- Caplacizumab is a therapeutic nanobody and the first single-domain VHH antibody to gain approval from both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA).
- It is specifically designed to target von Willebrand factor (vWF), a key protein in the blood clotting process. Unlike conventional antibodies, caplacizumab is a small, humanized VHH fragment derived from camelid heavy-chain–only antibodies, giving it unique properties such as high stability, rapid tissue penetration, and efficient binding to its target.
- The drug is indicated for the treatment of acquired thrombotic thrombocytopenic purpura (aTTP), a rare, life-threatening autoimmune blood clotting disorder. In aTTP, unusually large vWF multimers cause excessive platelet aggregation, leading to the formation of microthrombi in small blood vessels. These clots can restrict blood flow to vital organs, resulting in severe complications or death if left untreated.
- Caplacizumab works by binding to the A1 domain of vWF, blocking its interaction with the platelet glycoprotein Ib (GPIb) receptor. This action inhibits platelet adhesion and reduces the formation of pathological clots, thereby protecting organ function.
- Caplacizumab is administered in combination with plasma exchange and immunosuppressive therapy. Treatment begins with a single intravenous dose before the first plasma exchange, followed by daily subcutaneous injections during plasma exchange and for an additional 30 days afterward. This regimen ensures continuous suppression of abnormal platelet aggregation while the underlying autoimmune cause is addressed.
- Marketed under the brand name Cablivi by Sanofi (originally developed by Ablynx), caplacizumab demonstrates the clinical potential of nanobody technology. Its approval has opened the door for further therapeutic development using VHH antibodies, highlighting their advantages in terms of manufacturing efficiency, molecular stability, and the ability to access otherwise difficult-to-reach molecular targets.
