Lilly targets regulatory filings after latest Phase III diabetes success for tirzepatide

Eli Lilly announced Thursday that the Phase III SURPASS-4 trial of tirzepatide in adults with type 2 diabetes who have increased cardiovascular (CV) risk met all of its primary and key secondary goals. "Tirzepatide delivered impressive results in this study, providing superior A1C reductions compared to insulin glargine – as well as the addition of significant weight loss," remarked senior investigator John Doupis.

The trial compared three tirzepatide doses to titrated insulin glargine in more than 2000 people with type 2 diabetes who have increased CV risk and are treated with between one and three oral antihyperglycaemic medicines. Eli Lilly noted that the mean baseline A1C in the study was 8.52% and baseline weight was 90.3 kg, while over 85% of participants had a history of CV events.

All doses achieve goals

Top-line results showed that all three doses of tirzepatide led to superior A1C and body weight reductions from baseline compared to insulin glargine. Specifically, the highest dose of tirzepatide led to an A1C reduction of 2.58% and reduced body weight by 11.7 kg, or 13%, at 52 weeks, compared to an A1C reduction of 1.44% and weight gain of 1.9 kg, or 2.2%, for insulin glargine.

Further, at the highest dose of tirzepatide, 90.7% of patients achieved an A1C of less than 7% and 43% hit the goal of an A1C of less than 5.7% percent, with respective rates in the insulin glargine group of 50.7% and 3.4%. Eli Lilly said that the overall safety profile of tirzepatide in the trial was consistent with the GLP-1 receptor agonist class, with gastrointestinal side effects being the most commonly reported adverse events. The company indicated that additional results will be presented at the European Association for the Study of Diabetes (EASD) annual meeting.

CV safety milestone hit

SURPASS-4 is the final global registration study for tirzepatide in type 2 diabetes to be completed, following positive results from SURPASS-1, SURPASS-2, SURPASS-3 and SURPASS-5. The company noted that a CV safety meta-analysis was conducted across the entire clinical programme, which consisted of 116 participants with adjudicated MACE-4, a composite endpoint of death from CV or undetermined causes, myocardial infarction, stroke and hospitalisation for unstable angina.

Eli Lilly said that comparing pooled tirzepatide versus pooled comparators, a hazard ratio of 0.81 was attained. The drugmaker explained that SURPASS-4 contributed the majority of the MACE-4 events for the CV safety meta-analysis, and within the study, a hazard ratio of 0.74 was observed. The company added that it plans to submit the full registration package to regulatory authorities by the end of 2021.

Tirzepatide, an investigational once-weekly dual GIP and GLP-1 receptor agonist, is also being investigated as potential treatments for non-alcoholic steatohepatitis and heart failure with preserved ejection fraction.

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