-Newly released clinical trial data show expected reductions in stroke and heart attack, but mortality benefit assumed in original cost-effectiveness analysis not found- 
Boston, Mass., June 13, 2017- Following release of new clinical evidence in March 2017, the Institute for Clinical and Economic Review (ICER) has developed a New Evidence Update to its 2015 review of the comparative clinical effectiveness and value of PCSK9 inhibitors for management of high cholesterol. The comparative clinical effectiveness portion of the update is now available.

The update covers new information issued since the 2015 ICER report on PCSK9 inhibitors, including an analysis of recently-released evidence from the FOURIER trial of evolocumab.  These results showed that evolocumab combined with statins is effective in reducing the incidence of cardiovascular events such as heart attack and stroke, but did not show a statistically significant reduction in cardiovascular mortality. The cost-effectiveness analysis in ICER’s 2015 review had assumed a mortality benefit that was not found in the FOURIER study.

Based on those earlier analyses, ICER had recommended a value-based price benchmark of $5,404-$7,735 for annual treatment costs for PCSK9 inhibitors 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 the coming months ICER will release an updated economic analysis based on the FOURIER trial data that will include a revised, lower value-based price benchmark for evolocumab.

“At the time of our initial report on PCSK9 inhibitors, the ability of these drugs to dramatically lower cholesterol levels was obvious.  What remained unknown, and what was obviously of greatest importance to patients and clinicians, was the extent to which the lower cholesterol levels would ultimately help prevent strokes, heart attacks, and premature death,” noted Steven D. Pearson, MD, MSc, President of ICER.

“With data now available on these patient-centered outcomes from an important study of one of the two available drugs, and with insurers and others in the process of revisiting earlier coverage and pricing decisions, we felt it would be helpful to provide an update that summarizes our view of the implications of the new evidence for judgments of comparative clinical effectiveness.  We plan to release a second part of this update containing revised cost-effectiveness analyses and corresponding value-based price benchmarks in the near future,” Dr. Pearson added.

Amgen’s FOURIER trial included patients with ASCVD whose LDL-C levels had not met the target of 70mg/dL or lower with statin therapy alone.  ICER’s New Evidence Update therefore focuses on this subpopulation.  Significant new evidence on other subgroups included in ICER’s initial report, including those with familial hypercholesterolemia, has not yet emerged.

ICER’s 2015 report found the evidence at that time on the clinical benefit of PCSK9 inhibitors evolocumab (Repatha®, Amgen, Inc.) and alirocumab (Praluent®, Sanofi and Regeneron Pharmaceuticals) to be promising but inconclusive, citing benefit in LDL-C reduction but significant uncertainties around the eventual patient-centered benefits and harms. In particular, it was unclear the degree to which overall risk for cardiovascular events would be reduced by the dramatic reductions in LDL-C produced by these drugs.

Based on the new data from the FOURIER trial that fills in this gap in the evidence, ICER has updated its rating for the comparative clinical effectiveness of evolocumab in combination with statin therapy for this patient population to “comparable or better” than treatment with statins alone.  Longer-term studies are ongoing of the other available PCSK9, alirocumab, which may provide important new evidence to assess the relative clinical effectiveness of each PCSK9 inhibitor and of the class as a whole.

For more information about ICER’s review of PCSK9 inhibitors, please visit our website.

About ICER
The Institute for Clinical and Economic Review (ICER) is an independent non-profit research institute that produces reports analyzing the evidence on the effectiveness and value of drugs and other medical services. ICER’s reports include evidence-based calculations of prices for new drugs that accurately reflect the degree of improvement expected in long-term patient outcomes, while also highlighting price levels that might contribute to unaffordable short-term cost growth for the overall health care system.
ICER’s reports incorporate extensive input from all stakeholders and are the subject of public hearings through three core programs: the California Technology Assessment Forum (CTAF), the Midwest Comparative Effectiveness Public Advisory Council (Midwest CEPAC), and the New England Comparative Effectiveness Public Advisory Council (New England CEPAC). These independent panels review ICER’s reports at public meetings to deliberate on the evidence and develop recommendations for how patients, clinicians, insurers, and policymakers can improve the quality and value of health care. For more information about ICER, please visit ICER’s website.