Merck, known as MSD outside the United States and Canada, in partnership with Pfizer Inc. announced that a phase 3 study (VERTIS SITA2) of ertugliflozin, an investigational oral SGLT2 inhibitor for the treatment of patients with type 2 diabetes, met its primary endpoint. Both 5 mg and 15 mg daily doses of ertugliflozin showed significantly greater reductions in A1C of 0.69 per cent and 0.76 per cent, respectively, compared with placebo (p<0.001, for both comparisons), when added to patients on a background of sitagliptin (100 mg/day) and stable metformin (=1500 mg/day). These study results were presented for the first time during an oral session today at the 52nd Annual Meeting of the European Association for the Study of Diabetes (EASD) in Munich, Germany.
Merck and Pfizer plan to submit New Drug Applications to the US Food and Drug Administration for ertugliflozin and two fixed-dose combinations (ertugliflozin plus Januvia (sitagliptin) and ertugliflozin plus metformin) by the end of 2016, with additional regulatory submissions outside of the US to follow in 2017.
“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, M.D., vice president, late stage development, diabetes and endocrinology, Merck.
In this double-blind, randomized, placebo-controlled study, 463 patients with type 2 diabetes and a baseline A1C of 7.0 – 10.5 percent were randomized to receive ertugliflozin 5 mg, ertugliflozin 15 mg, or placebo in a 1:1:1 ratio. In addition to meeting the primary endpoint of reducing A1C at 26 weeks, ertugliflozin also met the following key secondary endpoints in the study:
A greater proportion of patients taking ertugliflozin 5 mg and 15 mg achieved the A1C treatment goal of less than 7.0 percent (32.1 percent and 39.9 percent, respectively) compared with the placebo group (17.0 percent) (p<0.001, for both comparisons based on adjusted odds ratios);
Placebo-adjusted mean reduction in body weight of 4.4 lbs (2.0 kg) for the 5 mg dose and 3.7 lbs (1.7 kg) for the 15 mg dose (p<0.001, for both comparisons);
Placebo-adjusted mean reductions in fasting plasma glucose (FPG) 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 (p<0.001, for both comparisons);
Placebo-adjusted mean reductions in systolic blood pressure of 2.9 mmHg (5 mg, p=0.019) and 3.9 mmHg (15 mg, p=0.002).
“We are pleased to share these new data on investigational ertugliflozin with the scientific community, following the first presentations of phase 3 data for ertugliflozin at the American Diabetes Association’s 76th Scientific Sessions in June,” said James Rusnak, M.D., Ph.D., chief development officer, cardiovascular & metabolics, Pfizer. “Type 2 diabetes is a progressive disease and these study results help support the clinical profile of ertugliflozin as an add-on therapy for patients who may require multiple treatment combinations to help reach their blood sugar goals.”
Overall adverse event (AE) rates were generally similar between ertugliflozin 5 mg (41.7 percent), ertugliflozin 15 mg (43.8 percent) and placebo (48.4 percent), with a similar rate of one or more serious AEs across all groups (4.5 percent for ertugliflozin 5 mg; 2.0 percent for ertugliflozin 15 mg; 3.3 percent for placebo). The rates of discontinuations due to AEs were low across all groups (3.2 percent for ertugliflozin 5 mg; 0.7 percent for ertugliflozin 15 mg; 0.7 percent for placebo). In the study, a higher incidence of genital mycotic infections was observed in patients taking ertugliflozin 5 mg and ertugliflozin 15 mg (males: 4.9 percent and 3.7 percent, respectively, vs. no events for placebo; females: 8.0 percent and 12.7 percent, respectively, vs. 1.9 percent for placebo). Urinary tract infection rates were low across the ertugliflozin 5 mg, ertugliflozin 15 mg and placebo groups (2.6 percent, 4.6 percent and 2.0 percent, respectively). Across groups, there were similar rates for symptomatic hypoglycemia (3.8 percent for ertugliflozin 5 mg; 0.7 percent for ertugliflozin 15 mg; 2.6 percent for placebo) and for hypovolemia adverse events (0.6 percent for ertugliflozin 5 mg; no events for ertugliflozin 15 mg; 0.7 percent for placebo).
In addition to the VERTIS MONO and VERTIS FACTORIAL studies, which were presented at the 76th Scientific Sessions of the American Diabetes Association, VERTIS SITA2 is a part of the VERTIS clinical development program comprised of a total of nine phase 3 trials in approximately 12,600 adults with type 2 diabetes. Results from the other six VERTIS trials will be submitted for publication and/or presentation at future scientific congresses.
Januvia is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Januvia should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis. Januvia has not been studied in patients with a history of pancreatitis. It is unknown whether patients with a history of pancreatitis are at increased risk of developing pancreatitis while taking Januvia.