Takeda Reports Favorable Phase 3 Safety and Efficacy Results of Enzyme Replacement Therapy in cTTP

Takeda reported that the totality of evidence from a pre-planned interim analysis of a pivotal phase 3 study supports the efficacy and safety of TAK-755 as enzyme replacement therapy for congenital thrombotic thrombocytopenic purpura.

The trial was designed to evaluate the clinical benefit of TAK-755 across multiple clinically relevant endpoints and based on the totality of the evidence provided by efficacy, pharmacokinetic, safety and tolerability data. This approach was discussed with global regulatory agencies. The study evaluated TAK-755 compared to plasma-based therapies, which are the current standard of care (SoC), in a randomized cross-over study. The interim results showed that TAK-755 reduced the incidence of thrombocytopenia events by 60 percent, an important marker of disease activity in cTTP, as compared to SoC. The proportion of subjects experiencing adverse events determined to be related to the treatment was substantially lower among subjects during treatment with TAK-755 (8.9 percent) compared to that while receiving SoC therapy (47.7 percent).

Based on these data from the phase 3 interim analysis, Takeda aims to seek marketing authorization for TAK-755 as the first recombinant ADAMTS13 replacement therapy for cTTP, a disorder with considerable unmet patient need.

“The results of the trial are very encouraging, and we look forward to continuing to engage with global regulatory bodies with the aim of bringing TAK-755 to patients as rapidly as possible,” said Daniel Curran, head, Rare Genetics and Hematology Therapeutic Area Unit at Takeda.

Takeda plans to submit the results of this interim analysis for presentation at an upcoming scientific meeting.

Congenital thrombotic thrombocytopenic purpura (cTTP) is an ultra-rare sub-type of thrombotic thrombocytopenic purpura (TTP), a rare, chronic and debilitating blood clotting disorder caused by a deficiency in ADAMTS13 protease. Acute TTP has a mortality rate of greater than 90 percent, if left untreated.

cTTP is an ultra-rare, chronic, and debilitating blood clotting disorder associated with life-threatening acute episodes and debilitating chronic symptoms. cTTP is a sub-type of TTP that has an estimated prevalence of no more than 5 percent of patients with TTP. It develops due to deficiency in ADAMTS13, a von Willebrand factor (VWF) cleaving protease, which results in the accumulation of ultra-large VWF multimers in the blood. The accumulation of ultra-large VWF multimers leads to uncontrolled platelet aggregation and adhesion. This can lead to abnormal clotting in the small blood vessels of the body and is associated with hemolytic anemia and low platelet levels (thrombocytopenia).

cTTP has both acute and chronic manifestations (including stroke and cardiovascular disease) and is associated with a significant disease burden. Patients’ quality of life and lifespan are significantly reduced compared to the general population, due to serious, ongoing widespread organ damage and other co-morbidities resulting from an ADAMTS13-deficient state. The current standard of care for cTTP is plasma therapy,16 which is insufficient in restoring ADAMTS13, time-consuming, and costly.

TAK-755 is the first and only recombinant ADAMTS13 protein in development. It provides targeted therapy to address an unmet medical need in patients with thrombotic thrombocytopenic purpura (TTP), by replacing the missing or deficient ADAMTS13 enzyme.

TAK-755 is also being investigated in a phase 2 study to evaluate the pharmacokinetics, safety and efficacy of rADAMTS13 in immune-mediated TTP (iTTP).

TAK-755 was granted Orphan Drug designation by the U.S. Food and Drug Administration for the treatment and prevention of TTP including its congenital, acquired idiopathic, and secondary forms; and by the European Medicines Agency and Japan’s Ministry of Health, Labour and Welfare for the treatment of TTP. The FDA has also granted TAK-755 Fast Track designation for the treatment, prevention, and routine prophylaxis of acute episodes of TTP in patients with hereditary (congenital) ADAMTS13 deficiency.

Author: Rare Daily Staff