Pune, India | November 10, 2025
Regeneron Pharmaceuticals recently announced encouraging Phase 2 trial outcomes for two investigational Factor XI antibodies, highlighting progress in clot-prevention therapies. The trials assessed the safety and effectiveness of REGN7508 and REGN9933 in patients undergoing unilateral total knee arthroplasty. Researchers shared the results at the American Heart Association Scientific Sessions 2025 and simultaneously published the findings in The Lancet.
REGN7508 binds to the catalytic domain of Factor XI, whereas REGN9933 targets the A2 domain, addressing different mechanistic pathways. Consequently, REGN7508 aims to deliver potent anticoagulation, while REGN9933 focuses on reducing bleeding risks. Therefore, clinicians may personalize treatment according to patient-specific risk profiles, potentially improving postoperative venous thromboembolism (VTE) prevention outcomes significantly.
In the ROXI VTE II trial, patients receiving REGN7508 experienced a VTE rate of 7.1%. The enoxaparin control group reported a rate of 20.6%. Similarly, the ROXI VTE I trial showed REGN9933 reduced VTE rates to 17.2%, compared with 22.2% for enoxaparin-treated patients. These findings clearly demonstrate that both antibodies substantially lower postoperative VTE rates, emphasizing their promise as effective antithrombotic therapies.
Importantly, neither trial observed major bleeding events or clinically relevant non-major bleeding, and adverse event rates remained similar across treatment and control groups. Postoperative anemia occurred in 7–13% of patients across both trial arms, suggesting a favorable safety profile. This differentiates these antibodies from conventional anticoagulants, which typically present higher bleeding risks, making Factor XI inhibition an attractive alternative.
Dr. Jeffrey I. Weitz, lead study author, highlighted Factor XI’s central role in postoperative VTE and explained that targeting distinct domains. It allows tailored treatment strategies for patients with variable clotting and bleeding risks. Additionally, REGN9933 provided the first clinical evidence of Factor XI activation. Factor XIIa contributes to postoperative venous thrombosis, offering valuable insight for developing future anticoagulation therapies beyond existing options.
Both Phase 2 trials were open-label and actively controlled, with treatments initiated 12–24 hours after surgery. ROXI VTE I compared REGN9933 against enoxaparin and apixaban, while ROXI VTE II compared REGN7508 against enoxaparin. By replacing standard anticoagulants with Factor XI antibodies, these therapies may offer safer alternatives for high-risk patients without compromising effective clot prevention.
Following the positive Phase 2 results, Regeneron has launched Phase 3 trials to evaluate broader patient populations. It includes individuals at risk for VTE in surgical and medical settings. Moreover, the company is exploring potential applications for stroke prevention in patients with atrial fibrillation, further expanding the clinical utility of Factor XI inhibition.
Additionally, Regeneron plans to host a virtual “Regeneron Roundtable” to update investors and stakeholders on the progress of its Factor XI antibody program. Analysts suggest these therapies could significantly reshape anticoagulation management, as traditional treatments often remain underutilized due to bleeding concerns. Targeted antibodies with high efficacy and low bleeding potential may improve patient outcomes while increasing clinical confidence.
The development of REGN7508 and REGN9933 underscores the growing emphasis on precision medicine within cardiovascular care. By selectively targeting specific clotting pathways, these biologics offer effective thromboembolism prevention without compromising safety, marking a shift from broad-spectrum anticoagulants. Furthermore, such innovations highlight the potential to customize therapies according to individual risk factors, improving overall treatment efficiency and patient satisfaction.
In summary, Regeneron’s Factor XI antibodies demonstrate robust antithrombotic efficacy and a strong safety profile. If Phase 3 trials validate these results, REGN7508 and REGN9933 could transform postoperative VTE prevention and expand applications into stroke and other thrombotic conditions. Over the next 12–24 months, regulatory reviews and additional trials will determine whether these therapies achieve widespread adoption, potentially setting new standards in anticoagulation care.
