Repatha Shows Benefit in Coronary Artery Disease

Amgen recently announced findings from a phase 3 clinical trial of the PCSK9 inhibitor Repatha (evolocumab) in patients with coronary artery disease.

It was discovered that Repatha, in conjunction with statin therapy, was able to significantly reduce atherosclerosis in these patients.

Amgen presented results from the GLAGOV phase 3 coronary intravascular ultrasound imagining trial at the American Heart Association Scientific Sessions 2016. This study examined whether adding Repatha would reduce atherosclerostic plaque in the coronary arteries among patients receiving statin treatment.

Repatha is a human monoclonal antibody PCSK9 inhibitor that treats patients with high low-density lipoprotein cholesterol (LDL-C). The drug binds to PCSK9 to prevent it from circulating and binding with LDL receptors. By preventing the binding of PCSK9 to LDL receptors, Repatha increases the amount of receptors that are able to clear LDL, which then lowers LDL levels in the blood.

"The cardiovascular community began conducting imaging studies with LDL-C therapies to measure slowing of atherosclerotic disease progression. This study shows that maximal LDL-C reduction with Repatha can actually regress coronary atherosclerotic disease compared to statins alone," said Sean E. Harper, MD, executive vice president of Research and Development at Amgen. "In fact, nearly two-thirds of patients on Repatha in this trial, the vast majority of whom were already on high to moderate intensity statin therapy at baseline, experienced a reduction in plaque burden."

Included in the study were 968 patients with coronary artery disease, with 98% of these patients already on a regimen of moderate-intensity statin therapy.

Amgen reported that the study met its primary objective in showing that Repatha was able to cause a significant regression from baseline in atheroma volume (PAV), which is the amount of arterial lumen occupied by plaque.

Patients taking Repatha had a 0.95% reduction in PAV, compared with an increase of 0.05% in patients taking statin plus placebo. The addition of Repatha was also seen to reduce PAV for 64.3% of patients, while only 47.3% of patients in the placebo group achieved a reduction.

Patients taking Repatha also had a decrease in normalized total atheroma volume (TAV) plaque volume, of 5.8mm³ compared with 0.9mm³ in the placebo group. Patients in the Repatha group also experienced a 61.5% plaque regression in TAV compared with 48.9% reduction in patients in the placebo group.

"Based on previous studies, we did not know if GLAGOV would show additional plaque regression at LDL-C levels below 60 mg/dL," said Stephen J. Nicholls, MD, PhD, professor of Cardiology and deputy director, South Australian Health & Medical Research Institute, Adelaide, Australia. "One of the most compelling results from GLAGOV is the continued reduction of plaque at LDL-C levels well below commonly accepted thresholds."

At week 78, the mean LDL-C level in the Repatha group decreased by 68% (29mg/dL) compared with the placebo group (90 mg/dL).

An analysis also evaluated the amount of plaque reduction seen in 144 patients with LDL-C levels less than 70 mg/dL at baseline. Investigators discovered that patients taking Repatha had the most significant reduction in plaque compared with placebo (-1.97%versus -0.35%, respectively, p<0.0001).

Patients taking Repatha in this subset had plaque regression of 81.2% compared with a reduction of 48% in patients taking the placebo, according to Amgen.

Additionally, no additional safety concerns were discovered, and adverse events were comparable among all patients. Adverse events included myalgia, newly diagnosed diabetes, neurocognitive events, and injection sight reactions.

Investigators rarely saw binding antibodies, and no patients tested positive for neutralizing antibodies, Amgen reported.

While the GALGOV trial was not designed to determine cardiovascular effects, another analysis found that positively-adjudicated major cardiovascular events in 12.2% and 15.3% of patients taking Repatha and the placebo, respectively. Common events included coronary revascularization and myocardial infarctions, and other events occurred in less than 0.8% of patients in each group.

“The compelling data from GLAGOV remove any scientific doubt about the ability of Repatha to lower LDL-C and the impact it has on the critical underlying disease process,” Dr Harper concluded. “We remain concerned that many patients are experiencing barriers to accessing Repatha, despite their physician's treatment recommendations. We look forward to our outcomes study, FOURIER, and will continue to work with payers to improve access for patients who need additional LDL-C lowering.”