Bempedoic Acid Wins FDA Approval for Reducing Cardiovascular Risk in Primary, Secondary Prevention

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The FDA's approval of the label expansion for bempedoic acid to include cardiovascular risk reduction is based on data from the CLEAR Outcomes trial.

The US Food and Drug Administration has approved label expansions for bempedoic acid (Nexletol) and bempedoic acid with ezetimibe (Nexlizet) to include primary and secondary prevention of cardiovascular risk, according to an announcement by Esperion.

Announced on March 22, 2024, the FDA’s decision is based on the CLEAR Outcomes trial and makes bempedoic acid the first LDL-lowering non-statin agent to receive a primary prevention indication. According to Esperion, the label expands the potential patient population for the non-statin LDL-lowering agent to approximately 70 million US adults.

“These approvals expand the accessibility of our highly effective drugs to primary prevention patients, or to those who are at high risk of having a cardiovascular event, but who have not yet had one,” said Sheldon Koenig, president and chief executive officer of Esperion. “These approvals also eliminate the statin use requirement, allowing patients to take NEXLETOL or NEXLIZET either with or without a statin, which significantly reduces previously existing prescribing limitations. We are confident these approvals position NEXLETOL and NEXLIZET as the non-statins of first choice within the cardiovascular risk reduction treatment paradigm.”

The cardiovascular risk reduction label expansion for bempedoic acid represents a long-awaited victory for the agent, which received its initial approval for lowering LDL-C in February 2020 based on data from a pair of clinical trials. However, despite demonstrating efficacy for LDL-C-lowering in a phase 3, many providers were left with questions related to its ability to reduce cardiovascular risk. These questions were answer in March 2023 with the release of data from the CLEAR Outcomes trial.

The headlining item from the American College of Cardiology’s 2023 Annual Scientific Sessions, the long-awaited CLEAR Outcomes trial provided evidence of a cardiovascular risk reduction achieved with use of bempedoic acid in 13,970 statin-intolerant patients. The trial leveraged a 4-point major adverse cardiovascular events (MACE), which included cardiovascular death, nonfatal myocardial infarction (MI), nonfatal stroke, or coronary revascularization, as the primary outcome of tiniest.

Simultaneously published in the New England Journal of Medicine, results of the study suggested primary endpoint event was significantly lower with bempedoic acid (11.7%) than with placebo therapy (13.3%) (Hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.79-0.96; P=.004). Investigators pointed out the analyses also indicated use of bempedoic acid was associated with reductions in the incidences of a composite of death from cardiovascular causes, nonfatal stroke, or nonfatal MI (HR, 0.85; 95% CI, 0.76-0.96; = .006), fatal or nonfatal MI (HR, 0.77; 95% CI, 0.66-0.91; = .002); and coronary revascularization (HR, 0.81; 95% CI, 0.72-0.92; = .001).

In June 2023, Steve Nissen, MD, presented data at the 83rd Scientific Sessions of the American Diabetes Association from a 4206-patient primary prevention subgroup within the trial. Data from this group indicated use of bempedoic acid was associated with a 30% reduction in relative risk of a primary endpoint event in adjusted analyses, which included a median follow-up of 39.9 months (aHR, 0.70; 95% CI, 0.55-0.89; P = .002).

In January 2024, the community received further insight into the apparent benefits of use on cardiovascular risk, with investigators publishing a prespecified analysis detailing the effect of the agent on total cardiovascular events. Results of this analysis, which were published in JAMA Cardiology, suggested use was associated with relative risk reductions of 20%, 17%, 31%, and 32% for 4-point MACE, 3-point MACE, MI, and coronary revascularization.

“We are thrilled with these significantly expanded labels and look forward to being able to now reach millions more patients with our life-saving drugs. In anticipation of these approvals, we have significantly ramped up our sales force, developed a powerful suite of new promotional materials, created a bold new consumer campaign, enhanced our patient support programs, and continued working with payers to ensure improved patient access,” Koenig added.