Phase III CLEAR study of Nexletol supports long term use in patients at high-risk of cardiovascular events and in those with diabetes, with data presented at ESC 2023.- Daiichi Sankyo

The results, presented at the European Society of Cardiology (ESC) Congress 2023, further support the long-term use of bempedoic acid in patients at high-risk of cardiovascular (CV) events and demonstrate particular benefit in those with diabetes.

A prespecified CLEAR Outcomes trial data analysis of the impact of treatment with bempedoic acid on total – first and subsequent – CV events in high-risk patients shows a 20% (HR 0.80 [95% CI 0.72, 0.89] p=0.0001) relative risk reduction (RRR) in the primary endpoint of a four-component composite of major CV adverse events (MACE-4), defined as death from CV causes, non-fatal myocardial infarction, non-fatal stroke or coronary revascularisation. The CLEAR Outcomes trial previously reported that treatment with bempedoic acid reduced the risk of a first MACE-4 CV event by 13% among those at high-risk of cardiovascular disease and unable or unwilling to take statins. This latest total events analysis, which followed-up patients for a median of 3.4 years, shows an increase in RRR of MACE-4 CV events when not only the first, but all events are considered. It is well documented that those that have experienced an adverse CV event are at higher risk of experiencing subsequent events. This data establishes the ongoing risk reduction of both first and subsequent CV events with bempedoic acid.

Results from the total events analysis presented today also included a: 17% RRR for the three-component composite of major adverse cardiovascular events (MACE-3) defined as death from CV causes, non-fatal myocardial infarction or non-fatal stroke; 31% RRR for non-fatal myocardial infarction and 22% RRR for coronary revascularisation. This new data establishes the benefits of long-term treatment with bempedoic acid in patients at high-CV risk.

An additional prespecified sub-analysis of the CLEAR Outcomes data focused specifically on the CV benefits by blood glucose status and risk of new-onset diabetes (NOD) when treated with bempedoic acid over a median 3.4 years follow-up. Those with diabetes are at greater risk of CVD and comprise a particularly high-risk group with an excess risk of CV events ranging from 25% for MACE-4 and 58% for MACE-3, compared to those whose blood glucose levels are within normal range. The sub-analysis results demonstrate that bempedoic acid both lowered LDL-C and reduced the risk of CV events with greater absolute benefit for those with diabetes. Furthermore, unlike statins, bempedoic acid did not increase HbA1c levels or the incidence of NOD (11.1% with bempedoic acid vs 11.5% with placebo) among those without diabetes.