The first nanobody therapy to treat adults with acquired thrombotic thrombocytopenic purpura (TTP) has been named Drug Discovery of the Year 2020 by the British Pharmacological Society.
The award recognises the novel mode of action of caplacizumab, which is an anti-von Willebrand factor humanised, bivalent variable-domain-only immunoglobulin fragment, that inhibits interaction between von Willebrand factor multimers and platelets. It has been shown to have an immediate effect on platelet adhesion.
The result from the HERCULES trial published earlier this year in the New England Journal of Medicine showed that caplacizumab was associated with faster normalisation of platelet count; a lower incidence of a composite of TTP-related death, recurrence of TTP or a thromboembolic event; and a lower rate of recurrence of TTP than placebo.
In the double-blind, controlled trial, 145 patients with TTP were randomly assigned to receive caplacizumab (10 mg intravenous loading bolus, followed by 10 mg daily subcutaneously) or placebo during plasma exchange and for 30 days thereafter.
The median time to normalisation of the platelet count was shorter with caplacizumab than with placebo (2.69 days vs 2.88 days; P=.01), and caplacizumab recipients were 1.55 times as likely to have a normalisation of the platelet count as those who received placebo.
The percentage of patients who had a recurrence of TTP at any time during the trial was 67 per cent lower with caplacizumab than placebo (12% vs 38%; P<.001 refractory disease developed in no patients the caplacizumab group and three placebo group.>
Commenting on the award, Dr Tom Blackburn, Chair of the British Pharmacological Society’s Industry Sub-Committee, said: “Caplacizumab represents a major innovation, not only in treating this life-threatening disorder, but also as the first-ever nanobody therapy.”