Recombinant ADAMTS13 Approved in the UK for Congenital Thrombotic Thrombocytopenic Purpura

The Medicines and Healthcare products Regulatory Agency (MHRA) in the UK has approved recombinant ADAMTS13 (rADAMTS13; ADZYNMA) for the treatment of congenital thrombotic thrombocytopenic purpura (CTTP).¹

Developed by Takeda, rADAMTS13 was approved in the US in November 2023, in Japan in March 2024, and in the European Union in August 2024.^2-4

A phase 3, open-label, crossover trial published in the New England Journal of Medicine assessed the safety and pharmacokinetics of the recombinant protein. Forty-eight patients with CTTP were randomly assigned 1:1 to two six-month periods of prophylaxis with intravenous rADAMTS13 (40 IU per kilogram of body weight) or standard therapy. For another six months, all patients received rADAMTS13. The primary outcome was acute TTP events.⁵

Patients who received rADAMTS13 did not experience acute TTP events during prophylaxis, compared with one patient receiving standard therapy. The most frequent TTP manifestation was thrombocytopenia, with an annualized event rate of 0.74 with rADAMTS13 and 1.73 with standard therapy.⁵

Adverse events (AEs) occurred in 71% of patients who received rADAMTS13 and in 84% of patients who received standard therapy, with 9% and 48% being treatment-related, respectively. No patients in the rADAMTS13 group discontinued treatment due to AEs, compared with 8 patients in the standard therapy group.⁵

“During prophylaxis with recombinant ADAMTS13 in patients with congenital TTP, ADAMTS13 activity reached approximately 100% of normal levels, adverse events were generally mild or moderate in severity, and TTP events and manifestations were rare,” the study authors wrote.⁵