Evolocumab ‘Abjectly Fails’ Another Financial Stress Test

The PCSK9 inhibitor evolocumab (Repatha, Amgen) is far too expensive to make economic sense for the healthcare system and private payers, according to the results of yet another cost-effectiveness analysis casting a harsh light on the drug’s price.

At its current list price of $14,300 per year of treatment, evolocumab costs approximately three times too much, and the drug’s price would need to be slashed by at least 62% to meet society’s currently accepted cost-effectiveness thresholds.

As it stands now, the incremental cost-effectiveness ratio (ICER) is $337,729 per quality-adjusted life-year (QALY) gained. If evolocumab were to be priced at $5,459 per year instead, only then would it reach the typically accepted willingness-to-pay threshold of $100,000 per QALY gained, according to researchers.

Speaking with TCTMD, senior investigator Khurram Nasir, MD (Baptist Health South Florida, Coral Gables), said leadership is urgently needed from all the pertinent stakeholders—the American Heart Association, American College of Cardiology, US Food and Drug Administration (FDA), payers, patient advocacy groups, and pharmaceutical companies—to determine how to establish drug prices given the benefits observed in clinical trials.

“It’s a wake-up call for us, and we need a pragmatic solution,” said Nasir. “The therapy works, but it’s a question of whether it’s priced appropriately for its value.”

In the FOURIER trial, adding evolocumab to high-intensity statin therapy in patients with stable atherosclerotic cardiovascular disease reduced the risk of cardiovascular death, MI, stroke, hospitalization for unstable angina, or coronary revascularization—the study’s primary endpoint—by 15% when compared with placebo, an absolute difference of 1.5%. In terms of individuals endpoints, the benefit was driven by a reduction in nonfatal events, with no significant reduction in cardiovascular mortality.

The results of this latest cost-effectiveness analysis, led by Alejandro Arrieta, PhD (Florida International University, Miami), were published October 18, 2017, in JAMA Cardiology.

Not a Hard Line in the Sand

Since the annual price of evolocumab and alirocumab (Praluent, Sanofi/Regeneron), the other FDA approved and similarly priced PCSK9 inhibitor, were listed, there have been more than a few eyebrows raised regarding the high cost of treatment. In addition to this latest cost-effectiveness analysis, two other studies have shown that evolocumab fails to meet the typical threshold used for willingness-to-pay decisions.

“These cost-effectiveness analyses are designed to help [stakeholders] figure it out—the numbers are not lines in the sand,” said Nasir, referring to an objectively-determined value-based price. “It doesn’t mean we won’t pay higher or lower, but clearly at $14,000 it isn’t cost-effective. Period. Now where it is cost-effective, and how much we’re willing to pay as a society, that input needs to come from multiple stakeholders.”

The therapy works, but it’s a question of whether it’s priced appropriately for its value. Khurram Nasir

Andrew Foy, MD (Penn State College of Medicine, Hershey, PA), who was not involved in the study, said he was not surprised by the new findings, particularly given the drug’s controversial high price and the benefit observed in the FOURIER study.

“It’s nice when these cost-effectiveness analyses formally support what a lot of people are thinking,” Foy told TCTMD. “When you look at the primary clinical trial, which a lot of the assumptions underlying this model came from, it was a very small reduction in nonfatal CVD events for a drug that costs over $1,000 per month. It is almost obvious that it’s not going to be cost-effective.”

In addition to the treatment costs imposed on the healthcare system, there are financial burdens for patients, even those with excellent insurance, he added.

“It’s slightly different for patients who are statin intolerant, although even in those patients, the cost of the drug is hard to justify,” said Foy. “For patients who can be optimized on statin therapy, which is relatively inexpensive at this point, to think you’re gaining much benefit by putting them on an extremely expensive drug, I do think physicians need to think about [cost]. For me, evolocumab never really made much sense at this price.”   

To TCTMD, Nasir noted that there have been previous studies and reports highlighting the challenges that many individuals have in accessing PCSK9 inhibitor therapy, even when use is considered appropriate. In discussions about improving access to treatment, though, the biggest impediment is the drug’s high price, which is often ignored.

For their part, Amgen stated evolocumab delivers the greatest value to higher-risk patients, those individuals with established CVD who remain at high risk despite optimal statin therapy. In a statement to TCTMD, they acknowledged that most payers are not paying the full price due to discounts and rebates, making the drug a better value proposition in these high-risk patients.

“Amgen is working with payers to offer value-based pricing through various contracting options for [evolocumab], and we remain committed to working with payers to help them manage their costs if they are prepared to ensure that their appropriate high-risk patients get access to the high-value medicines they need,” they said.

Negative Return on Investment for Payers

In addition to evaluating the cost-effectiveness of evolocumab, the researchers also assessed the return on investment from a private payers’ perspective. In short, covering the annual costs of evolocumab as it is currently priced resulted in a negative return on investment.

For example, for every dollar spent on evolocumab, private insurers lose $1.86. Putting one patient on the PCSK9 inhibitor would result in a net present value loss of $35,907 to the payer. From the private payer perspective, the breakeven price in which the return on investment is zero, evolocumab needs to be priced at $2,381 per year. 

For me, evolocumab never really made much sense at this price. Andrew Foy

“I think cost-effectiveness analyses, especially in the US, should consider the perspective of private insurance payers,” said Nasir. “It’s extremely relevant considering the major [insurance] payers in the US still consist of this market. From their perspective, because they’re not attuned to the lifelong benefits, the price needs to be even lower.”

In an editorial accompanying the study, Robert Bonow, MD, Clyde Yancy, MD (both Northwestern University, Chicago), and Robert Harrington, MD (Stanford University, CA), state that the current pricing of the PCSK9 inhibitors “abjectly fails every analysis of cost-effectiveness, and thus, the available clinical trial data cannot support widespread routine use.”

They point out that in multiple studies, under a variety of scenarios and sensitivity analyses, the data all suggest there is a need to cut the price of the PCSK9 inhibitors by 60% to 70% to achieve the societally acceptable ICER of $100,000 per QALY gained. Moreover, use of evolocumab, albeit over a relatively short time period in FOURIER, did not translate into a reduction in mortality or cardiovascular mortality.

“Until there are more compelling clinical data, ie with a larger benefit, including effects on mortality, the path forward currently requires only one intervention: lower the cost,” according to Bonow, Yancy, and Harrington.

For Foy, while he acknowledges the need for discussions amongst involved stakeholders to establish pricing that reflects a drug’s value, another way to make a statement about the high price of therapy is to simply not prescribe these expensive agents. The drug companies, he said, “will figure it out on their own.”