ICER Chief on Bempedoic Acid and Inclisiran: Don’t Repeat the PCSK9 Mistake

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In this new episode of MHE Talks: Improving Patient Access podcast, Steven D. Pearson, M.D., M.Sc., warns that high prices can squander an opportunity to bring innovative medications into clinical use.

ICER came out with a report a month ago on two cholesterol-reducing agents that may compete with the PCSK9 inhibitors, according to Steven D. Pearson, M.D., M.Sc., founder and president of ICER, said in a recent interview with Managed Healthcare Executive.

Pearson warned about repeating the mistakes of the past and those early high-priced, low-uptake years of Praluent and Repatha.

“We all should just be aware that price and access are joined at the hip,” Pearson told MHE. “It did feel that the first few years after the PCSK9 inhibitors came out, there was an opportunity squandered because of all the friction and the difficulty that patients and doctors had. And certainly the companies felt like the uptake of the PCSK9 inhibitors — and their revenues — weren’t good.”

The two drugs assessed in the ICER report are bempedoic acid and inclisiran. Bempedoic is sold as Nexletol and, in combination with ezetimibe, as Nexlizet. The FDA held up approval of inclisiran after it found manufacturing problems at a plant in Italy, where the drug is made. ICER says its cost-effectiveness math shows that a fair annual price for the bempedoic acid/ezetimibe combination would be between $1,600 and $2,600, which would be 36% to 60% less than the current wholesale acquisition. ICER’s cost-effectiveness math for inclisiran, which doesn’t have a price yet because it is not the market, put the price tag between $3,600 and $6,000. Pearson said the PCSK9 inhibitors were a hard lesson learned about the dynamics of pricing and squandering the opportunity to bring innovative drugs into clinical use. “If we can get the prices aligned at the front end, that just gets the ball rolling in the right direction.”

Whether inclisiran will be considered to be in the same class as the PCSK9 inhibitors could be a complicating factor in the drug’s uptake. It has a different mechanism of action but does work in the same biochemical pathway, noted Pearson: “A clinician would tell you that it serves the same purpose.” One possible advantage of inclisiran is that it needs to be administered only twice a year, albeit by a healthcare professional, in contrast with the once- or twice-monthly self-administered injections of Praluent and Repatha. A clinician with experience in underserved communities commented at an ICER meeting that the less frequent dosing, administered in a doctor’s office, would be an advantage for many of the patients he cares for, Pearson said.

If and when someone writes the history of drug pricing in the U.S., the cholesterol-lowering PCSK9 inhibitors are likely to be a paradigmatic chapter. When Repatha (evolocumab) and Praluent (alirocumab) came on the market in 2015, their list prices were more than $14,000 a year. But expectations of wide use and big sales crashed and burned. Payers and, to some extent, physicians bridled at the price of the new drugs, which are administered by self-injection. The Institute for Clinical and Economic Review (ICER), the cost-effectiveness research organization in Boston, had already made a name for itself in the controversy about the pricing of the hepatitis C antivirals. It weighed in with a cost-effectiveness assessment that said the prices of the PCSK9 inhibitors should be slashed by 60% or more.

“I think it actually just affirmed what many payers and others were feeling, which was that this seemed like an expensive drug for the clinical value that it was going to provide for the average patient,” Pearson said.

“What was unique about them (the PCSK9 inhibitors) was that they were a completely new paradigm of care for patients with high cholesterol,” Pearson continued. “There are obviously a lot of patients in the country who had high cholesterol despite using the available pills, so the potential for the budget impact was so high that it caught a lot of people’s attention.”

Starting in 2018, Sanofi and Regeneron, the manufacturers of Praluent, and Amgen, which makes Repatha, started to compete on price, and by 2019, the annual price tags of their PCSK9 inhibitors were below $6,000, still more expensive than the price ranges recommended by ICER (which has revised them since 2015 as new study results have been reported) but still half of the initial price. In a February earnings report, Amgen stated that sales revenue from Repatha increased by 34% in 2020 compared with 2019, with a 67% increase in volume largely responsible for the uptick. At about the same time, Sanofi reported that sales of Praluent increased by 2.3% in 2020.

So arguably a tick in the win column for tying drug prices to cost-effectiveness — and for ICER — right?