Merck, Pfizer Announce Positive Results for Ertugliflozin

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:

• The study drug met its primary endpoint, with patients on the 5 mg dose of the study drug achieving a 0.69% mean A1C reduction, and those on the 15 mg dose achieving a 0.76% mean A1C reduction.
• A higher share of patients taking ertugliflozin achieved an A1C of 7% or less (32.1% for the 5 mg dose; 39.9% for the 15 mg dose), compared with only 17% for the placebo group.
• Placebo-adjusted mean reductions in body weight of 4.4 pounds (2.0 kg) for the 5 mg dose and 3.7 pounds (1.7 kg) for the 15 mg dose.
• Placebo-adjusted mean reductions in fasting plasma glucose of 25.1 mg/dL (1.4 mmol/L) for the 5 mg dose and 31.3 mg/dL (1.7 mmol/L) for the 15 mg dose.
• For blood pressure, placebo-adjusted mean reductions is systolic blood pressure of 2.9 mmHg for the 5 mg dose and 3.9 mmHg for the 15 mg dose.

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.