More Bang, Less Buck: Cost-Effectiveness Analysis Says Price of PCSK9 Inhibitors Needs to Drop by Two-Thirds

Price has long been the elephant in the room with PCSK9 inhibitors, and new cost-effectiveness data are only fueling the fire of critics who claim the cost of the novel injectable cholesterol-lowering medications is not sensible compared with cheaper alternatives.

It has been about 1 year since the US Food and Drug Administration (FDA) approved both alirocumab (Praluent; Sanofi/Regeneron) and evolocumab (Repatha; Amgen)—monoclonal antibodies delivered via subcutaneous injection—for particular types of patients who require LDL lowering.

The indications for the agents are similar, with alirocumab approved for patients who fail to achieve sufficient LDL cholesterol lowering through diet and maximally-tolerated statin therapy, including those with heterozygous or homozygous familial hypercholesterolemia (FH). The FDA approved evolocumab for use in addition to diet and maximally tolerated statin therapy in adults with heterozygous and homozygous FH or clinical evidence of atherosclerotic cardiovascular disease who require further LDL-cholesterol lowering.

Yet these drugs haven’t come to dominate the marketplace, mostly due to the fact that they each cost more than $14,000 per year per patient and statins are priced generically at a fraction of that, according to Kevin Schulman, MD (Duke Clinical Research Institute, Durham, NC), who was not involved in the study. “I think overall the idea of taking a chronic therapy for thousands of dollars more, probably tens of thousands more, than oral therapy is very hard to justify,” he told TCTMD.

Moreover, “the science is still out. We’ve got these two clinical trials that show a benefit in terms of cholesterol reduction, which is great,” Schulman said. But even if PCSK9 inhibitors reduced all cardiovascular events, they are still “too expensive,” he stressed. “We’re paying more to treat the disease with these drugs than we are without the drugs. They are not saving us any money.”

Cost-effectiveness data published in the August 16, 2016, issue of the Journal of the American Medical Association indicate that the mean annual price of PCSK9 inhibitors in 2015 needs to be reduced by about two-thirds—from more than $14,000 to $4,536—to meet standard acceptable thresholds ($100,000 per quality-adjusted life-year [QALY]).

Dhruv S. Kazi, MD (University of California, San Francisco), and colleagues used the Cardiovascular Disease Policy model to calculate that adding these drugs, instead of ezetimibe, to statins in patients with heterozygous FH and atherosclerotic cardiovascular disease results in the prevention of 316,300 and 4.3 million MACE, respectively. This equates to respective costs of $503,000 and $414,000 per QALY in these populations.

Additionally, though PCSK9 inhibitors were predicted to reduce cardiovascular care costs by $29 billion over 5 years if used in all eligible patients, their model showed drug expenditures increasing by about $592 billion, which represents a 38% increase over 2015 drug costs. In contrast, they estimated that oral statins would save $12 billion if given to all high-risk populations of statin-tolerant patients who aren’t currently taking them.

“Our concern is that PCSK9 inhibitor therapy is relevant to a very large section of the US population and is meant to be taken as preventive therapy for life. So the drug expenses we’re talking about now are on a completely different scale,” said Kazi in an audio interview published to the JAMA website. “Our hope is that our findings will prompt a national debate about how we price drugs in the United States.”

Are PCSK9s the New Sovaldi?

“What this article points out is that it’s hard to understand the value of these products,” Schulman said. Although he is “100% sure” that the manufacturers reviewed similar cost-effectiveness analyses before setting their prices, “to my knowledge,” he said, “they haven’t come out to justify the price that they set by the value that they are creating for individuals.”

But Schulman noted that even $4,500 is “actually a little too generous” a price for PCSK9 inhibitors given that millions of people could potentially take one of the drugs. “At $50-$100,000 per QALY, your premium is going to go up,” he said. “Most of us are not very happy with healthcare costs today. You could actually price this so that your premium would not go up at all.”

Although he admitted to not having seen the current sales figures, Schulman said he imagines they “are not as robust as [the drugs’ manufacturers] would have hoped.”

He guessed that for the near future, use of PCSK9 inhibitors will “stay restricted” unless the price drops. Schulman said he would not even consider prescribing these drugs to the patients cited in the study, instead only opting for them in the case of a “very rare genetic mutation,” and encouraged other physicians to “stand firm on this one. There’s no way to finance this product at this price for broad segments of the population.”

Given the apparent disconnect between pharmaceutical companies and cost-effectiveness, Schulman said consumers and tax payers will have to decide when enough is enough. He likened this situation to what happened last year with the hepatitis C drug Sovaldi (Gilead), which was priced at $84,000. “You can look at the profits Gilead made last year off Sovaldi and their margins got up to about 50%, so basically your taxes went to those profits,” he said.

But the healthcare community has learned from the past, according to Schulman. “Because of that, this one didn't just slide through,” he said. “This one met a lot of resistance because people were upset with that one. People were ready to deal with the pricing issues.”

Related Stories:

• PCSK9 Inhibitors: Good Early Responses With Pricey Drugs, but Doctors Still Waiting on Real Data
• Optimal Risk Factor Control Translates Into Less Expenditure on Healthcare, Use of Resources
• Statins Lower but Don’t Erase the Excess Risk of Coronary Disease and Death in Familial Hypercholesterolemia