Takeda Pharmaceutical Co has resubmitted two New Drug Applications to regulators in the USA for its investigational type 2 diabetes therapy alogliptin and the fixed-dose combination of the drug and the Japanese drugmaker's Actos (pioglitazone).
The refiling with the US Food and Drug Administration comes after Takeda undertook a cardiovascular outcomes trial, titled EXAMINE, for alogliptin, a selective dipeptidyl peptidase IV inhibitor (DPP-4) inhibitor. The NDA for alogliptin was originally submitted in December 2007, a year before the FDA issued fresh guidelines for diabetes drugs but nevertheless the agency issued a complete response letter to Takeda, saying it did not believe the amount of existing data was "sufficient to meet certain statistical requirements outlined in that new guidance”.
The resubmissions contain interim results from EXAMINE and David Recker, head of clinical science at Takeda Global R&D Center, said the firm believes the data "satisfy the FDA's cardiovascular safety requirements to allow the agency to complete its review of our NDA, and further support the product profile of alogliptin". He noted that if approved, alogliptin/pioglitazone will be the first type 2 diabetes treatment option in the USA to include both a DPP-4 inhibitor and a thiazolidinedione (TZD) in a single tablet. Final study results are expected in 2014.
Twelve Phase III trials of alogliptin involving more than 8,000 patients have been conducted in over 1,000 centres worldwide. It was studied as a once-daily monotherapy and as an add-on to several other classes of antidiabetics, including metformin, TZDs, insulin and sulfonylureas. In these studies, alogliptin 25mg, taken once daily, demonstrated statistically significant reductions in haemoglobin A1c. Of the 8,000 patients, the alogliptin/pioglitazone studies included more than 3,000 patients.
NDAs for alogliptin and the combo were approved in April 2010 and July 2011 respectively by the Japanese Ministry of Health, Labour and Welfare.