A historical overview of how PCSK9 inhibitors have been priced to treat dyslipidemia, and payer reactions to decisions for utilization.
Deepak L. Bhatt, MD, MPH: Perhaps I’ll turn to Dr Bress. We just heard how great the PCSK9 inhibitors are from Dr Ann Marie Navar and Dr Matthew Budoff. The adverse effects are really rather minimal. But cost has, of course, been the elephant in the room. If it weren’t for cost, the drugs would be used more. How do you factor that in, or how should we factor that in?
Adam Bress, PharmD, MS: Thanks, Dr Bhatt. That’s such an important point. Regarding the historical context of the PCSK9 inhibitors, the first 1 was approved in July 2015 at an annual wholesale cost of about $15,000 per year. Since then, because of low uptake and cost-effectiveness analyses that showed that the value of PCSK9 inhibitors was much lower than what we would commonly expect for high-value therapies at that price point. As a result, in 2018 the 2 manufacturers of the PCSK9 inhibitors reduced the prices by 60%, which was a historic reduction—down to about $5000 per year. Even at those prices in a general secondary-prevention population—and we’ll talk about this a little later—PCSK9 inhibitors are of much better value, particularly among those with elevated LDL [low-density lipoprotein] cholesterol levels above 100 mg/dL.
Quite frankly, Dr Bhatt, the data from population-based samples indicate that the uptake of PCSK9 inhibitors thus far is very low. Data out of the PCORnet registry shows that less than 1% of patients with atherosclerotic cardiovascular disease are using these therapies. Dr Navar has led several analyses showing abandonment rates and co-pays as barriers to patients who have been prescribed these therapies. Rates of primary nonadherence are also high. So in summary, use and uptake of these agents is very low.
Deepak L. Bhatt, MD, MPH: Yeah, it’s kind of a shame because you go through the whole process of clinical trial discovery, the work that goes into that by the investigators, and of course the patients themselves contributing as research participants. Then at the end of all that, you have positive trials that end up having much less impact on clinical practice than would have otherwise been anticipated.
But I think it was a strategic wonder, and I did mention that to people I knew who were working on those programs from the company side in both cases. You know, the price point of $15,000 is a killer, and it tainted the whole class. The price came down, but by that point a lot of physicians had tuned out and practice patterns were entrenched. It was, I think, a bit of a misstep.
Adam Bress, PharmD, MS: Yeah. One point to add is that early on the research led by Dr Navar really indicated that approval rates were low, which was a barrier to patients getting the treatment. Some newer data, again from Dr Navar, that surveyed patients taking PCSK9 inhibitors found that out-of-pocket cost directly to the patient, even if they were approved by their insurer, was the No. 1 barrier to using PCSK9 inhibitors.
Deepak L. Bhatt, MD, MPH: Yeah, a great point and great research as well by Dr Navar. Very useful, practical data.
Let’s turn to Dr Cannon. What do you think of these issues, and how do you deal with them? If PCSK9 inhibitors were $1 a day, all our patients with atherosclerosis—maybe not all, but a lot of them—would be on them. But that’s not the case. That’s not going to be the case anytime soon. There are already other PCSK9 inhibitors that are being developed. They may come in at lower price points, but it’s still unlikely the price will drop dramatically. For right now, how should we, as a health care system, deal with this?
Eric Cannon, PharmD, FAMCP: You bring up a great point. You’ve hit on some of the blunders that occurred early on in the launch of these products. If we look at the high cost they came out at—and Dr Bress did a good job pointing out that the manufacturers relaunched these products at a lower list price in 2018—one of the things, and it points to many flaws in how we provide pharmacy benefits for the population, is we’ve still got many organizations across the country that because of contracting strategies and different things have continued to maintain utilization of those higher-list-priced products. So the manufacturers lowered the list price but left the higher-list-price products available in the market.
For us as a health system, we’ve really focused on preferring products that have a lower list price. Then we’re going to direct them to a single specialty pharmacy. As part of that, it’s really understanding their economics, understanding their benefits. How do we make sure we’ve taken advantage of co-pay assistance and other things that are available in the market? Because the reality is, if we couple co-pay assistance with the patient’s benefits, we can literally provide these products at almost a $0 cost impact to the patient. So it’s a coordinated effort to make sure we get to those patients who are appropriate for the therapy. But once we get to them, we can certainly make sure they get access to the products at almost no cost.
Deepak L. Bhatt, MD, MPH: Yeah, those are really key points, and this is a great example of wonderful science bench to bedside. But then there is literally the issue in implementation science. Dr Navar, I know you and your colleagues are thinking a lot about these issues. If we don’t get the implementation science right, all these great scientific advances—basic research, clinical trial research—end up having much less impact than they otherwise would have.