Investigational SGLT-2 Inhibitor Meets Primary Endpoint in Phase 3 Studies

Merck, in partnership with Pfizer Inc., has announced that VERTIS MET and VERTIS SITA met their primary endpoints. Both trials are Phase 3 studies of an investigational oral sodium-glucose co-transporter (SGLT-2) inhibitor, ertugliflozin, that is currently in development to help improve glycemic control in adult patients with type 2 diabetes (T2D).

Researchers will report that the tested doses, 5 mg daily and 15 mg daily, achieved statistically significant reductions in hemoglobin A1C when added to metformin or in initial co-administration with sitagliptin.

The results of these studies, along with 52-week extension data from 3 other studies in the VERTIS clinical development program of ertugliflozin, are being presented this weekend at the American Diabetes Association (ADA)’s 77^th Scientific Sessions in San Diego.

“We are pleased to share these new Phase 3 data with the scientific community that support the product profile of ertugliflozin as add-on therapy to metformin or for first-line use when combined with sitagliptin,” Sam Engel, MD, associate vice president of clinical research, cardiometabolic, and women’s health at Merck, said in a joint news release from Merck and Pfizer. “These studies are important milestones on our journey to bring this medicine to adults with type 2 diabetes and the physicians who care for them.”

“These results, combined with findings from other studies in the VERTIS program, underscore the potential of ertugliflozin as an important therapeutic option for adults with type 2 diabetes to help improve their glycemic control,” added James Rusnak, MD, PhD, chief development officer, cardiovascular and metabolic diseases, for Pfizer Global Product Development. “As the global burden of diabetes continues to rise, we are committed to meeting patients’ needs with additional treatment options to help manage their condition.”

VERTIS MET, a 26-week study, evaluated the efficacy and safety of ertugliflozin taken in combination with metformin. It was compared with placebo and metformin in adult patients with uncontrolled T2D who are taking metformin monotherapy.

VERTIS SITA, which is also a 26-week study, compared the efficacy and safety of initial combination therapy of ertugliflozin and Merck’s dipeptidyl peptidase (DPP)-4 inhibitor, Januvia (sitagliptin), with placebo.

The VERTIS clinical development program is comprised of 9 Phase 3 trials including approximately 12,600 adult patients with T2D. An ongoing cardiovascular (CV) outcomes trial of ertugliflozin, VERTIS CV, recently completed enrollment with approximately 8000 patients with T2D and established vascular disease. The primary endpoint of that trial is to assess the noninferiority of ertugliflozin to placebo on the composite of CV death, nonfatal myocardial infarction, or nonfatal stroke. VERTIS CV was expanded in 2016 with prespecified secondary endpoints added to test for superiority on the composite of CV death and hospitalization for heart failure, as well as for superiority on CV death alone.

Marketing applications for ertugliflozin and for 2 fixed-dose combination products (ertugliflozin/Januvia; ertugliflozin/metformin) are under review with the US Food and Drug Administration (FDA) and the European Medicines Agency. According to the partner companies, the Prescription Drug User Fee Act action date from the FDA is in December 2017 for the 3 New Drug Applications.