Inmaculada (Inma) Hernandez, PharmD, PhD, is an assistant professor at the University of Pittsburgh School of Pharmacy. Her research program is built at the intersection of pharmaceutical health services and outcomes research, pharmacoepidemiology, pharmacoeconomics, and pharmaceutical policy. Specifically, she is interested in the real-world use and outcomes of oral anticoagulation therapy in stroke prevention in atrial fibrillation, on the use of large data sets, advanced data mining techniques, and comparative effectiveness research to predict and compare outcomes of medications, and on value-based health insurance and health services delivery.
Outcomes-based pricing arrangements for pharmaceuticals are increasingly popular. In this piece, we discuss the impact of the outcomes-based pricing arrangements proposed by Amgen on the pricing of PCSK9 inhibitor therapy, and we provide recommendations for payers on the design of outcomes-based contracts.
This article has been co-authored by Terri V. Newman, post-graduate fellow in Pharmacoanalytics, Pharmacoeconomics and Outcomes Research, University of Pittsburgh School of Pharmacy; and Natasha Parekh, clinical instructor, University of Pittsburgh School of Medicine, Division of General Internal Medicine; Alvaro San Juan Rodriguez, post-graduate fellow in Pharmacoanalytics, Pharmacoeconomics and Outcomes Research, University of Pittsburgh School of Pharmacy.
In 2015, the FDA approved the PCSK9 inhibitors evolocumab and alirocumab for lowering low-density lipoprotein cholesterol (LDL-C). The approval of these agents was based on clinical trials that found PCSK9 inhibitors reduced LDL-C levels by around 60%. Based on this LDL-C reduction, PCSK9 inhibitors were predicted to reduce the risk of cardiovascular events by around 36% to 39%. As clinicians, patients, and payers waited for the results of 4 large phase 3 trials powered to assess the efficacy of PCSK9 inhibitors in the prevention of cardiovascular events, these predictions generated high expectations for the potential of this therapeutic class in the treatment of atherosclerotic cardiovascular disease. Some even postulated that, despite their current price of $14,000 per year of treatment, PCSK9 inhibitors could dramatically decrease the burden of atherosclerotic cardiovascular disease at a price comparable with other lipid lowering therapies because of the cost savings associated with avoiding downstream cardiovascular events .
The results of the FOURIER trial, the first of 4 large clinical trials conducted to assess the efficacy of PCSK9 inhibitors in the prevention of major cardiovascular events, were published in March 2017. It found that the PCSK9 inhibitor evolocumab reduced the risk of major cardiovascular events, including cardiovascular death, myocardial infarction (MI), stroke, hospitalization for unstable angina, and coronary revascularization, by 15%. Evolocumab was further associated with a 27% reduction in the risk of MI, and a 21% reduction in the risk of stroke. The failure of these results to meet the expectations generated by previous predictions was reflected in media and in the stock market, immediately following their publication. While experts suggested that Amgen would have to reconsider the pricing of evolocumab, Amgen announced its willingness to offer innovative contracts payers to remove access barriers to evolocumab. Specifically, Amgen offered to refund payers the cost of evolocumab for patients who have a MI or a stroke while using the drug.
In a recent research letter in JAMA Internal Medicine, Hernandez simulated the impact that these contracts would have on the price of evolocumab to demonstrate that they would barely decrease the annual price of evolocumab by 2% to 3%. These refunds would be considerably lower than current discounts offered for evolocumab, which according to Amgen, average between 30% and 35%. Even after the application of both current discounts and outcomes based refunds, the annual price of evolocumab therapy would be around $9000, which is 2 to 3 times the price at which evolocumab would be cost effective.
It is important to consider the clinical value and cost-effectiveness of these drugs in the context of the current LDL-C treatment guidelines. A recent update to the American College of Cardiology Expert Decision Consensus Pathway made some key changes on the role of non-statin therapies in the management of atherosclerotic cardiovascular disease. One particular change involves the expanded consideration given to PCSK9 inhibitors in the secondary prevention of patients with clinical disease and comorbidities already on a statin. Prior to the guideline update, if this treatment group required the addition of a non-statin therapy for further LDL-C lowering, ezetimibe would be preferred. However, ezetimibe and PCSK9 inhibitors are given equal consideration in the new update. As clinicians and payers await publication of the results of the ODYSSEY trial scheduled for later this year, the debate on the place of PCSK9 inhibitors in clinical practice will likely continue. It will be particularly important to consider whether clinical guidelines should account for the price and cost-effectiveness of the agents under evaluation when providing recommendations.
In addition to the important implications on the place in therapy of PCSK9 inhibitors, this research letter raises 6 important points for payers to consider while designing outcomes-based contracts:
In summary, in order for outcomes-based pricing agreements to translate into an increased value in pharmaceutical use and spending, their formulation should be carefully designed to account for the peculiarities of the management of pharmaceutical benefits, as well as for the cost-effectiveness of the therapy under evaluation.