Amgen today announced that a new analysis showed lowering low-density lipoprotein cholesterol (LDL-C) levels with Repatha (evolocumab) reduced the risk of cardiovascular events in a sub-group of patients with a history of stroke from the Repatha cardiovascular outcomes study (FOURIER). No new safety concerns were identified in this cohort of more than 5,000 patients. Detailed results were presented today in a Late-Breaking Clinical Trials session at the European Society of Cardiology (ESC) Congress 2017 in Barcelona, Spain.
“The clinical benefits of PCSK9 inhibition in stroke patients have not been previously reported. The reduction in cardiovascular event risk in this analysis is similar to what we saw in the broader 27,564-patient FOURIER study, supporting Repatha’s role in reducing the risk of future cardiovascular events for patients with a history of stroke,” said Terje Pedersen, professor emeritus, Department of Endocrinology, Morbid Obesity and Preventive Medicine at the University of Oslo Institute of Clinical Medicine, Oslo, Norway.
Nineteen percent of patients in the Repatha cardiovascular outcomes study had a prior history of non-hemorrhagic stroke (n=5,337). In this analysis, stroke patients treated with Repatha experienced a 56 percent mean reduction in LDL-C levels, compared to placebo (median LDL-C level of 29 mg/dL for patients on Repatha versus median LDL-C of 89 mg/dL for placebo;p<0.001).
In this analysis, the hazard ratio of Repatha compared to placebo for the composite primary endpoint, which included hospitalization for unstable angina, coronary revascularization, heart attack, stroke or cardiovascular death, was 0.85 (95 percent CI, 0.72-1.00; p=0.047). The hazard ratio of Repatha compared to placebo for the secondary composite endpoint of heart attack, stroke or cardiovascular death was 0.89 (95 percent CI, 0.74-1.08). The hazard ratios of Repatha compared to placebo for coronary revascularization, heart attack, stroke and cardiovascular death were 0.68 (95 percent CI, 0.52-0.90), 0.74 (95 percent CI, 0.55-1.00), 0.90 (95 percent CI, 0.68-1.19) and 1.11 (95 percent CI, 0.80-1.56), respectively.
“The cardiovascular outcomes study FOURIER unequivocally showed that lowering LDL-C with Repatha results in a powerful risk reduction for patients at high risk of a cardiovascular event,” said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. “The fact that we were able to detect a meaningful reduction in the risk of cardiovascular events in the much smaller sub-group of stroke patients is remarkable and demonstrates the importance of the intensive LDL-C lowering Repatha provides for patients with established atherosclerotic cardiovascular disease.”
In the sub-group of patients with a history of stroke, there were no notable differences in the overall rate of adverse events, serious adverse events or adverse events leading to study drug discontinuation. Rates of adjudicated new onset diabetes (2.1 percent Repatha; 2.0 percent placebo), cataract (1.0 percent Repatha; 0.8 percent placebo), and neurocognitive adverse events (1.0 percent Repatha; 1.0 percent placebo) were similar between the two arms.
Primary Analysis of the Repatha Cardiovascular Outcomes Trial
The primary analysis included 27,564 patients with established cardiovascular disease. 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 low-density lipoprotein cholesterol (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 and simultaneously published in the New England Journal of Medicine.
Repatha Cardiovascular Outcomes (FOURIER) Study Design
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 optimized statin dose. Optimized 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.
About Repatha (evolocumab)
Repatha (evolocumab) is a human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9). Repatha binds to PCSK9 and inhibits circulating PCSK9 from binding to the low-density lipoprotein (LDL) receptor (LDLR), preventing PCSK9-mediated LDLR degradation and permitting LDLR to recycle back to the liver cell surface. By inhibiting the binding of PCSK9 to LDLR, Repatha increases the number of LDLRs available to clear LDL from the blood, thereby lowering LDL-C levels.1
Repatha is approved in more than 50 countries, including the U.S., Japan, Canada and in all 28 countries that are members of the European Union. Applications in other countries are pending.
För mer information, vänligen kontakta:
Maria Eriksson Svensson, medicinsk chef, Amgen Sverige, tel: 076-1099440