Could Canada afford PCSK9 inhibitors for all its eligible patients?

A clinical and economic analysis of PCSK9 inhibitors in Canadian patients with atherosclerotic cardiovascular disease (ASCVD) is solidifying physician concerns that the lipid-lowering drugs might be too inaccessible—or too pricey—to benefit the average heart patient.

The CANHEART study, published Nov. 5 in the Journal of the American Heart Association, considered all ASCVD patients eligible for treatment with a PCSK9 inhibitor in Ontario in 2011. According to first author Dennis T. Ko, MD, MSc, the project sought to evaluate the clinical and fiscal feasibility of adopting PCSK9s in a large healthcare system.

“Eligibility and event rates associated with PCSK9 inhibitors have largely been derived from a selected sample or from simulation models, and none has access to real-world data from the entire healthcare system,” Ko and colleagues with the Institute for Clinical Evaluative Sciences wrote. “Real-world data are important because they can provide accurate projections on the baseline rate of the general population, which would allow estimation of the avoidable number of events and the subsequent budget impact associated with widespread therapy adoption.”

The 2017 FOURIER trial served as a jumping-off point for Ko and his coauthors, who assessed eligibility for treatment with PCSK9 inhibitors based on a pared-down version of the FOURIER inclusion criteria. Of the 2.4 million people living in Ontario, the researchers said 5.3 percent had a history of ASCVD.

Again relying on FOURIER parameters, Ko et al. determined about one in two CVD patients in Ontario would be eligible for treatment with PCSK9 inhibitors.

The study found 2.7 percent of the general Canadian population and 51.9 percent of ASCVD sufferers were eligible for PCSK9 inhibitors. According to Ko and colleagues' calculations, if all eligible ASCVD patients took the drugs, primary event rates would fall by 1.8 percent after three years—but that news isn’t all positive. The $44 million cost reduction associated with the cutback in CVD events would be more than offset by the $1.5 billion it would take to adopt PCSK9s on such a large scale.

In a related JAHA editorial, Yale School of Medicine’s Khurram Nasir, MD, MPH, MSc, said studies like Ko et al.’s have shed light on the “sobering” reality that PCSK9 therapy, while effective, isn’t affordable for most CVD patients.

“In this regard, last year was pretty hot for PCSK9 inhibitors,” he wrote. “One thing is clear, irrespective of how we slice or dice the cost/benefit pie, we are likely going to reach the same conclusions: current PCSK9 inhibitor prices are impractical.”

Nasir said Ko and colleagues’ study neglected to consider the impact other, cheaper lipid-lowering medications will have on the market in the future, and didn’t take into account the numbers of CVD patients who neglect to take their statins, modifying their risk for cardiovascular events in ways the researchers didn’t account for.

In a budget impact analysis, Ko and his team estimated that it would cost more than $500 million per year to adopt PCSK9s in Ontario, where the population is 13.6 million. The researchers said that would increase the province’s total medication budget by 4.1 percent, but Nasir isn’t convinced.

He said that, based on the study’s limitations, “it is unlikely that even with liberal assumptions we will ever observe close to a 50 percent PCSK9 inhibitor adoption among eligible patients in real-world situations.” He predicts something more in the $125 million range—a quarter of Ko et al.’s projection—but he doesn’t believe his estimate would be affordable, either. Instead, he suggested turning to patients themselves for feedback.

“Rather than making our own assumptions on value, we need the public to drive the dialogue about the economic value on preventing CVD while balancing the deliberations on opportunity costs at the same time,” Nasir wrote. “If we truly believe that our joint interest centers around patient-centric care, then let us allow their input and understanding to drive consensus on these critical issues.”

He said national guidelines and medical organizations should step up to place a greater emphasis on value-based care and affordable practices. It’s also important, he said, to remember that while FOURIER results were promising, their outcomes “are not miraculous,” and the gains associated with PCSK9 inhibitors shift depending on the stakeholders involved.

“Ko et al. deserve our deepest appreciation for providing insights on existing gaps between the price and value derived from PCSK9 inhibitors,” Nasir wrote. “If these studies can successfully facilitate conversations among stakeholders to agree on the just price for 1-2 percent absolute CVD risk reduction, no less, no more, I am confident that the cost of PCSK9 inhibitors will no longer be the top story in 2019.”

Ko and colleagues’ research was published shortly after biotech company Amgen cut the list price of its PCSK9 inhibitor evolocumab (Repatha) from $14,000 to $5,850. Another deal between Regeneron and Sanofi and pharmacy benefit manager Express Scripts slashed the price of alirocumab (Praluent) from $14,600 a year to between $4,500 and $8,000. It’s unclear how those price cuts will affect PCSK9 policy moving forward.