Merck & Co. acknowledged today that its supplemental NDA seeking to append cardiovascular data to the prescribing labels of diabetes treatments Januvia® (sitagliptin), Janumet® (sitagliptin and metformin HCl), and Janumet XR® (sitagliptin and metformin HCl extended-release) has been rejected by the FDA.
The company said it received a Complete Response Letter (CRL) from the FDA in response to its supplemental application, in which it sought to include data from the Phase III TECOS (Trial Evaluating Cardiovascular Outcomes with Sitagliptin) study in the prescribing information of the sitagliptin-containing medicines.
Merck did not disclose the concerns raised by the FDA in the CRL.
“Merck is reviewing the letter and will discuss next steps with the FDA,” the company stated.
In results from TECOS announced in April 2015, Merck said the 14,724-patient study showed Januvia to have achieved its primary endpoint of noninferiority for the composite cardiovascular endpoint. Secondary endpoints showed there was no increase in hospitalization for heart failure in the sitagliptin group versus placebo, the company added.
TECOS was led by an independent academic research collaboration between the University of Oxford Diabetes Trials Unit and the Duke University Clinical Research Institute.
In January, researchers from those institutions, Merck, and other participants published results from the study in the journal Diabetes Care, published by the American Diabetes Association. The researchers concluded that among older patients with well-controlled type 2 diabetes and cardiovascular disease, sitagliptin had neutral effects on cardiovascular risk and raised no significant safety concerns.
Januvia is a dipeptidyl peptidase 4 (DPP-4) inhibitor indicated for adults with type 2 diabetes as an adjunct to diet and exercise. Januvia won its first FDA approval in 2006.
Januvia and Janumet both achieved blockbuster-level product sales last year. Januvia finished 2016 generating $3.908 billion, up 1% from $3.863 billion a year earlier. Janumet racked up $2.201 billion last year, a 2% increase from $2.151 billion in 2015. Merck attributed the increase to sales growth in the U.S. that was partially offset by lower sales in Japan due to the timing of shipments.