Sanofi Strengthens Hemophilia Treatment Portfolio With Breakthrough Clinical Data on Dual Therapeutic Candidates

Sanofi has unveiled compelling clinical evidence reinforcing its position in rare blood disorders at the 32nd ISTH Congress, with significant advancements across its hemophilia pipeline. The company showcased comprehensive data from two investigational therapies—the once-weekly factor VIII therapy and the first-in-class antithrombin inhibitor—alongside regulatory progress that signals accelerating timelines for patient access.

Clinical Efficacy Data Demonstrates Sustained Bleed Protection

The long-term XTEND-ed phase 3 extension study presented critical efficacy benchmarks for Sanofi’s lead hemophilia A candidate. In adults and adolescents aged 12 and older who had previously enrolled in the pivotal XTEND-1 trial, the treatment maintained a mean annualized bleed rate (ABR) of 0.72 to 0.42 across study arms, representing robust and sustained prophylactic coverage. Notably, the pediatric population demonstrated comparable safety and efficacy, with a mean ABR of 0.70—consistent with earlier phase 3 findings—and zero incidence of factor VIII inhibitor development.

Beyond bleed prevention, joint health outcomes provided additional reassurance. Over a two-year observation period, adult and adolescent patients receiving once-weekly prophylaxis showed either improvement or maintenance of joint integrity as measured by standardized hemophilia joint health scoring methodologies. This sustained joint protection addresses a critical unmet need, as progressive joint damage represents a long-term morbidity burden in hemophilia populations.

Perioperative Safety and Surgical Efficacy

One of the most clinically significant datasets involved perioperative management. Across 49 major surgical procedures performed in 41 patients from the XTEND clinical program, hemostasis was consistently maintained in 100% of procedures. Hemostatic response was rated as excellent in 43 of 49 surgeries, establishing perioperative efficacy that matches or exceeds current standard-of-care options.

The antithrombin-based inhibitor candidate similarly demonstrated surgical viability, with 60 major surgical procedures safely completed in its clinical development program. Notably, 24 of these procedures involved patients with inhibitors—a historically high-risk population—yet all major surgeries were conducted without thrombotic complications and in accordance with standard bleed management protocols.

Safety Profile Refinement and Thrombotic Risk Mitigation

The revised antithrombin-based dosing regimen for the first-in-class therapy has meaningfully enhanced its safety architecture. Under the optimized dosing approach targeting antithrombin activity levels between 15-35%, the clinical program observed marked reductions in thrombotic events with substantially extended drug exposure. Additionally, hepatobiliary complications were substantially reduced, with elevations in liver transaminases being infrequent and self-resolving, and cholecystitis or gallstone events resolving without clinical sequelae or treatment discontinuations.

Regulatory Progress Accelerates Patient Access Timeline

In a significant regulatory milestone, Sanofi’s antithrombin inhibitor candidate received FDA acceptance for a New Drug Application with a PDUFA target action date of March 28, 2025. This compressed regulatory timeline follows Breakthrough Therapy Designation granted in December 2023 for hemophilia B with inhibitors. Parallel regulatory submissions have been filed in China and Brazil, positioning the candidate for potential near-term market authorization across multiple geographies.

Dietmar Berger, Chief Medical Officer and Global Head of Development, emphasized the broader clinical significance: “These data underscore the critical importance of treatment options that deliver consistent outcomes across diverse clinical scenarios—from routine prophylaxis to major surgery—and can sustain benefit throughout a patient’s lifetime. Our engagement with regulatory partners reflects our commitment to translating these clinical advances into meaningful patient access.”

Breakthrough Innovation in Extended Half-Life Factor Replacement

Sanofi’s lead hemophilia A therapy represents a paradigm shift in factor VIII replacement. The technology incorporates von Willebrand factor and XTEN polypeptide architecture, enabling a 3- to 4-fold extension in half-life relative to conventional and extended half-life alternatives, the first factor VIII candidate to overcome the inherent von Willebrand factor ceiling that constrains other therapies. Once-weekly dosing now maintains factor activity within normal to near-normal ranges throughout the prophylactic interval.

The innovation has garnered regulatory recognition, including FDA Breakthrough Therapy Designation (May 2022), Fast Track Designation (February 2021), and Orphan Drug Designation (2017). The European Commission approved the candidate in June 2024 for bleed prevention and perioperative prophylaxis under an alternative commercial designation, expanding its authorized geographic footprint.

Implications for Hemophilia Care Paradigms

Collectively, these data address longstanding clinical challenges in hemophilia management: the frequency of prophylactic dosing, the heterogeneity of patient responses, perioperative safety in inhibitor-positive populations, and long-term joint preservation. The dual portfolio expansion reflects Sanofi’s strategic positioning to provide complementary treatment mechanisms—traditional factor replacement optimized for extended coverage alongside novel inhibitor-based prophylaxis—offering flexibility across the full spectrum of hemophilia A and B populations.