Takeda’s TAK-755 shows potential in Phase 3 trial for cTTP prophylaxis

Takeda Pharmaceutical Company has revealed promising interim results from its global Phase 3 trial of TAK-755, a recombinant ADAMTS13 protein in development for the prophylactic treatment of congenital thrombotic thrombocytopenic purpura (cTTP).

This makes TAK-755 the only recombinant ADAMTS13 protein under development, targeting an unmet medical need in TTP patients by replacing the missing or deficient ADAMTS13 enzyme.

cTTP is an ultra-rare, chronic, and debilitating blood clotting disorder resulting from an ADAMTS13 enzyme deficiency. Clinical manifestations of cTTP span a severity spectrum, from severe acute TTP events to chronic, recurring TTP manifestations such as thrombocytopenia, hemolytic activity, headache, and abdominal pain. Acute TTP events exhibit a mortality rate exceeding 90% if left untreated.

In the pivotal trial, no patient experienced an acute TTP event while on TAK-755 prophylaxis. TAK-755 also reduced thrombocytopenia incidence by 60% compared to plasma-based therapy. Additionally, TAK-755 demonstrated a favorable safety and tolerability profile, with treatment-emergent adverse events (TEAEs) reported in 10.3% of patients aged 12-68 receiving TAK-755, compared to 50% of patients on plasma-based therapy.

Pharmacokinetics (PK) characteristics of ADAMTS13 after a single infusion were evaluated, revealing patients receiving TAK-755 achieved a five-fold increase in their ADAMTS13 activity levels compared to those on plasma-based therapy, and exhibited lower variability.

An interim analysis of the Phase 3b continuation study evaluating TAK-755’s long-term prophylaxis in 29 cTTP patients also showed a consistently favorable safety profile. No development of neutralizing antibodies was reported, and no acute TTP events occurred during TAK-755 prophylaxis.

Daniel Curran — Takeda Head of Rare Genetics & Hematology Therapeutic Area Unit said: “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.”

TAK-755 is an investigational therapy yet to be approved by the U.S. Food & Drug Administration (FDA), European Medicines Agency (EMA), or other regulatory authorities. However, the FDA has accepted Takeda’s Biologics License Application (BLA) for TAK-755 for the treatment of cTTP and granted it Priority Review.