— Based on the results of the ODYSSEY Outcomes trial, ICER has calculated two updated value-based price benchmarks, net of rebates and discounts, for alirocumab in patients with a recent acute coronary event: $2,300-$3,400 per year if used to treat all patients who meet trial eligibility criteria, and $4,500-$8,000 per year if used to treat higher-risk patients with LDL cholesterol ≥ 100 mg/dL despite intensive statin therapy —

BOSTON, March 10, 2018 – The Institute for Clinical and Economic Review (ICER) today released a Preliminary New Evidence Update for alirocumab (Praluent®, Regeneron/Sanofi), based on results from the ODYSSEY outcomes trial presented at this weekend’s American College of Cardiology’s 2018 Scientific Session. Under ICER’s established protocols for accepting in-confidence data, an agreement with Regeneron and Sanofi allowed ICER to evaluate the new evidence and, working with a team of academic faculty from the University of California, San Francisco, to update its cost-effectiveness analyses and associated value-based price benchmarks for this drug. ICER’s value-based price benchmarks suggest a price range that aligns fairly with the added benefits of new treatment options for patients and the health care system. “These new data demonstrate that alirocumab not only lowers levels of bad cholesterol but can also reduce deaths among a patient population with a recent history of an acute coronary event,” said Steven D. Pearson, MD, MSc, President of ICER. “Patients in the trial whose cholesterol levels remained high despite intensive use of statin drugs had the most benefit from treatment, and we have performed a separate analysis of a value-based price benchmark for this patient subset. We commend the Regeneron and Sanofi team for seeking an independent assessment of the new data and an updated cost-effectiveness evaluation to inform future negotiations with payers on a fair, value-based price. Insurers and health systems may need to consider how to manage short-term affordability constraints given the large number of patients eligible for treatment. Nonetheless, we believe that responsible pricing aligned with value will generate reciprocal action from payers to ensure appropriate access for patients today while sustaining broader affordability for patients and the health system in the long term.” Given these new outcomes data confirming a mortality benefit for alirocumab, ICER is issuing this preliminary update to help inform new pricing and coverage negotiations between manufacturers and payers. We plan to issue a final New Evidence Update later this year, following the methodology and procedures defined on our website. ICER previously assessed the cost-effectiveness of alirocumab and evolocumab (Repatha®, Amgen) shortly after these drugs were first granted regulatory approval in the US in 2015, and performed a New Evidence Update for evolocumab in September 2017, following the release of outcomes data from the FOURIER trial.

Brief Summary of Updated Cost-Effectiveness Analysis Results We updated our estimates of the long-term cost-effectiveness of alirocumab based on data from the ODYSSEY Outcomes trial. This analysis was conducted in partnership with an independent research group at the University of California, San Francisco led by Dr. Kirsten Bibbins-Domingo and Dr. Dhruv Kazi. The team used the Cardiovascular Disease Policy Model, an established simulation model of cardiovascular disease (CVD) in the US population that systematically combines data from vital statistics, epidemiologic studies, clinical trials, and registries.

The greatest absolute benefit from therapies for CVD is expected to occur in patients at the highest risk. Results in the ODYSSEY Outcomes trial suggest greater benefit with alirocumab for patients with an LDL cholesterol (LDL-C) ≥ 100 mg/dL despite intensive statin therapy. We have calculated a value-based price range ($4,500-$8,000 per year), net of rebates and discounts, for this group using two different assumptions about mortality benefits. The higher end of the price range would likely apply if treated patients more closely approximate those in the clinical trial, and the lower end of the price range would likely apply if treated patients have the range of comorbidities – and therefore the risk of death from non-cardiovascular causes – of the broader population of patients in the US who have had an acute coronary event in the past year and have continued elevated LDL-C. A lower value-based price range ($2,300-$3,400 per year), net of rebates and discounts, would apply if the drug were used to treat all patients with an acute coronary event in the past year and an LDL-C ≥70 mg/dL.

Potential Budget Impact ICER will include a potential budget impact analysis as part of its final evidence update report. For this preliminary report we note only that estimates of the eligible population that are likely to be considered for PCSK9 inhibitor treatment have been contentious. Data on the secondary CVD prevention population in the US suggest that approximately 300,000 to 400,000 patients each year have an acute coronary event and also have an LDL-C ≥ 100 mg/dL. Not all of these patients are likely to be considered good candidates for PCSK9 inhibitor treatment by their clinicians, but even at the low end of this range, and at a price at the lower end of the updated value-based price benchmark for alirocumab, the budget impact may be substantial. Policymakers will need to continue to evaluate strategies to ensure affordable access to alirocumab.

Comment The new evidence from the ODYSSEY Outcomes trial does not alter ICER’s cost-effectiveness assessment for another PCSK9 inhibitor, evolocumab. In September 2017, after assessing new data from the FOURIER outcomes trial, ICER announced that the value-based price benchmark for a year’s treatment with evolocumab would change to a range from approximately $1,700 to $2,200. The primary reason that this price range is lower than the updated range calculated for alirocumab is that, although the FOURIER trial showed that evolocumab combined with statin therapy is effective in reducing the incidence of cardiovascular events such as MI and stroke, the evidence did not demonstrate a statistically-significant reduction in cardiovascular or all-cause mortality, nor a trend toward improved clinical benefit in patients with higher LDL-C levels.