Pfizer and Merck plan to file new drug applications with FDA for the SGLT2 inhibitor by the end of the year. One combination would pair ertugliflozin with Januvia, the blockbuster DPP-4 inhibitor.
Merck and Pfizer today announced that ertugliflozin, a sodium glucose co-transporter-2 (SGLT2) inhibitor they are developing together, brought significantly greater reductions in glycated hemoglobin (A1C) compared with placebo. The drug was studied in patients with type 2 diabetes (T2D) in combination with sitagliptin and metformin.
Results from the phase 3 VERTIS SITA2 trial were presented today at the 52nd annual meeting of the European Association for the Study of Diabetes in Munich, Germany.
According to a statement, the companies plan to file new drug applications with FDA by the end of the year for ertugliflozin and for 2 fixed dose combinations: 1 combining the SGLT2 inhibitor with metformin, and the other with its sitagliptin, the Merck blockbuster dipeptidyl peptidase-4 (DPP-4) inhibitor sold as Januvia.
“It is encouraging to see further data from the VERTIS clinical development program in support of combining ertugliflozin, an SGLT2 inhibitor, with the DPP-4 inhibitor sitagliptin, which was first approved 10 years ago,” said Peter Stein, MD, vice president for late stage development, diabetes and endocrinology at Merck.
The double-blind, randomized trial involved 463 patients with T2D, who had a baseline A1C between 7% and 10.5%. Patients were randomized to receive 5 mg of ertugliflozin, 15 mg of ertugliflozin, or placebo in a 1:1:1 ratio. All 3 groups were on background therapy of 100 mg per day of sitagliptin and stable metformin of at least 1500 mg per day. Findings reported were:
As a class, SGLT2 inhibitors are not approved for weight loss or to reduce hypertension, but multiple studies have shown that the mechanism of action, which causes excess glucose to be expelled through the urinary tract, has a positive effect on both. Because the unique mechanism operates separately from that of other T2D therapies, SGLT2 have been studied for use in combination with other classes, including insulin, DPP-4 inhibitors and glucagon-like peptide-1 receptor agonists. Glyxambi, which combines the SGLT2 inhibitor empagliflozin and the DPP-4 inhibitor linagliptin, is already approved by FDA, and Qtern, a combination of dapagliflozin and saxagliptin, was recently approved in Europe.
The roster of combinations for T2D also include those with SGLT2 inhibitors and metformin. In May, FDA approved Invokamet, which combines metformin with canagliflozin, for use as a first-line therapy after previously approving it for patients who were already being treated for T2D.