— To reflect new clinical trial evidence, updated ICER value-based price benchmark for a year of treatment with evolocumab lowered to range between $1,725 and $2,242 —

Boston, Mass., September 11, 2017– Following the March 2017 release of clinical evidence on evolocumab (Repatha®, Amgen) from the FOURIER trial, the Institute for Clinical and Economic Review (ICER) has used those data to update its analysis of the drug’s long-term cost-effectiveness, and has posted these results along with an updated value-based price benchmark as the final component of ICER’s New Evidence Update on evolocumab.  Replacing earlier assumptions about treatment outcomes with actual clinical results, the updated analyses find evolocumab to be less cost-effective, leading to a lower calculated range for a value-based price that would align with the added benefit for patients.

“We have been eagerly awaiting ICER’s PCSK9 update based on the new study data,” said Chester B. Good, MD, MPH, Chair of the Medical Advisory Panel for Pharmacy Benefits at the Department of Veteran’s Affairs.  “This rigorous and independent evaluation of evidence, when combined with ICER’s cost-effectiveness analysis and pricing recommendations, helps us better understand the value of these drugs. We plan to use this report in our ongoing negotiations with manufacturers, as this update will help inform our efforts to secure a price that represents a fair deal for Veterans and the US taxpayer.”

Amgen’s FOURIER trial provided additional clarity on the longer-term outcomes of evolocumab for patients with atherosclerotic cardiovascular disease (ASCVD) whose low-density lipoprotein cholesterol (LDL-C) levels had not met an appropriate target of 70 mg/dL or lower with statin therapy alone.

In June 2017, ICER posted the section of the New Evidence Update addressing comparative clinical effectiveness, concluding that evolocumab combined with statin therapy is effective in reducing the incidence of cardiovascular events such as heart attack and stroke, but that evidence has failed to demonstrate a statistically-significant reduction in cardiovascular mortality.

“ICER’s 2015 report had assumed a mortality benefit based on data from statin trials linking reductions in LDL-C to cardiovascular death rates; however, no mortality benefit was observed in the FOURIER trial of actual clinical outcomes,” noted Steven D. Pearson, MD, MSc, ICER’s President.  “As a result, the updated cost-effectiveness analysis for this drug suggests that, in comparison with our earlier report, even deeper price discounts would be needed for the cost of evolocumab to align with the benefit it provides.  Evolocumab has the potential to benefit patients based on its ability to lower the risk of heart attack and stroke; but the price runs well above its demonstrated clinical benefit, contributing to the insurance barriers that threaten patients’ access.”

ICER’s initial review calculated the cost-effectiveness of PCSK9 agents as a class to be approximately $300,000 per quality adjusted life-year (QALY) gained, a level well above the widely-accepted cost-effectiveness threshold of $100,000-$150,000 per QALY.  The FOURIER trial did not show a reduction in cardiovascular mortality; however, ICER’s model, recognizing the possibility that the trial duration was too short to show this benefit, assumed some reduction in the rate of both fatal and nonfatal heart attacks and strokes.  Even when incorporating this assumed mortality benefit, the update found the cost-effectiveness of adding evolocumab to statin therapy to be approximately $1.3 million per QALY gained compared to statins alone.

Based on these findings, the value-based price benchmarks, or the range in which the cost of evolocumab would align with its benefit to patients, was found to be substantially lower than initially calculated, at $1,725 – $2,242 for annual treatment costs versus $5,300 – $7,600 in the initial report.  To meet the revised value-based price benchmark, evolocumab would need to be discounted 85% – 88% from the current wholesale acquisition cost (WAC) of $14,523 annually.

The updated economic conclusions apply only to use of evolocumab in patients with ASCVD whose LDL-C has not met an appropriate target.  Conclusions for other populations included in ICER’s initial report, including those with familial hypercholesterolemia, remain unchanged, as significant data on these populations has not yet emerged.

The release of ICER’s updated analyses follows posting of a research letter in JAMA in August of 2017. The article, authored by the group of researchers at the University of California at San Francisco who worked with ICER on the initial 2015 review, is based on the same economic model. There are, however, some critical differences between the analyses described in the research letter and those summarized in this evidence update, based on varying assumptions about mortality benefit, comparator therapies, and pricing. More detail on these distinctions is provided in ICER’s update.