Amgen announced data presented at the European Society of Cardiology (ESC) Congress 2016 showing Repatha (evolocumab) consistently reduced low-density lipoprotein cholesterol (LDL-C) in patients across cardiovascular (CV) risk subgroups or with familial hypercholesterolemia (FH).
"These analyses continue to shape the clinical evidence for Repatha and help to advance our understanding of its potential to benefit patients," said Sean E. Harper, M.D., executive vice president of research and development at Amgen. "The data at ESC provide further insights into the impact of Repatha on multiple patient populations who are at higher cardiovascular risk and are in need of additional treatment options."
Researchers looking at the "Efficacy of evolocumab in patients across ESC/EAS CV risk subgroups," categorized a total of 2,532 patients from three, 12-week phase 3 studies by the four ESC/European Atherosclerotic Society (EAS) risk criteria (very high, high, moderate and low). The analysis showed that treatment with Repatha 140 mg every two weeks or 420 mg monthly consistently reduced levels of LDL-C and other lipids from baseline to the mean of weeks 10 and 12 across all risk categories compared to placebo or ezetimibe controls. For example, among very high-risk patients, Repatha reduced LDL-C levels from baseline 65.2 percent more than placebo and 40.7 percent more than ezetimibe. The rates of overall adverse events were similar for the three groups, occurring in 43.1 percent, 50.5 percent and 40.8 percent of patients on Repatha, ezetimibe and placebo, respectively.
In another presentation, researchers looking at the "Long-term safety, tolerability and efficacy of evolocumab in patients with heterozygous familial hypercholesterolaemia," found that treatment with Repatha for 48 weeks resulted in persistent and marked LDL-C reductions in these patients. The analysis showed that Repatha plus standard of care (SoC) reduced LDL-C levels from baseline by 53.6 percent at 48 weeks (n=279), compared to a 2.1 percent increase for SoC alone (n=139). The pooled analysis included 440 patients with heterozygous familial hypercholesterolemia (HeFH) who completed Amgen's RUTHERFORD-1 (phase 2) or RUTHERFORD-2 (phase 3) trials and entered open-label extension trials (OSLER-1 or OSLER-2). Patients were randomized in the extension trials to receive SoC alone or Repatha plus SoC. Repatha was well tolerated in the extension studies with no new safety signals. The rates of overall adverse events were similar for the two groups, occurring in 80 percent of patients receiving Repatha and 67 percent of patients receiving SoC.
"These long-term data add to the growing body of evidence supporting Repatha's ability to meaningfully reduce LDL cholesterol levels in patients with familial hypercholesterolemia," said G. Kees Hovingh, M.D., Ph.D., Academisch Medisch Centrum, Vascular Medicine, Amsterdam, the Netherlands. "Familial hypercholesterolemia is an inherited condition that leads to high levels of LDL cholesterol from birth, and these high LDL cholesterol levels can result in increased risk for premature cardiovascular disease in patients with FH. This understanding is important for the HeFH patients in whom adequate control of their cholesterol levels with other currently approved lipid-lowering agents has been troublesome."
Additional data at the Congress included a Rapid Fire Abstract entitled, "Familial Hypercholesterolaemia Diagnosis: A Case of Missed Opportunity," which suggested that as few as 1 in 10 FH patients may be diagnosed. Patient-level data available in the Clinical Practice Research DataLink (CPRD), a UK-based general practice database, indicated a FH prevalence of 1.3 per 1,000 persons, which increased to 11.7 when missed diagnoses were counted.
Elevated LDL-C is an abnormality of cholesterol and/or fats in the blood and is recognized as a major risk factor for CV disease. In the US, there are approximately 11 million people with atherosclerotic cardiovascular disease (ASCVD) and/or FH who have uncontrolled levels of LDL-C over 70 mg/dL, despite treatment with statins or other cholesterol-lowering therapies. More than 60 percent of high-risk patients in Europe are still unable to adequately lower their LDL-C levels with statins or other currently approved lipid-lowering agents. Among very high-risk patients, the percentage is increased to more than 80 percent. It is estimated that less than one percent of people with FH (heterozygous and homozygous forms) in most countries are diagnosed.
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.
GLAGOV, the intravascular ultrasound study, is underway to determine the effect of Repatha on coronary atherosclerosis in approximately 950 patients undergoing cardiac catheterization to test the hypothesis of robust LDL-C reduction leading to a reduction or a change in the build-up of plaque in the arteries. Results from the GLAGOV study are expected in the second half of 2016.
The FOURIER outcomes trial is designed to evaluate whether treatment with Repatha in combination with statin therapy, compared to placebo plus statin therapy, reduces the risk of cardiovascular events in patients with high cholesterol and clinically evident cardiovascular disease, and completed patient enrollment in June 2015. The primary endpoint for the FOURIER trial is major cardiovascular events defined as the composite of cardiovascular death, myocardial infarction (MI), stroke, hospitalization for unstable angina or coronary revascularization. The key secondary end point is the composite of cardiovascular death, MI or stroke. The trial is planned to continue until at least 1,630 patients experience the secondary endpoint, thereby providing 90 percent power to detect a reduction of 15 percent in this endpoint. Top-line results from the approximately 27,500-patient event-driven FOURIER study are anticipated in first quarter of 2017.
Repatha is approved in 44 countries, including the US, Japan, Canada and in all 28 countries that are members of the European Union. Applications in other countries are pending.