Takeda (TSE: 4502/NYSE:TAK) today presented favorable interim results from a global pivotal Phase 3 randomized, controlled, open-label, crossover trial evaluating the safety and efficacy of TAK-755 (recombinant ADAMTS13) replacement therapy for the prophylactic treatment of congenital thrombotic thrombocytopenic purpura (cTTP), and pharmacokinetics (PK) characteristics of TAK-755, as well as long-term data on TAK-755 prophylaxis from a Phase 3b continuation study.
cTTP is an ultra-rare, chronic and debilitating blood clotting disorder caused by a deficiency in ADAMTS13 enzyme. Clinical presentation of cTTP lies on a spectrum of severity ranging from severe acute TTP events to chronic, recurring TTP manifestations (e.g., thrombocytopenia, hemolytic activity, headache, abdominal pain). Acute TTP events have a mortality rate of >90%, if left untreated.1 These studies were designed to evaluate the clinical benefit of TAK-755 in patients with cTTP across multiple clinically relevant endpoints and based on the totality of the evidence provided by efficacy, PK, safety and tolerability data. Both acute and subacute TTP events, including TTP-related organ-specific signs and symptoms were evaluated.
In the pivotal trial, no patient had an acute TTP event while receiving TAK-755 prophylactic treatment. TAK-755 also reduced the incidence of thrombocytopenia by 60%, as compared to plasma-based therapy (for the rate ratio = 0.40 TAK-755/plasma-based therapy with 95% Confidence Interval 0.3 to 0.7). Thrombocytopenia, an important marker of disease activity, was the most frequently observed TTP manifestation. In addition, the results show that TAK-755 demonstrated a favorable safety and tolerability profile, with a potential safety advantage over plasma-based therapies. In the pivotal trial, treatment-emergent adverse events (TEAEs) were reported in 10.3% of patients ages 12-68 receiving TAK-755 compared to 50% of patients receiving plasma-based therapy. (Presentation Number: OC 14.1)
“These findings suggest that recombinant ADAMTS13 is a promising innovative investigational treatment for patients with cTTP,” said Marie Scully, M.D., Department of Haematology, University College London Hospitals, London, United Kingdom. “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.”
PK characteristics of ADAMTS13 after a single infusion (0-168 hours) were evaluated and compared to plasma-based therapy in 36 cTTP patients aged 12 and older. Patients receiving TAK-755 achieved a five-fold increase in their ADAMTS13 activity levels compared to those receiving plasma-based therapy (Cmax 100% activity for TAK-755 vs. 19% activity for plasma-based therapy) and lower variability (23.8% vs. 56% coefficient of variation [CV], respectively). (Presentation Number: OC 14.2)
“People with cTTP face life-threatening events and debilitating symptoms, and have no approved treatment for the disease,” said Daniel Curran, M.D., Head, Rare Genetics & Hematology Therapeutic Area Unit at Takeda. “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.”
Takeda also presented an interim analysis of the Phase 3b continuation study, evaluating the safety and efficacy of long-term TAK-755 prophylaxis in 29 patients with cTTP (mean ± SD age: 40.4 ± 12.1; 62% female; median [range] duration of treatment 0.7 [0-1.4] years). Results demonstrated a consistently favorable safety profile with TAK-755 prophylaxis and no development of neutralizing antibodies. Zero acute TTP events occurred during TAK-755 prophylaxis, and the incidence rates of subacute TTP events and TTP manifestations were comparable to those with TAK-755 prophylaxis in the pivotal study. (Presentation Number: OC 14.4)
Results were presented today in three oral presentations delivered at the International Society on Thrombosis and Haemostasis (ISTH) 2023 Congress. The full text of Takeda abstracts at ISTH can be found here: https://www.isth2023.org/program.
TAK-755 is an investigational therapy that has not been approved by the U.S. Food & Drug Administration (FDA), European Medicines Agency (EMA) or other Regulatory authorities. The FDA has accepted and granted Priority Review for Takeda’s Biologics License Application (BLA) for TAK-755 for the treatment of cTTP.
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