Takeda hoping for third time lucky as it resubmits alogliptin and combo in US
This article was originally published in Scrip
Takeda has re-filed new drug applications in the US for its antidiabetic alogliptin and a fixed-dose combination of the dipeptidyl peptidase IV inhibitor with pioglitazone (Takeda's Actos), hoping that this time it will be able to satisfy the agency's concerns after years of delays.
"Takeda anticipates that these applications will be reviewed within the next six months," it said, stressing that the products remain a top priority for the company. Given the difficulty in gaining their approval and rising competition in the DPP-4 sector in the US, there had been some speculation that the firm might decide to give up on alogliptin in this market.
But while the resubmissions show that the Japanese company remains committed to gaining regulatory clearances, if granted these now look set to be well after the looming first loss of exclusivity for Actos next month. Generic versions of combinations of the thiazolidinedione drug - which in various forms is currently Takeda's top-selling product - are also expected to enter the US market in December.
The firm has not disclosed exactly what data have been requested by the FDA for alogliptin, which received second complete response letters for monotherapy use and the fixed-dose combination with Actos this April. However, it said that updated additional postmarketing data from outside the US (from Japan) and "significant new data" from three Phase III studies in its ongoing global clinical trial programme had been included in the resubmissions.
Takeda has confirmed to Scrip that no additional studies were requested by the FDA in the complete response letters and that the agency did not raise any cardiovascular safety concerns.
The ongoing EXAMINE programme with alogliptin in diabetes patients with acute coronary syndrome is being conducted to satisfy the FDA's cardiovascular risk assessment guidelines for new type 2 diabetes agents. The firm views the interim results from this as meeting the agency's criteria, although the final results from the trial are not expected until 2015.
Takeda and its investors will be hoping the resubmissions are the last hurdle alogliptin has to overcome before reaching the US market, following one delay after another. The April complete response letters were themselves put back after the FDA requested more time for its review last November.
They followed first complete response letters in 2009 that requested additional cardiovascular safety studies, after original filings made back in December 2007 for the monotherapy and September 2008 for the combination, as an adjunct to diet and exercise for type 2 diabetes.
If approved this time around, the combination stands to become the first one-pill formulation of a DPP-4 inhibitor and a thiazolidinedione antidiabetic in the US; a fixed-dose combination with metformin was also filed in this market last November.
Japan is so far the only major country to approve any alogliptin product, granting approval to the monotherapy in April 2010 (as Nesina) and a single-pill combination with pioglitazone around a year ago (as Liovel). European marketing authorisation applications for alogliptin alone and fixed-dose combinations with either pioglitazone or metformin have been accepted for review over the past few months.