ArticleProceedings of the National Academy of Sciences of the United States of America2026
Discovery and development of a bispecific antibody for the treatment of hemophilia.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
The 2026 Lasker~DeBakey Clinical Medical Research Award has been awarded to Kunihiro Hattori, Takehisa Kitazawa, and Tomoyuki Igawa (Chugai Pharmaceuticals, Tokyo, Japan) for invention of a bispecific antibody that joins blood clotting Factors IXa (FIXa) and X (FX), restoring deficient Factor VIII (FVIII) activity in patients with hemophilia A and preventing severe bleeding in this hereditary disorder. Starting from the 1960s, types of FVIII-replacement therapy remarkably improved on-demand hemostatic treatment for ongoing bleeds and enabled prophylactic reduction of bleeding episodes. However, these agents required burdensome intravenous infusions multiple times per week, and ~30% of patients developed neutralizing anti-FVIII antibodies (FVIII inhibitors). To address these unmet medical needs, in 2000, Hattori-a molecular and hematology biologist, Kitazawa-a hematology biologist and translational researcher, and Igawa-a biochemist and protein engineer, conceived, designed, and created over the span of 10 y a novel FVIII-mimetic. Instead of a native protein construct, they engineered a bispecific IgG antibody against FIXa and FX, circumventing the need for FVIII and enabling subcutaneous administration up to once per month. Importantly, they identified the biophysical requirements for the bispecific to mimic FVIII function effectively and safely, and their breakthrough protein engineering design made possible favorable pharmacokinetics and physicochemical properties with efficient manufacturability. Their collective research efforts demonstrate how imagination, determination, and multidisciplinary scientific research come together to improve patients' lives.
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