Regeneron Pharmaceuticals has announced positive Phase 2 results for two innovative monoclonal antibodies targeting distinct domains of Factor XI. REGN7508, designed to maximize anticoagulant activity while minimizing bleeding risk, targets the catalytic domain, while REGN9933, aimed at patients with the highest bleeding risk, focuses on the A2 domain. Both antibodies demonstrated robust antithrombotic effects without any clinically relevant bleeding observed in the treatment arms.
“Our Factor XI antibodies targeting the catalytic and A2 domains were rigorously evaluated alongside current standards of care and showed clear evidence of antithrombotic effect with an encouraging safety profile after a convenient single dose,” said George D. Yancopoulos, M.D., Ph.D., Board Co-Chair, President, and Chief Scientific Officer at Regeneron. “These Phase 2 results, coupled with preclinical data, demonstrate the potential of REGN7508 and REGN9933 to provide tailored therapies for patients with varying bleeding risk profiles across diverse treatment settings. We are excited to advance these candidates into a comprehensive Phase 3 program starting in 2025.”
Phase 2 Trials Overview
Regeneron conducted two open-label, active-controlled Phase 2 trials, ROXI-VTE-I and ROXI-VTE-II, to assess the efficacy and safety of REGN7508 and REGN9933 for preventing venous thromboembolism (VTE) following unilateral total knee arthroplasty. Both trials were conducted at the same centers under similar protocols.
In ROXI-VTE-I, participants received either a single intravenous (IV) dose of REGN9933, daily enoxaparin, or twice-daily doses of apixaban until venography. In ROXI-VTE-II, participants received a single IV dose of REGN7508 or daily enoxaparin until venography. Unlike other trials evaluating Factor XI antibodies, all treatments in these studies began 12 to 24 hours post-surgery, aligning with the approved administration of the active comparators.
Key Findings
A pooled analysis of the trials revealed:
- REGN7508: Demonstrated superiority to enoxaparin and non-inferiority to apixaban in reducing VTE rates at venography.
- REGN9933: Showed non-inferiority to enoxaparin.
Notably, all VTE events were asymptomatic, except for one symptomatic pulmonary embolism case in the apixaban arm. There were no instances of major bleeding, clinically relevant non-major bleeding, or surgical site bleeding in any treatment arm. The only treatment-related adverse event was a case of minimal bleeding (contusion) reported in the enoxaparin arm of ROXI-VTE-I.
Safety Profile
Both REGN7508 and REGN9933 were well-tolerated, with no treatment-related serious adverse events (SAEs) reported. Additionally:
- No adverse events (AEs) led to trial discontinuation, dose interruption, or modification in any arm.
- No deaths or adverse events of special interest were recorded.
- AE rates were generally similar across all treatment groups.
Broader Implications
Preclinical data support the clinical findings, showing that REGN7508 prolonged activated partial thromboplastin clotting time more effectively, while REGN9933 demonstrated similar efficacy compared to other Factor XI-targeted agents. These results, alongside compelling genetic evidence, underscore the potential of targeting distinct domains of Factor XI to tailor therapies for diverse patient needs.
Regeneron’s Phase 2 data strengthen its confidence in advancing REGN7508 and REGN9933 to a broad Phase 3 program. The company aims to address unmet needs in anticoagulation therapy by offering innovative, domain-specific solutions for patients with varying bleeding risk profiles. The Phase 3 program is scheduled to commence in 2025, marking a significant step forward in the development of next-generation anticoagulant therapies.
