The therapeutic effect of ADAMTS13 recombinant protease (trade name: Apadase α, English: Adzynma)

On November 9, 2023, Takeda Pharmaceutical announced that the U.S. Food and Drug Administration (FDA) has approved Adzynma (ADAMTS13, recombinant-krhn) for the preventive and on-demand treatment of adults and children with congenital thrombotic thrombocytopenic purpura (cTTP). Adzynma is the first and only FDA-approved recombinant ADAMTS13 (rADAMTS13) protein designed to address the unmet medical needs of cTTP patients by replacing the defective ADAMTS13 enzyme.

cTTP is an extremely rare chronic coagulation disorder mainly caused by ADAMTS13 enzyme deficiency. The disease is associated with acute events as well as debilitating chronic symptoms, including thrombocytopenia, microangiopathic hemolytic anemia, headache, and abdominal pain. If left untreated, the mortality rate from acute TTP events exceeds 90%. Therefore, it is particularly important to find effective treatments.

Adzynma provides patients with a treatment option to replace their defective ADAMTS13 enzyme, with reduced dosing time and dosage compared to traditional plasma-based treatments, and has shown good efficacy and safety. This approval marks a major advance in the treatment of cTTP and brings new hope to patients with this rare disease.

The FDA's approval of Adzynma was strongly supported by the first randomized, controlled, open-label, crossover Phase 3 clinical trial of cTTP. Efficacy, pharmacokinetics, safety and tolerability data, as well as data from continuation trials, were analyzed in the study. In the Phase 3 trial, patients received 40 IU/kg of Adzynma weekly as an intravenous or plasma-based treatment. The trial is divided into three phases according to time period: 1-6 months (Phase 1) is the regimen at registration, 7-12 months (Phase 2) is alternative treatment, and all patients receive Adzynma in 13-18 months (Phase 3).

Among the 37 patients who received Adzynma prophylaxis, there were no acute TTP events; among the 38 patients who received plasma-based therapy, one acute TTP event occurred. In the controlled Phase 1 and 2 studies, no subacute TTP events were reported in patients treated with Adzynma, whereas in patients receiving plasma-based therapy, five subacute TTP events occurred in four patients. During the continuation phase (Phase 3), only two patients receiving Adzynma prophylaxis experienced two subacute TTP events.

Additionally, the mean annualized event rate for manifestations of thrombocytopenia was 2.0 (SD=4.706) in patients receivingAdzynma compared with 4.44 (SD=6.312) in patients receiving plasma-based therapy. Although the clinical significance of this comparison is unclear, thrombocytopenia, a manifestation of TTP, remains an important biomarker of disease activity.

Adzynma is a recombinant form of ADAMTS13 protein. In pharmacokinetic assessments, patients receiving 40 IU/kg Adzynma intravenously experienced a 4- to 5-fold increase in ADAMTS13 activity after a single infusion compared with plasma-based therapy. This indicates that Adzynma has a significant effect in increasing ADAMTS13 activity in the blood.

In terms of safety,Adzynma shows good safety characteristics. The most common adverse reactions (incidence more than 5%) include headache, diarrhea, migraine, abdominal pain, nausea, upper respiratory tract infection, dizziness and vomiting. Notably, patients treated with Adzynma did not develop neutralizing antibodies, further supporting its safety and tolerability.

To sum up,The approval of Adzynma provides a new treatment option for cTTP patients and heralds a major breakthrough in the field of rare disease treatment. This progress not only brings hope to patients, but also provides new ideas and directions for the treatment of similar diseases in the future.

Reference link:https://www.drugs.com/newdrugs/fda-approves-adzynma-adamts13-recombinant-krhn-enzyme-replacement-therapy-congenital-thrombotic-6141.html