Amgen announced that the 27,564-patient Repatha (evolocumab) cardiovascular outcomes study, FOURIER, established that maximally reducing low-density lipoprotein cholesterol (LDL-C) levels with Repatha, beyond what is possible with the current best therapy alone, leads to a further reduction in major cardiovascular events, including heart attacks, strokes and coronary revascularizations.
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 robust benefit in this objective measure started as early as six months and continued to accrue through the median 2.2 years of the study. In fact, the magnitude of the risk reduction in the hard MACE composite endpoint grew over time, from 16 percent in the first year to 25 percent beyond the first year, Amgen said.
Patients on Repatha experienced a reduction in the risk of heart attack (27 percent, nominal p<0.001), stroke (21 percent, nominal p=0.01) and coronary revascularization (22 percent, nominal p<0.001). Consistent with recent trials of more intensive LDL lowering, there was no observed effect on cardiovascular mortality.1-5 Similarly, there was no observed effect on hospitalization for unstable angina. In an exploratory analysis, the relative risk reduction for fatal and non-fatal heart attack or stroke was 19 percent in the first year (p=0.003) and 33 percent beyond the first year (p<0.00001).
"We now show for the first time in a dedicated outcomes study that decreasing LDL cholesterol with PCSK9 inhibition results in clinically meaningful cardiovascular benefit," 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. "These benefits were achieved with lowering LDL cholesterol down to a median of 30 mg/dL, which is well below current targets, and the magnitude of risk reduction increased the longer patients were on therapy. These results support the need for long-term, vigorous LDL cholesterol reduction in our patients with cardiovascular disease."
When added to statin therapy, Repatha reduced LDL-C from a median of 92 to 30 mg/dL, a reduction of 59 percent at week 48, which was sustained throughout the trial. At 48 weeks, the LDL-C was reduced to at least 25 mg/dL in 42 percent of patients treated with Repatha, as compared with <0.1 percent in the placebo group (p<0.001). Additionally, treatment with Repatha had favorable effects on other lipid parameters.
"This is a game changer for high-risk patients. Even though these patients were optimally treated with the latest therapies, they were still at high risk for an additional cardiac event. It's remarkable to see such a large impact in reducing cardiac events given that this patient population was only on Repatha for about two years," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "The absolute benefit will be even greater than what we observed in the Repatha outcomes trial, since the cardiovascular event rate in clinical practice is about 2-3 times higher than what is typically reported in a rigorously controlled outcomes trial."
To underscore the company's conviction around the outcomes results, Amgen will offer additional contracting options in the U.S. to payers willing to remove access barriers. These options include one that offers a refund of the cost of Repatha for all of their eligible patients who have a heart attack or stroke. In addition, Amgen will continue to offer innovative contracts that provide reasonable budget predictability to help address budget impact concerns raised by payers.