OREANDA-NEWS. Takeda Pharmaceuticals International GmbH (Takeda), a leading contributor to innovative Type 2 diabetes treatments, presented alogliptin and fasiglifam data at the 49th Annual Meeting of the European Association for the Study of Diabetes (EASD) in Barcelona, Spain. Data from the global EXAMINE (EXamination of CArdiovascular OutcoMes: AlogliptIN vs. Standard of CarE in Patients with Type 2 Diabetes Mellitus and Acute Coronary Syndrome) CV safety outcomes trial indicated that alogliptin did not increase CV ischemic events including all-cause mortality (death from any cause), nonfatal myocardial infarction, nonfatal stroke, and urgent revascularization due to unstable angina. Additionally, EXAMINE exploratory data presented showed rates of hospitalization for heart failure were comparable across alogliptin and placebo groups.[2]

The company also presented Phase 3 data on the investigational compound fasiglifam, a potential first-in-class GPR40 agonist for the treatment of Type 2 diabetes, demonstrating the study's primary endpoint of change from baseline in HbA1c at week 24 was met.[3] Study findings showed that fasiglifam significantly improved glycemic control with low incidence of hypoglycemia and statistically significant reductions in HbA1c, compared with placebo, at 24 weeks in patients with Type 2 diabetes inadequately controlled by diet and exercise.[4]

EXAMINE Data

Results demonstrated that the EXAMINE exploratory adjudicated CV composite endpoint of all-cause mortality, nonfatal myocardial infarction, nonfatal stroke, urgent revascularization due to unstable angina, and hospitalization for heart failure occurred at similar rates in the alogliptin and placebo groups (16.0% vs. 16.5%; hazard ratio, 0.98; 95% confidence limits [CL] of 0.86 to 1.12). For the post hoc composite endpoint of cardiovascular death and hospitalization for heart failure, there was no difference in event rates between the alogliptin and placebo groups (7.4% vs. 7.5%; hazard ratio, 0.98; 95% confidence limits [CL] of 0.82 to 1.20). Rates of hospitalization for heart failure were similar in the alogliptin versus placebo groups for both composite endpoints. Among other published DPP-4i CV safety outcomes trials, EXAMINE was the only trial to have evaluated Type 2 diabetes patients at high-risk for major adverse cardiac events (MACE) due to recent acute coronary syndrome (ACS).[5] Results of the global alogliptin EXAMINE trial were recently published in the New England Journal of Medicine.[6]

“As physicians, it is critical that we understand the impact of treating high risk patient groups such as those evaluated by the EXAMINE trial,” said Simon Heller, D.M., EXAMINE Steering Committee member. “Many Type 2 diabetes patients today are also living with cardiovascular disease and these additional findings on heart failure hospitalizations will provide important clinical insights for physicians helping patients manage their diabetes.”

Fasiglifam Data

The presentation entitled “Efficacy and safety of fasiglifam (TAK-875), a GPR40 selective agonist, in Japanese Type 2 diabetes mellitus patients: a Phase 3, double-blind, placebo controlled, comparative study” includes findings from the CCT-003 study, which evaluated the efficacy and safety of the investigational compound fasiglifam 25 mg and 50 mg, administered once daily before breakfast for 24 weeks, in Japanese patients with Type 2 diabetes inadequately controlled by diet and exercise.[7] Findings met the study's primary endpoint achieving a statistically significant change from baseline in HbA1c compared to placebo (p<0.0001).[8] The difference in the least-square means in HbA1c versus placebo was -0.75% (95% CI: -0.985 to -0.521) in the fasiglifam 25 mg group and -1.01% (95% CI: -1.244 to -0.777) in the fasiglifam 50 mg group.[9] There were no significant differences in incidence of adverse events between the fasiglifam groups and the placebo group.[10]

“We are pleased to present the Phase 3 findings from this study on fasiglifam, which further help to demonstrate the clinical profile of this potential new option for Type 2 diabetes,” said Ajay Ahuja, M.D., vice president, Global Medical Affairs, Takeda. “Takeda has built a strong foundation and maintained a robust focus in diabetes for more than 20 years, and presenting a total of seven abstracts at EASD with the scientific community underscores our dedication to addressing the needs of this growing patient population.”