MISSISSAUGA, ON (Nov.16, 2016) – Amgen Canada Inc. today announced new detailed results from GLAGOV (GLobal Assessment of Plaque ReGression with a PCSK9 AntibOdy as Measured by IntraVascular Ultrasound), a Phase 3 coronary intravascular ultrasound imaging trial. The study showed that adding Repatha™ (evolocumab) to optimized statin therapy resulted in statistically significant regression of atherosclerosis in patients with coronary artery disease (CAD). These data were presented yesterday at a Late-Breaking Clinical Trials Session of the American Heart Association (AHA) Scientific Sessions 2016 and simultaneously published in the Journal of the American Medical Association.
The GLAGOV study evaluated whether Repatha, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor for the treatment of certain patients with elevated low-density lipoprotein cholesterol (LDL-C), would modify atherosclerotic plaque build-up in the coronary arteries of patients already treated with optimized statin therapy, as measured by intravascular ultrasound (IVUS) at baseline and week 78.
This study, using intravascular ultrasound imaging to measure the change in size of atherosclerotic plaque over time, shows that that maximal LDL-C reduction with Repatha on top of optimized statin therapy reduces the progression of coronary atherosclerotic disease. Nearly two-thirds of patients on Repatha in this trial, the majority of whom were already on high to moderate intensity statin therapy at baseline, experienced a reduction in plaque burden.
The study met its primary objective showing that treatment with Repatha resulted in a statistically significant regression from baseline in per cent atheroma volume (PAV), which is the proportion of arterial lumen occupied by plaque. Patients in the Repatha arm experienced a 0.95 per cent decrease versus baseline in PAV compared with an increase of 0.05 per cent versus baseline in patients receiving optimized statin therapy plus placebo (Repatha arm p<0.0001; placebo arm p=0.78). The difference between the two arms was statistically significant (p<0.0001). In addition, adding Repatha yielded plaque regression in PAV for a greater percentage of patients than for those receiving placebo (64.3 per cent versus 47.3 per cent, respectively, p<0.0001). At baseline, 98 per cent of patients in both arms were on high to moderate intensity statin therapy.
Patients in the Repatha arm experienced a mean decrease in normalized total atheroma volume (TAV), which is a measure of plaque volume, of 5.8mm3 compared with 0.9mm3 seen in the placebo arm (Repatha arm p<0.0001; placebo arm p=0.45). The difference between the two arms was statistically significant (p<0.0001). Additionally, adding Repatha yielded plaque regression in TAV for a greater percentage of patients than placebo (61.5 per cent versus 48.9 per cent, respectively, p=0.0002).
“This ultrasound imaging study examined whether Repatha would show additional plaque regression in addition to optimal statin therapy,” said Dr. Todd J. Anderson, Director at Libin Cardiovascular Institute of Alberta, and Professor at the University of Calgary. “The findings suggest that the addition of this therapeutic option to optimized statin therapy can indeed reduce atherosclerotic plaque build-up in the coronary arteries.”
At baseline, patients had a mean LDL-C of 2.39 mmol/L across both treatment arms. During 78 weeks of treatment, the time-weighted mean LDL-C level was 0.95 mmol/L in the Repatha arm, which represents a reduction of 59.8 per cent, compared with 2.40 mmol/L in the placebo arm. At week 78, the mean LDL-C in the Repatha arm was 0.75 mmol/L, which represents a 68.0 per cent decrease from baseline, and in the placebo arm was 2.33 mmol/L.
No new safety concerns were identified in the GLAGOV trial. The incidence of treatment-emergent adverse events (TEAE) was comparable among both groups (67.9 per cent Repatha; 79.8 per cent placebo). Adverse events of clinical importance reviewed in this study included myalgia (7.0 per cent Repatha; 5.8 per cent placebo), new diagnosis of diabetes mellitus (3.6 per cent Repatha; 3.7 per cent placebo), neurocognitive events (1.4 per cent Repatha; 1.2 per cent placebo) and injection site reactions (0.4 per cent Repatha; 0.0 per cent placebo). In the GLAGOV study, binding antibodies were rarely observed (0.2 per cent [1 patient] in the Repatha-treated arm) and no patients tested positively for neutralizing antibodies.
GLAGOV Study Design
GLAGOV (GLobal Assessment of Plaque ReGression with a PCSK9 AntibOdy as Measured by IntraVascular Ultrasound) is a Phase 3, multicentre, double-blind, randomized, placebo-controlled trial designed to evaluate the effect of Repatha on the change in burden of CAD in 968 patients undergoing clinically indicated coronary angiogram and on optimized background statin therapy.
Patients were required to have been treated with a stable statin dose for at least four weeks and to have a LDL-C ≥ 2.07 mmol/L or between 1.55 and 2.07 mmol/L with one major cardiovascular risk factor (defined as non-coronary atherosclerotic vascular disease, myocardial infarction or hospitalization for unstable angina in the preceding two years or type 2 diabetes mellitus), or three minor cardiovascular risk factors (defined as current cigarette smoking, hypertension, low levels of HDL cholesterol, family history of premature coronary heart disease, high sensitivity C-reactive protein (hs-CRP) ≥ 2mg/L or age ≥50 years in men and 55 years in women).
Patients were randomized 1:1 into two treatment groups to either receive monthly Repatha 420 mg or placebo subcutaneous injections. Optimized statin therapy was defined as at least atorvastatin 20 mg daily or equivalent, titrated to achieve LDL-C reduction per regional guidelines. Highly effective statin therapy (equivalent to atorvastatin 40 mg daily or higher) was recommended for all patients. Those patients with LDL-C >2.59 mmol/L not taking highly effective statin therapy, required investigators’ attestation as to why such doses were not appropriate. The primary endpoint was change in PAV from baseline to week 78 compared to placebo, as determined by IVUS. IVUS is a high-resolution imaging tool that allows for the quantification of coronary atheroma in the coronary arteries.
Secondary endpoints included PAV regression (any reduction from baseline); change in (TAV) from baseline to week 78; and regression (any reduction from baseline) in TAV.
About Repatha™ (evolocumab)1
Repatha (evolocumab) is a fully human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9).Repatha binds selectively and with high affinity to PCSK9, and inhibits circulating PCSK9 from binding to the low-density lipoprotein (LDL) receptor (LDLR) on the liver cell surface, thus preventing PCSK9-mediated LDLR degradation therefore increasing the number of LDLR available to clear LDL, thereby lowering serum LDL-C levels.
Repatha is indicated as an adjunct to diet and maximally tolerated statin therapy in adults with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease (CVD), who require additional lowering of LDL-C; and as an adjunct to diet and other LDL-lowering therapies in adults and adolescent patients aged 12 years and over with homozygous familial hypercholesterolemia (HoFH), who require additional lowering of LDL-C. The effect of Repatha on cardiovascular morbidity and mortality has not been determined.
About Amgen Cardiovascular
Building on more than three decades of experience in developing biotechnology medicines for patients with serious illnesses, Amgen is dedicated to addressing important scientific questions to advance care and improve the lives of patients with cardiovascular disease, the leading cause of morbidity and mortality worldwide.2 Amgen's research into cardiovascular disease, and potential treatment options, is part of a growing competency at Amgen that utilizes human genetics to identify and validate certain drug targets. Through its own research and development efforts, as well as partnerships, Amgen is building a robust cardiovascular portfolio consisting of several approved and investigational molecules in an effort to address a number of today's important unmet patient needs, such as high cholesterol and heart failure.
About Amgen Canada Inc.
With main operations located in Mississauga, Ont.’s vibrant biomedical cluster, and its research facility in Burnaby, B.C., Amgen Canada has been an important contributor to advancements in science and innovation in Canada since 1991. Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology. Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people’s lives. To learn more about Amgen Canada, visit www.amgen.ca.
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