Nexletol shows CLEAR benefit in cardiovascular outcome trial

New data for Esperion’s cholesterol lowering daily pill Nexletol, used when statins are not working in people at risk of a heart attack, could inject some momentum into the drug’s slow rollout.

Nexletol (bempedoic acid) was approved as an alternative to statins in 2020 as the first drug in the ATP Citrate Lyase (ACL) inhibitor class, and was once tipped as a future blockbuster, although sales have barely taken off since then, making just $56 million in US sales last year.

Esperion has been looking to the results of the phase 3 CLEAR Outcomes study to boost take-up, adding data showing that it could reduce major cardiovascular adverse events (MACE) to previous data showing it was effective at reducing LDL-cholesterol.

The company had already signalled that the results of the study were positive last December, and over the weekend reported the data at the American College of Cardiology (ACC) congress where clinicians got a look at the data, headlined by a 13% reduction in the risk of MACE compared to placebo.

The results – which were simultaneously published in the New England Journal of Medicine – showed that the difference was statistically significant in the 14,000-patient study, and backed up by a 23% reduced risk of myocardial infarction and a 19% reduction in the need for coronary revascularisation procedures.

All participants had LDL levels of 100 mg/dL or higher at baseline and either a previous cardiac event or other risk factors for heart disease, and were unable to tolerate statins or reach target doses with the drugs.

ESPERION said Nexletol and sister product Nexlizet (bempedoic acid and ezetimibe) are the only LDL-cholesterol lowering therapies since statins to “reduce hard ischaemic events in a broad population of both primary prevention and secondary prevention patients.”

A NEJM editorial also described the results as compelling, although Esperion shares were largely unmoved by the data reveal, suggesting investors may have been hoping for a stronger efficacy signal.

Cardiovascular outcome studies involving statins have shown MACE reductions of 40% to 50%, according to lead investigator Steve Nissen of the Cleveland Clinic, but also that the 13% reduction seen with Nexletol can still make a difference in the overall risk of cardiac events for patients who cannot tolerate statins.

“Most people can take statins, but some cannot,” commented Nissen. “This is the first study that directly addressed the problem of statin-intolerant patients. We achieved what we hoped we would get—a very positive result in a population of people who just could not tolerate statins.”

Esperion says it will now file for approval to update the label for Nexletol in the US, as well as in Europe, where the drug is sold by licensee Daiichi Sankyo. The company also says that it should be in line for $440 million in milestone payments should the new risk-reduction data get approved, including $300 million for inclusion on the EU label.

Photo by DESIGNECOLOGIST via Unsplash