Lilly Launches Head-to-Head Phase III CVOT Comparing Dual GIP/GLP-1 Agonist Tirzepatide Against Trulicity in Type 2 Diabetes Patients with Cardiovascular Disease

June 10, 2020 News /BioValleyBIOON/ --Eli LillyEli Lilly recently announced that the first patient has been dosed in SURPASS-CVOT, a Phase 3 cardiovascular outcomes trial evaluating the investigational dual GIP and GLP-1 receptor agonist tirzepatide (LY3298176). This head-to-head trial will assess the non-inferiority and superiority of tirzepatide compared with the market-leading GLP-1 receptor agonist Trulicity (dulaglutide) at a dose of 1.5 mg.

The SUSPASS-CVOT (NCT04255433) study included 12,500 patients with type 2 diabetes from 30 countries worldwide.Diabetesand patients with atherosclerotic cardiovascular disease (ASCVD). The primary endpoint was the time to first occurrence of MACE-3. MACE-3 is a composite endpoint of cardiovascular (CV) death, myocardial infarction, and stroke. Key secondary endpoints included the time to all-cause death and the time to occurrence of each component of the primary endpoint.Eli LillyThe trial is expected to take 4 years to complete.

David A. D'Alessio, M.D., Co-Chair of the study and Director of the Division of Endocrinology, Metabolism, and Nutrition at Duke University School of Medicine, and Stephen Nicholls, M.D., Ph.D., Academic Executive Committee representative for the study and Director of the Baker Heart and Diabetes Institute (formerly Victorian Heart Institute) at Monash University, stated: “Eli LillyA bold initiative is underway to compare tirzepatide with Trulicity, which has been proven to significantly reduce the risk of major adverse cardiovascular events (MACE). The SUSPESS-CVOT study will provide clinicians with critical evidence regarding patients with type 2 diabetes who also haveDiabetes"Among patients with cardiovascular disease, whether tirzepatide has the potential to surpass today’s best-in-class GLP-1 receptor agonist drugs in terms of cardiovascular outcomes."

Eli LillyDistinguished Medical Researcher Jeff Riesmeyer stated, “We continuously evaluateDiabetespatient needs, and is committed to research reflectingDiabetesInnovative Medicines Evolving the Standard of Care. “We are confident in the potential of tirzepatide to help patients with type 2 diabetes achieve benefits beyond glycemic control, and we look forward to the results of the SUPREME-CVOT.”

Trulicity (dulaglutide) is a glucagon-like peptide-1 (GLP-1) receptor agonist (RA) administered via once-weekly injection. It has been approved, in conjunction with diet and exercise, to improve glycemic control in adult patients with type 2 diabetes. In February 2020, Trulicity received U.S.FDAApproval of a new indication to reduce the risk of major adverse cardiovascular events (MACE) in adult patients with type 2 diabetes who have cardiovascular (CV) disease or multiple cardiovascular risk factors. Notably, this approval makes Trulicity the first type 2 diabetes medication approved to reduce MACE risk in both primary and secondary prevention populations.

GLP-1 RAs are a highly prominent class of medications for diabetes. GLP-1 RAs are not insulin; rather, they are a novel class of insulin secretagogues. Their mechanism of action is similar to that of the endogenous hormone GLP-1, promoting the body’s own insulin secretion in response to food intake, thereby offering potent glucose-lowering efficacy and a lower risk of hypoglycemia, while also havingWeight LossEfficacy and Advantages in Cardiovascular Benefits.

Since its U.S. market launch in 2014, Trulicity has become the most prescribed GLP-1 receptor agonist (GLP-1 RA). In addition to its proven glycemic efficacy and user-friendly delivery device, Trulicity is now also indicated to help reduce the risk of cardiovascular events in patients with type 2 diabetes. According to forecasts by the pharmaceutical market research firm EvaluatePharma, Trulicity’s sales are projected to reach $7.13 billion in 2024, making it the best-selling antidiabetic medication worldwide.

Currently,Eli LillyHigh-dose formulations of Trulicity (3 mg and 4.5 mg) are also under development. Data from the Phase III AWARD-11 trial in patients with type 2 diabetes demonstrated that the higher doses (3 mg and 4.5 mg) achieved significantly greater efficacy in lowering blood glucose and reducing body weight compared with the approved dose (1.5 mg). These data suggest that higher doses of Trulicity have the potential to provide clinicians with an additional therapeutic option for patients with type 2 diabetes who require further glycemic control due to the natural progression of the disease.

Tirzepatide is composed ofEli LillyA developed macromolecular polypeptide drug that acts as a dual agonist of the gastric inhibitory polypeptide (GIP) receptor and the glucagon-like peptide-1 (GLP-1) receptor. Both GIP and GLP-1 are gut-secreted hormones capable of promoting insulin secretion. A series of data presented at the 79th American Diabetes Association (ADA) Scientific Sessions in 2019 demonstrated that, in patients with type 2 diabetes, tirzepatide improved markers of β-cell function and insulin sensitivity, significantly reduced blood glucose levels, significantly reduced body weight, alleviated gastrointestinal side effects, and simultaneously improved markers of non-alcoholic steatohepatitis (NASH).

Based on the search results from the U.S. Clinical Trials Database, those involving tirzepatideClinical TrialUp to 29 trials, including 10 Phase III studies. These trials cover type 2 diabetes (Phase III), obesity (Phase III), and NASH (Phase II). Currently, tirzepatide has yielded exciting data in controlling blood glucose levels and reducing body weight in patients with type 2 diabetes, positioning it as a potential game-changer in this field.Eli LillyTirzepatide is expected to hit the market in 2022.

Currently,Eli LillyThe pipeline also includes a GIP/GLP/glucagon triple agonist currently in Phase I clinical trials, which is expected to enter Phase II clinical development this year. Existing data suggest that multi-receptor agonists demonstrate superior efficacy in lowering blood glucose and reducing body weight compared to pure GLP-1 agonists. Analysts have pointed out that multi-target receptor agonists will be a key focus in the field of diabetes in 2020. (Bioon.com)

Original Source: First Patient Dose Delivered for Lilly’s Tirzepatide Cardiovascular Outcomes Trial