Amgen has announced new data from the Repatha (evolocumab) cardiovascular outcomes trial (FOURIER), which showed that Repatha consistently and safely reduced cardiovascular events in patients with established cardiovascular disease regardless of baseline low-density lipoprotein cholesterol (LDL-C) level below or above 70 mg/dL. A separate analysis also demonstrated Repatha reduced cardiovascular events in patients being treated with maximum-intensity statin therapy. These results were presented during a late-breaker session at the 2017 National Lipid Association (NLA) scientific sessions.

"We now have additional evidence of the benefit of evolocumab in reducing cardiovascular event risk, even in patients starting with LDL-C levels below the most aggressive current guideline targets and in patients already on maximum-intensity statin therapy," said Marc S. Sabatine, M.D., M.P.H., chairman of the TIMI Study Group, the Lewis Dexter, MD, Distinguished Chair in Cardiovascular Medicine at Brigham and Women's Hospital, and Professor of Medicine, Harvard Medical School, Boston.

The two analyses compared clinical outcomes in patients stratified by baseline LDL-C above and below 70 mg/dL and in patients on maximum-intensity statin therapy, defined as atorvastatin 80 mg or rosuvastatin 40 mg daily, versus patients on less intense statin therapy.

"These results provide further evidence for patients with established cardiovascular disease who would otherwise be considered as being successfully managed to the most stringent treatment targets," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "Previously, physicians have debated the benefit of treating high-risk cardiovascular patients with baseline LDL-C levels below 70 mg/dL. The Repatha cardiovascular outcomes trial shows that even patients already at lower levels of baseline LDL-C are still at risk for a cardiovascular event, and the addition of Repatha can continue to safely lower these patients' cardiovascular risk by reducing their LDL-C levels beyond current targets."

In patients with a baseline LDL-C below 70 mg/dL (n=2,034), Repatha reduced the median baseline LDL-C from 65.5 mg/dL to 21.0 mg/dL. Repatha consistently reduced the risk of the composite primary endpoint, which included hospitalization for unstable angina, coronary revascularization, heart attack, stroke or cardiovascular death, regardless of whether baseline LDL-C was below or above 70 mg/dL (20 percent in patients with baseline <70 mg/dL; 14 percent in patients with baseline =70 mg/dL, P-interaction=0.65). The results were also consistent for the more robust, secondary composite endpoint of heart attack, stroke or cardiovascular death where patients with a baseline LDL-C less than 70 mg/dL experienced a 30 percent reduction in cardiovascular events and patients with a baseline LDL-C greater than or equal to 70 mg/dL experienced a 19 percent reduction in cardiovascular events (P-interaction=0.44).

In patients on maximum-intensity statins (n=7,533), Repatha reduced the median baseline LDL-C from 93 mg/dL to 32 mg/dL. Additionally, Repatha consistently reduced the risk of major cardiovascular events in patients on maximum-intensity and less intense statin therapy in both the composite primary endpoint (14 percent in patients on maximum-intensity statin therapy; 15 percent in patients on less intense statin therapy, P-interaction=0.88) and the composite secondary endpoint (22 percent in patients on maximum-intensity statin therapy; 19 percent in patients on less intense statin therapy, P-interaction=0.71).

In the two analyses, there were no differences in the rates of adverse events leading to discontinuation between treatment groups in patients who had a baseline LDL-C below 70 mg/dL (4.4 percent Repatha; 4.6 percent placebo) or in patients on maximum-intensity statin therapy (3.9 percent Repatha; 3.7 percent placebo).

Results from the primary analysis of the 27,564-patient Repatha cardiovascular outcomes study were also presented at the meeting. The study was statistically powered around the hard major adverse cardiovascular event (MACE) composite endpoint of first heart attack, stroke or cardiovascular death (key secondary composite endpoint) and found that adding Repatha to optimized statin therapy resulted in a statistically significant 20 percent (p<0.001) reduction in these events. The study also found a statistically significant 15 percent reduction (p<0.001) in the risk of the extended MACE composite (primary) endpoint, which included hospitalization for unstable angina, coronary revascularization, heart attack, stroke or cardiovascular death.

No new safety concerns were identified in this large clinical trial with roughly 60,000 patient-years of follow-up; this included the assessment of patients who achieved very low levels of LDL-C. The detailed results from the Repatha cardiovascular outcomes study were initially presented during a Late-Breaking Clinical Trials Session at the American College of Cardiology 66th Annual Scientific Session (ACC.17) and simultaneously published in the New England Journal of Medicine.

The 27,564-patient Repatha cardiovascular outcomes study, FOURIER (Further Cardiovascular OUtcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk), was a multinational Phase 3 randomized, double-blind, placebo-controlled trial, designed to evaluate whether treatment with Repatha in combination with statin therapy compared to placebo plus statin therapy reduces cardiovascular events. The primary endpoint was time to cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. The key secondary endpoint was the time to cardiovascular death, myocardial infarction or stroke.

Eligible patients with high cholesterol (LDL-C =70 mg/dL or non-high-density lipoprotein cholesterol [non-HDL-C] =100 mg/dL) and clinically evident atherosclerotic cardiovascular disease at more than 1,200 study locations around the world were randomized to receive Repatha subcutaneous 140 mg every two weeks or 420 mg monthly plus optimized statin dose; or placebo subcutaneous every two weeks or monthly plus effective statin dose. Effective statin therapy was defined as at least atorvastatin 20 mg or equivalent daily with a recommendation for at least atorvastatin 40 mg or equivalent daily where approved. The study was event driven and continued until 1,630 patients experienced a key secondary endpoint.