PCSK9 Inhibitor Prices Should Fall Two-Thirds for Cost-effectiveness: Analysis

Larry Hand

August 16, 2016

SAN FRANCISCO, CA — Two recently approved proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are not cost-effective at 2015 prices for lowering LDL cholesterol in US patients with familial hypercholesterolemia (FH) or atherosclerotic cardiovascular disease (ASCVD), according to a new study[1].

To be cost-effective, prices of the two drugs, injectibles evolocumab (Repatha, Amgen) and alirocumab (Praluent, Sanofi/ Regeneron), would have to drop by more than two-thirds, researchers say.

"We chose scenarios and assumptions that were favorable to these two therapeutics so that we were sure to capture the large health benefits anticipated from their use," senior author Dr Kirsten Bibbins-Domingo (University of California, San Francisco), told heartwire from Medscape by email. "Even under these assumptions, in all of our scenarios, these medications are not cost-effective at current prices."

Bibbins-Domingo and colleagues used the Cardiovascular Disease Policy Model, which is a simulation of coronary heart disease and stroke in US adults 35 and older, in evaluating cost-effectiveness of PCSK9 inhibitors or ezetimibe (Zetia, MSD International) in heterozygous FH or ASCVD. The 2015 annual PCSK9-inhibitor cost of $14,350 was based on mean wholesale acquisition costs of evolocumab and alirocumab.

The results were published online August 16, 2016 in the Journal of the American Medical Association.

The researchers analyzed data for lifetime major adverse cardiovascular events (MACE), incremental cost per quality-adjusted life-year (QALY), and total effect on healthcare spending over 5 years.

They found that adding PCSK9 inhibitors to statins in heterozygous FH patients was estimated to prevent 316,300 MACE at a price tag of $503,000 per QALY gained, compared with adding ezetimibe to statins.

For ASCVD patients, the researchers found that adding PCSK9 inhibitors to statins was estimated to prevent 4.3 million MACE at a cost of $414,000 per QALY, compared with adding ezetimibe to statins.

Initiating statins in high-risk populations for statin-tolerant patients not currently taking statins was estimated to save $12 billion.

For PCSK9 inhibitors to be cost-effective at $100,000 per QALY, the annual drug costs would need to be reduced from $14,350 to $4536 per patient or less, the researchers conclude.

The researchers estimated that use of PCSK9 inhibitors in all eligible patients could reduce cardiovascular care costs by $29 billion over 5 years, but drug costs could increase by $592 billion.

"Much discussion has focused on the high cost of therapeutics, but often new costly drugs are designed to be used in a small population or for a limited duration and thus may be absorbed by a healthcare budget," Bibbins-Domingo said. "These drugs are different because they are designed for lifetime use in a very large patient population. At current prices, use of these two medications in all patients for whom they are indicated would result in a 38% increase in national expenditure on prescription drugs and a 4% percent increase in total healthcare expenditure."

She continued, "Our study does not address whether one should prescribe these medications. The evidence suggests these drugs are highly effective at lowering LDL cholesterol and thus are potentially very important therapeutics for many people. Importantly, the cost of these drugs in many countries in Europe, where they were introduced at the same time as in the US, is much closer to the cost-effective price we identify in our study."

Dr Jennifer G Robinson (University of Iowa, Iowa City), who authored a recent article on nonstatins and PCSK9 inhibitors[2], told heartwire by email that the decision whether to prescribe these drugs "is one factor to consider when determining whether to add an expensive nonstatin. There are some very high-risk patients whose LDL cholesterol remains high who could benefit, such as those with familial hypercholesterolemia who have already developed clinical cardiovascular disease. We don't do cost-effectiveness analyses for other genetic diseases for drugs that could be essentially curative of the disorder."

However, she added, "Companies with new cholesterol-lowering drugs coming down the pipeline would be well advised to price their drugs more reasonably."

Bibbins-Domingo added, "Also important for the decision about prescribing is that nationally one-third of patients with FH or atherosclerotic CVD and elevated LDL are not taking statins, still the first-line medication in these individuals. Getting all of these individuals on statin medications is not only cost-effective, but actually cost saving. PCSK9 inhibitors were approved for those on maximally tolerated statins with LDL not at goal. Nationally we need to do a better job getting these high-risk patients on statins."

The New England States Consortium Systems Organization and the Laura and John Arnold Foundation supported this research. Bibbins-Domingo has no relevant financial relationships. Disclosures for the coauthors are listed in the article.

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