Source – Takeda
On June 25, 2023, Takeda has shared promising interim findings from a global Phase III clinical trial of TAK-755 (recombinant ADAMTS13) for the prophylactic treatment of congenital thrombotic thrombocytopenic purpura (cTTP). The trial assessed the safety and efficacy of TAK-755 as well as its pharmacokinetics (PK) characteristics. Additionally, long-term data from a Phase IIIb continuation study on TAK-755 prophylaxis were presented.
cTTP is an extremely rare and chronic blood clotting disorder caused by a deficiency in the ADAMTS13 enzyme. The severity of cTTP varies, ranging from acute TTP events with high mortality rates if left untreated to recurring TTP symptoms such as thrombocytopenia, hemolytic activity, headache, and abdominal pain. The objective of these studies was to evaluate the clinical benefits of TAK-755 in patients with cTTP based on various endpoints, including efficacy, PK, safety, and tolerability data. Both acute and subacute TTP events and organ-specific signs and symptoms related to TTP were assessed.
The pivotal trial revealed that no patient experienced an acute TTP event while receiving TAK-755 prophylactic treatment. TAK-755 also demonstrated a 60% reduction in the incidence of thrombocytopenia compared to plasma-based therapy. Thrombocytopenia is a crucial indicator of disease activity and is the most frequently observed TTP manifestation. Furthermore, TAK-755 exhibited a favorable safety and tolerability profile, potentially surpassing plasma-based therapies in terms of safety. In the trial, treatment-emergent adverse events (TEAEs) were reported in 10.3% of patients aged 12-68 receiving TAK-755, while 50% of patients receiving plasma-based therapy reported TEAEs.
Dr. Marie Scully from the Department of Haematology at University College London Hospitals commented, “These findings suggest that recombinant ADAMTS13 is a promising innovative investigational treatment for patients with cTTP. Given the high burden of illness these patients experience, complicated by unpredictable acute episodes and multiple disease-related complications, this is a much-needed option, supported through a first-of-its-kind clinical trial.”
The PK characteristics of ADAMTS13 were evaluated after a single infusion (0-168 hours) and compared to plasma-based therapy in 36 cTTP patients aged 12 and older. Patients receiving TAK-755 demonstrated a five-fold increase in ADAMTS13 activity levels compared to those receiving plasma-based therapy. Additionally, TAK-755 exhibited lower variability in activity levels compared to plasma-based therapy.
“People with cTTP face life-threatening events and debilitating symptoms and have no approved treatment for the disease. We are encouraged by what these positive results mean for people living with this rare disorder, and we look forward to continuing to advance this program for patients who may benefit from treatment with TAK-755.”
– Dr. Daniel Curran, Head of Rare Genetics & Hematology Therapeutic Area Unit at Takeda
Takeda also shared an interim analysis of a Phase 3b continuation study, which assessed the long-term safety and efficacy of TAK-755 prophylaxis in 29 patients with cTTP. These patients had a mean age of 40.4 ± 12.1 years, with 62% being female. The median duration of treatment was 0.7 years. The results revealed a consistently positive safety profile for TAK-755 prophylaxis, with no development of neutralizing antibodies. Notably, there were no acute TTP events reported during TAK-755 prophylaxis, and the incidence rates of subacute TTP events and TTP manifestations were comparable to those observed in the pivotal study. This information was presented as part of the ISTH 2023 Congress (Presentation Number: OC 14.4). It is important to note that TAK-755 is still under investigation and has not received approval from regulatory authorities such as the FDA or EMA. However, the FDA has accepted and granted Priority Review for Takeda’s Biologics License Application (BLA) for TAK-755 as a treatment for cTTP.
