Phase III BEST trial of THR 1442 shows efficacy in type 2 diabetes with CV risk.- Theracos

Phase III BEST trial data shows that THR 1442 (bexagliflozin) from Theracos, lowers weight, blood pressure and glycated haemoglobin (HbA1c) relative to placebo in patients with type 2 diabetes at high risk for cardiovascular (CV) events. The data also showed that the drug was noninferior for the composite CV safety endpoint of major CV events (CV death, myocardial infarction, stroke) plus unstable angina, seen in 7.9% of patients on bexagliflozin and 10.1% of those on placebo.

The BEST study included 1700 individuals (30% women) with type 2 diabetes who were aged 40 years and older (mean 64 years), with an HbA1c of 7.5–11.0% and an estimated glomerular filtration rate of at least 45 mL/min per 1.73 m2. Patients were divided into those with established atherosclerotic vascular disease (63%), those with a history of heart failure (HF; 14%), and those aged 55 years and older with at least two other CV risk factors (23%), and were then randomly assigned on a 2:1 basis to receive bexagliflozin 20 mg once daily or placebo.

The difference between the groups started early and persisted for up to 3 years, with similar results observed among a subgroup of patients receiving insulin at baseline (n=834). A number of secondary endpointswere also assessed, and bexaglifloxin was associated with significantly greater weight loss at week 48 among participants with a baseline BMI above 25 kg/m2 (n=1378), at 3.0 versus 0.4 kg with placebo, and a significantly greater reduction in systolic blood pressure among those with a baseline level of at least 140 mmHg (n=663), at 9.8 versus 6.9 mmHg. For time to first hospitalization with HF, bexagliflozin was noninferior to placebo (hazard ratio = 0.63). Bexagliflozin was well-tolerated and had a similar adverse event (AE) profile to that of other SGLT2 inhibitors. Serious AEs occurred in 33.0% of people in the bexagliflozin group and 36.7% of those in the placebo group, with treatment discontinuations due to AEs reported in 8.4% and 8.5%, respectively. The data were presented at the virtual ADA 80th Scientific Sessions.