Durable liver-directed gene therapy with adeno-associated viral (AAV) vectors has proven difficult to achieve in patients with the bleeding disorder hemophilia A (coagulation factor VIII [FVIII] deficiency).1 Liver toxicity signified by liver enzyme elevations has occurred in as many as 87% of individuals in the first year. Cytotoxic T cell responses against the AAV5 capsid may occur but are unlikely to tell the entire story, as liver enzymes continued to rise in years 2–5 after dosing in 24%–40% of valoctocogene roxaparvovec phase 3 trial participants, while transgene expression declined year to year in most individuals.

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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.

Read the full paper: FVIII-containing platelets modulate immune responses and attenuate inhibitor development in hemophilia A mice