Regeneron Advances Two Factor XI Antibodies to Phase 3 After Positive Phase 2 Results

Regeneron Pharmaceuticals, Inc., a prominent biotechnology company based in Tarrytown, New York, announced promising Phase 2 outcomes for its new monoclonal antibodies, REGN7508 and REGN9933. These antibodies are aimed at different domains of Factor XI, a protein involved in blood clotting, and are under investigation for their potential to prevent thrombosis while minimizing bleeding risks. The company plans to initiate a Phase 3 program in 2025.

REGN7508 targets the catalytic domain of Factor XI to enhance anticoagulant effects while reducing bleeding risk. Meanwhile, REGN9933 focuses on the A2 domain, offering an alternative for patients at a high risk of bleeding who cannot use existing anticoagulants. The Phase 2 trials demonstrated notable antithrombotic effects for both antibodies, with no significant bleeding noted across any treatment groups.

Dr. George D. Yancopoulos, Regeneron's President and Chief Scientific Officer, expressed satisfaction with the results, stating that the antibodies showed clear antithrombotic efficacy alongside a favorable safety profile following a single convenient dose. The findings align with preclinical data, where REGN7508 showed prolonged clotting times, and REGN9933 demonstrated similar effects compared to other agents targeting Factor XI. Dr. Yancopoulos emphasized that these results, supported by genetic evidence, reinforce the strategy to target various domains of Factor XI to provide tailored therapeutic options for patients with diverse bleeding risk profiles.

The research was conducted through two open-label, active-controlled Phase 2 trials, named ROXI-VTE-I and ROXI-VTE-II, evaluating the antibodies for preventing venous thromboembolism (VTE) post-total knee arthroplasty. In the ROXI-VTE-I trial, participants received either a single intravenous dose of REGN9933, daily doses of enoxaparin, or twice-daily doses of apixaban until venography. In the ROXI-VTE-II trial, participants received a single IV dose of REGN7508 or daily enoxaparin. All treatments commenced 12 to 24 hours after surgery, aligning with the standard administration of active comparators.

A pooled analysis of VTE rates from both trials indicated that REGN7508 surpassed enoxaparin and was not inferior to apixaban in preventing VTE. REGN9933 was shown to be non-inferior to enoxaparin. All VTE events in the study were asymptomatic, except for one instance of a symptomatic pulmonary embolism in the apixaban group. The incidence of VTE events was lower with REGN7508 at 7% compared to 17% with REGN9933, 21% with enoxaparin, and 12% with apixaban. No significant instances of bleeding or other adverse events were observed with any of the treatments.

Regeneron is advancing the development of REGN7508 and REGN9933 in response to the growing need for effective thrombosis prevention therapies that do not carry a heightened bleeding risk. An estimated one in four deaths globally is attributed to thrombosis, highlighting the necessity for innovative treatments. Current anticoagulants are not widely used due to bleeding risks, and adherence to oral agents is often poor.

Regeneron leverages its VelocImmune technology to produce optimized fully human antibodies. This technology, developed over several decades, uses genetically engineered mice with a humanized immune system. It has been instrumental in creating numerous FDA-approved monoclonal antibodies, contributing significantly to Regeneron's portfolio.

In summary, the positive Phase 2 results for REGN7508 and REGN9933 underscore their potential as effective and safe antithrombotic treatments, paving the way for further clinical development in a Phase 3 program set for 2025.