RARE Daily

FDA Grants Priority Review of Takeda’s Treatment of Congenital Thrombotic Thrombocytopenic Purpura

May 17, 2023

Rare Daily Staff

The U.S. Food and Drug Administration has accepted Takeda’s Biologics License Application for TAK-755, an enzyme replacement therapy for the treatment of congenital thrombotic thrombocytopenic purpura, an ADAMTS13 deficiency disorder.

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

There are no medications specifically approved by regulatory authorities for routine prophylactic treatment of cTTP. Current treatment centers around plasma therapy, either by infusion or plasma exchange. Plasma therapy is time consuming and can be associated with severe treatment complications that can include treatment-limiting volume overload and allergic reactions.

The TAK-755 application was accepted by the FDA on May 16, and has been granted Priority Review. FDA has also granted TAK-755 Rare Pediatric Disease designation for cTTP. TAK-755 has previously received Fast Track and Orphan Drug designations in cTTP.

If approved, TAK-755 would be the first and only recombinant ADAMTS13 (rADAMTS13) replacement therapy for cTTP, a disorder with considerable unmet patient need.

“There is a critical need for treatment options for people living with cTTP, an ultra-rare, life-threatening disorder that has no therapies specifically approved for prophylactic treatment,” said Daniel Curran, head, Rare Genetics & Hematology Therapeutic Area Unit at Takeda. “TAK-755 is the first and only treatment in clinical development that provides targeted replacement of ADAMTS13, addressing the underlying cause of the disease. We continue to be encouraged by the data and are working closely with the FDA and other global regulatory bodies with the goal to bring this treatment to patients.”

The application is supported by the totality of the evidence provided by efficacy, pharmacokinetic, safety and tolerability data from the first randomized, controlled trial in cTTP, and supported by long-term safety and efficacy data from a continuation study. The phase 3 trial was designed to evaluate the clinical benefit of TAK-755 across multiple clinically relevant endpoints, compared to plasma-based therapies, in a randomized cross-over study.

The interim results, announced by Takeda in January 2023, showed that TAK-755 reduced the incidence of thrombocytopenia events by 60 percent, an important marker of disease activity in cTTP, as compared to plasma-based therapy. 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 plasma-based therapies (47.7 percent). The interim analysis of the phase 3 results will be presented at an upcoming scientific meeting.

Takeda is also investigating the safety, efficacy, and pharmacokinetics of TAK-755 treatment in immune-mediated TTP (iTTP) in an ongoing phase 2b study.

Photo: Daniel Curran, head, Rare Genetics & Hematology Therapeutic Area Unit at Takeda


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