Reports for VERTIS Mono and VERTIS Factorial studies of ertugliflozin and ertugliflozin + sitagliptin to treat type 2 diabetes-Merck Inc +Pfizer

Merck in partnership with Pfizer Inc. announced that two Phase III studies (VERTIS Mono and VERTIS Factorial) of ertugliflozin, an investigational oral SGLT-2 inhibitor for the treatment of patients with type 2 diabetes, met their primary endpoints. The study results showed statistically significant reductions in A1C (a measure of average blood glucose) for both ertugliflozin doses tested (5 mg and 15 mg daily). These results from the VERTIS clinical development program of ertugliflozin will be presented for the first time at the 76th Scientific Sessions of the American Diabetes Association.

A 26-week investigational study (VERTIS Mono) which evaluated ertugliflozin as monotherapy met its primary endpoint showing that patients randomized to ertugliflozin 5 mg and 15 mg had significantly greater A1C reductions of 0.99 percent and 1.16 percent, respectively, compared with placebo. In addition, significantly more patients taking ertugliflozin 5 mg and 15 mg achieved the A1C treatment goal of less than 7.0 percent (28.2 percent and 35.8 percent, respectively) compared with placebo (13.1 percent), which was a secondary endpoint of the study.

Overall adverse event (AE) rates were similar between ertugliflozin 5 mg (52.6 percent), ertugliflozin 15 mg (55.9 percent) and placebo (52.3 percent), with a similar rate of one or more serious AEs across all groups (4.5 percent for ertugliflozin 5 mg; 1.3 percent for ertugliflozin 15 mg; 1.3 percent for placebo). The rates of discontinuations due to AEs were low across all groups (2.6 percent for ertugliflozin 5 mg; 2.0 percent for ertugliflozin 15 mg; 3.3 percent for placebo). A higher incidence of genital mycotic infections in females was observed in patients taking ertugliflozin 15 mg (22.6 percent) and ertugliflozin 5 mg (16.4 percent) compared with placebo (5.6 percent). There was no increase in the incidence of urinary tract infections with either dose of ertugliflozin relative to placebo.

VERTIS Factorial, a 26-week investigational study, evaluated the co-administration of ertugliflozin and Merck�s DPP-4 inhibitor Januvia (sitagliptin). This study also met its primary endpoint, with greater reductions in A1C observed in patients taking ertugliflozin in combination with sitagliptin compared to ertugliflozin or sitagliptin alone. An A1C reduction of 1.5 percent was observed in both combinations studied (ertugliflozin 5 mg or 15 mg with sitagliptin 100 mg), as compared with A1C reductions of 1.0 percent with ertugliflozin 5 mg alone, 1.1 percent with ertugliflozin 15 mg alone, and 1.1 percent with sitagliptin 100 mg alone. In addition, the co-administration of ertugliflozin and sitagliptin was significantly more effective than ertugliflozin or sitagliptin alone in achieving the A1C treatment goal of less than 7.0 percent, which was a secondary endpoint of the study. Specifically, 52.3 percent of patients taking ertugliflozin 5 mg in combination with sitagliptin 100 mg and 49.2 percent of patients taking ertugliflozin 15 mg in combination with sitagliptin 100 mg reached an A1C goal of less than 7.0 percent. In comparison, 26.4 percent achieved this A1C goal with ertugliflozin 5 mg, 31.9 percent with ertugliflozin 15 mg, and 32.8 percent with sitagliptin 100 mg.

VERTIS CV, a randomized, double-blind, placebo-controlled, parallel-group trial, was recently expanded to enable testing for superiority in improving CV outcomes in type 2 diabetes patients. The study is now targeting enrollment of approximately 8,000 patients with type 2 diabetes and established vascular disease. Pre-specified secondary endpoints were added to test for superiority on the composite of CV death and hospitalization for heart failure and superiority on CV death alone. The primary endpoint of the trial continues to be to assess the non-inferiority of ertugliflozin versus placebo on the composite of CV death, nonfatal myocardial infarction or nonfatal stroke (MACE).

Comment: Merck and Pfizer plan to submit ertugliflozin for FDA approval by the end of 2016, along with two combinations., one that combines ertugliflozin with the standard diabetes therapy metformin, another of ertugliflozin with Januvia.