Takeda troops rare disease drug to regulators after glimpse at phase 3 data

Takeda has pressed go on plans to seek approval for its enzyme replacement therapy in an ultra-rare disease. Citing the “totality of the evidence” seen in phase 3, the Japanese drugmaker outlined its intent to head to regulators armed with data on the ADAMTS13 replacement therapy it acquired from Shire.

The phase 3 clinical trial enrolled people with congenital thrombotic thrombocytopenic purpura (cTTP). The condition is an ultra-rare subtype of a rare blood clotting disorder caused by ADAMTS13 deficiency. A lack of the protease can result in life-threatening acute episodes, leading Takeda to believe that providing a recombinant form of the enzyme will improve on the ADAMTS13-rich blood products used today.

Takeda now has pivotal data to support its belief. In an interim analysis of the randomized cross-over study, investigators linked TAK-755 to a 60% reduction in the incidence of thrombocytopenia events compared to the plasma-based therapies that are the current standard of care. The confidence interval for the reduction ranges from 30% to 70%.

ClinicalTrials.gov lists the number of acute thrombotic thrombocytopenic purpura events as the primary endpoint. Takeda’s statement lacks a p-value for the 60% reduction in thrombocytopenia events—or any other efficacy data—but the company said the totality of evidence from the analysis supports the efficacy and safety of TAK-755. The approach has been discussed with global regulatory agencies, Takeda said.

With the proportion of people having treatment-related adverse events coming in lower in the TAK-755 arm, 8.9%, than the active control group, 47.7%, Takeda is preparing to seek approval for what would be the first ADAMTS13 replacement therapy for the treatment of cTTP.

TAK-755 is one of the molecules that passed quickly through multiple hands as Baxter-spinout Baxalta was acquired by Shire, which was then itself bought by Takeda. In the hands of Takeda, the molecule has moved toward market in cTTP while advancing through earlier clinical tests in other indications including sickle cell disease.