How ICER and cost-effective analyses influence the pricing of drugs such as icosapent ethyl.
Deepak L. Bhatt, MD, MPH: I can talk now a little bit about ICER. Not the ICER in a way that Dr Bress was referring to, but rather, the Institute for Clinical and Economic Review, which also has the acronym ICER. The folks from ICER recently put out a report on cost-effectiveness of additive cardiovascular disease therapies. Particularly, they cover 2 relatively recent advances: rivaroxaban, which, at the so-called vascular dose, was found to be highly effective in the COMPASS trial, and icosapent ethyl due to the REDUCE-IT trial. Maybe I can turn to Dr Bress to hear his thoughts on the report’s findings. Did you agree with it? They deemed both of those drugs cost-effective. And then, do you have further thoughts on whether we should implement those findings?
Adam Bress, PharmD, MS: Absolutely. The ICER group is a high-quality group, and I agree with their findings, in general. To review their findings, the ICER report, and I’m going to focus on icosapent ethyl here, was published last October. The report used a standard literature-based Markov model, which means they used data from published sources and didn’t have access to individual participant level data from any of the trials to estimate the cost-effectiveness of icosapent ethyl versus placebo in REDUCE-IT eligible patients over a lifetime from a payer or health sector perspective.
The model applied treatment effects from REDUCE-IT and health care and medication cost data from national and commonly used sources. The top-line result, as Dr Bhatt mentioned, was assuming an icosapent ethyl cost of about $133 a month. This reflects a net pricing cost or a reduced cost, which is an estimate of what they believe pharmacies and health systems are paying for the product. The model predicted that icosapent ethyl compared to standard care cost approximately $18,000 per QALY [quality-adjusted life years] gained.
What this means is that use of icosapent ethyl in a REDUCE-IT eligible population was cost-effective and well below common US willingness-to-pay thresholds, and would be considered to be of high value according to the American Heart Association and American College of Cardiology. And therefore, the higher medication costs of icosapent ethyl were balanced by health gains from prevented cardiovascular disease events.
Deepak L. Bhatt, MD, MPH: Yes, I think that’s a nice way of explaining it to the audience. Increasingly, I believe physicians will have to keep on top of these sorts of evaluations of cost-effectiveness. No question about that.
Can I also just ask you, Dr Bress, to talk a little about some of the REDUCE-IT cost-effectiveness analyses? You and your colleagues have played a pivotal role in performing those, but maybe for the audience you can give them a recap of what was presented by Bill Weintraub, MD, at the American Heart Association meeting as a late-breaking clinical trial in 2019.
Adam Bress, PharmD, MS: Sure, Dr Bhatt. It’s been a pleasure for me to connect with you and Dr Weintraub on this analysis. What was presented at the American Heart Association sessions last November was a preliminary report of a project that, as opposed to the ICER report, is using actual patient level data from the REDUCE-IT trial. We applied a combination alongside the trial and simulation-based cost-effectiveness approaches to estimate the lifetime cost-effectiveness of icosapent ethyl versus placebo in REDUCE-IT eligible patients.
The patient level component is important because it allows for us to, in a more granular way, fully capture the effects of icosapent ethyl during the trial on critical costly events like revascularizations, as mentioned before by Dr Budoff. The top-line results from this analysis were that icosapent ethyl at a discounted price of $125 per month, which is very similar to the cost input used in the ICER report, was cost-saving in almost all scenarios, and regardless if treatment effects persisted or decayed in the post-trial period. And what this means is that icosapent ethyl offers better health at a lower cost overall when used in the REDUCE-IT eligible population over a lifetime. This is due to the cost savings from averted events completely offsetting the cost of the medication.
Deepak L. Bhatt, MD, MPH: That’s a very nice summary. How would you say this compares to the cost-effectiveness analyses for the PCSK9 [proprotein convertase subtilisin/kexin type 9] inhibitors?
Adam Bress, PharmD, MS: That’s an important comparison. I might start with the fact that cost savings in cardiovascular disease prevention, whether primary or secondary, is very rare. The only 2 interventions that I’m aware of in cardiovascular disease research that are cost-saving are treating hypertension compared to not treating it among high-risk people, and low-cost generic statins for secondary prevention.
Among those with a pooled cohort ASCVD [atherosclerotic cardiovascular disease] 10-year risk of greater than 7.5, statins for primary prevention cost about $40,000 per QALY, to give you some context. And in terms of the PCSK9 inhibitor analyses, I’ll refer to the ODYSSEY OUTCOMES trial that you led, so please correct me if I’m wrong on anything I mention. But that trial found that among patients with a recent acute coronary syndrome, and with an LDL above 70 mg/dL and on good doses of atorvastatin or rosuvastatin, alirocumab cost about $100,000 per QALY, overall. But among those with an LDL cholesterol at baseline above 100 mg/dL, alirocumab had much higher value. I believe with the ICER, it was around $40,000 per QALY. So when comparing icosapent ethyl, a branded medication, to another branded medication, a PCSK9 inhibitor, the value assessment looks very different. Icosapent ethyl looks much more favorable, from a value standpoint, from the cost-effectiveness analysis we have right now.