PCSK9 Inhibitors Still Burdened by Poor Cost-effectiveness, Despite FOURIER: New Analyses

Marcia Frellick

August 23, 2017

CHICAGO, IL — Two cost-effectiveness studies of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) add to the list of analyses that conclude that the relatively new injectable, lipid-modifying agents are neither cost-effective nor affordable at the current prices of more than $14,000 a year.

Dr Dhruv S Kazi (Zuckerberg San Francisco General Hospital, CA) and colleagues say the price of the drugs would need to come down by more than two-thirds, to $4536 per year, to meet cost-effectiveness thresholds, according to a research letter published in the August 22/29, 2017 issue of the Journal of the American Medical Association [1].

The other analysis, led by Dr Gregg C Fonarow (University of California, Los Angeles Medical Center) finds the price would need to come down to $9669 a year for US clinical practice to meet the standards for cost-effectiveness. His team's analysis, funded by Amgen, was published online August 23, 2017 in JAMA Cardiology[2].

Both studies were done to consider clinical-outcomes findings released earlier this year from the Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER) trial, which associated the PCSK9 inhibitor evolocumab (Repatha, Amgen) with significantly reduced risk for major adverse cardiovascular events (MACE) when added to statins.

PCSK9 Inhibitors Less Effective at Reducing Mortality

As Kazi told theheart.org | Medscape Cardiology, FOURIER showed that while PCSK9 inhibitors are very effective at reducing LDL cholesterol (by nearly 60%) and fairly good at reducing the risk of heart attacks and strokes, the drugs are not good at reducing mortality and improving survival over the long term.

"We are still trying to understand where that discrepancy comes from," he said. "This is different from statins, which reduce heart attacks and strokes and have a pretty impressive reduction of mortality in the long run."

He emphasized that PCSK9 inhibitors should not be considered an alternative to statins, "not just because they're expensive but because they are less effective than statins for what they do."

Therefore, he says, physicians should push to find a way to help patients better tolerate statins—perhaps at a reduced dosage.

Kazi's update used 2017 prices and simulated the 8.9 million adults who met the FOURIER inclusion criteria. Researchers then looked at whether the FOURIER trial results altered the 2015 findings that concluded PCSK9 inhibitors were not cost-effective.

Researchers found that not only are they still not cost-effective, but even larger price cuts than previously reported would be necessary to hit cost-effectiveness thresholds.

Fonarow et al used different metrics, which explains the difference in price thresholds they identified vs those by Kazi et al. He told theheart.org | Medscape Cardiology that three factors explain the differences.

The first is that "our analysis uses the societal perspective, whereas the Kazi paper uses the insurers' perspective. The difference there is whether indirect costs are considered. In a societal-perspective analysis, they are."

The second is in setting the value-based price. Kazi et al used an incremental cost-effectiveness ratio of $100,000 and Fonarow used $150,000.

The third difference lies in the event rate, which is a debatable figure, Fonarow acknowledges. Kazi's model used a lower event rate than did the Fonarow et al analysis.

"They actually are not that far apart," Fonarow concludes about the studies' main findings.

The advances are clear with PCSK9 inhibitors, he says. They clearly reduce the risk of nonfatal MI and disabling strokes and could mean "hundreds of thousands of fewer major cardiovascular events a year."

He says deep discounting is the best hope for making these drugs available, adding that "there shouldn't be artificial barriers and denials for patients who could benefit."

Poor Return on Investment and Everybody Pays

Dr Daniel B Mark (Duke University Medical Center, Durham, NC) was the lead author on editorials accompanying both studies.

One[3] editorial focuses on the realization that with these drugs "you're putting money into the system and essentially losing value," he told theheart.org | Medscape Cardiology. Fonarow et al put the return on every dollar invested at $0.37. Kazi et al put it even lower, at $0.22, he notes.

The other editorial[4] says that these prices have consequences and everybody pays, which affects the way they are prescribed.

"As physicians, at the very least we have to exercise a certain level of restraint because at the end of the day, although it's easy to forget about it, we are spending people's money and ultimately the extra cost gets distributed to everybody," he says.

In the JAMA editorial, Mark and Dr Kevin A Schulman (Duke University) write that the drugs' prices are forcing payers to severely limit access because the number of people at risk of atherosclerotic complications, including MI and stroke, is huge—nearly 10 million.

"These drugs have achieved the dubious distinction of being the most expensive preventive therapies by far in the history of cardiovascular medicine," they write.

Familiar Struggle

As the editorialists note, this isn't the first time an effective drug has run up against cost barriers. They point to sofosbuvir (Sovaldi, Gilead), a treatment that can wipe out hepatitis C infection at $84,000 for a course of treatment.

The difference is that sofosbuvir is a one-time course of treatment and PCSK9 inhibitors are used long term. But now both drugs call for difficult decisions about who should get them.

"Payers are throwing up as many barriers as they can to keep the stream of costs for this therapy from becoming a torrential river they can't afford," Mark says.

Kazi put the price in perspective: "The median income for a family of four in the US is around $51,000 to $53,000. When you say this one drug costs almost a third of the median income for a family of four in the US, we have a problem."

The study by Kazi et al was supported by the University of California, San Francisco. Kazi reports no relevant financial relationships; disclosures for the coauthors are listed in the paper. The study by Fonarow et al was supported by Amgen. Fonarow reports consulting for Amgen, Janssen, and Novartis; disclosures for the coauthors are listed in the paper. Mark reports grants from Eli Lilly, Gilead, AstraZeneca, Bristol Myers Squibb, Merck, and Oxygen Therapeutics and consulting fees from Medtronic and Janssen outside the submitted work; disclosures for the coeditorialists are listed in the paper. Schulman reports receiving research support from Amylin Pharmaceuticals and Merck; having equity in and serving on the executive committee of Faculty Connection, as a board member of Bivarus, on the board of directors of Cue Biologics (now Grid Therapeutics), as a managing member of the Physician Education Leadership Institute, and being on the scientific advisory board of Cardinal Analytx; having equity in Cancer Consultants; and having served on the board of Anthelio.

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