment initiated 12 to 24 hours post-surgery. ROXI VTE I compared REGN9933 against enoxaparin and apixaban, while ROXI VTE II assessed REGN7508 against enoxaparin. By offering alternatives to current standard anticoagulants, these antibodies may provide safer options for high-risk patients while maintaining effective clot prevention.
Following these positive Phase 2 outcomes, Regeneron has initiated Phase 3 trials to evaluate broader patient populations, including individuals at risk for VTE in surgical and medical contexts. The company is also exploring applications in stroke prevention among atrial fibrillation patients, expanding the potential clinical use of Factor XI inhibition.
Additionally, Regeneron plans a virtual “Regeneron Roundtable” to update investors and stakeholders on progress in its Factor XI antibody program. Analysts predict these therapies have the potential to transform anticoagulation management, as current anticoagulants are often underused due to bleeding risks. Tailored therapies combining strong efficacy and low bleeding potential could markedly improve patient outcomes.
The development of REGN7508 and REGN9933 underscores rising interest in precision medicine within cardiovascular care. By selectively targeting clotting pathways, these biologics promise effective VTE prevention without increasing bleeding risk.
In conclusion, Regeneron’s Factor XI antibody approach shows robust antithrombotic efficacy with a favorable safety profile. If Phase 3 trials validate these results, the antibodies may revolutionize postoperative VTE prevention and extend clinical application. Regulatory review and expanded studies over the next 12 to 24 months will determine their clinical adoption and impact.
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