PCSK9 inhibitor alirocumab not cost-effective despite price cut

The recent price cuts of the PCSK9 inhibitor alirocumab (Praluent) aren’t enough to make the cholesterol-lowering drug cost-effective compared to ezetimibe, according to an analysis published in the Jan. 1 issue of the Annals of Internal Medicine.

Researchers led by Dhruv S. Kazi, MD, MSc, with Beth Israel Deaconess Medical Center in Boston, used data from the ODYSSEY Outcomes trial to assess the cost-effectiveness of alirocumab added to statin therapy in a population with a recent acute coronary syndrome and baseline LDL cholesterol of 70 mg/dL or higher. In that trial, use of the PCSK9 inhibitor was associated with a 15 percent reduction in all-cause mortality and an equivalent reduction in a composite of myocardial infarction, ischemic stroke, hospitalization for unstable angina and coronary heart disease death over a median follow-up of 2.8 years.

Despite those improvements in clinical outcomes, Kazi et al. calculated alirocumab would need to be slashed to $1,974 annually to be cost-effective at $100,000 per quality-adjusted life year (QALY) relative to ezetimibe—another adjunct to statin therapy that can further lower LDL cholesterol. Ezetimibe, which is far cheaper than both commercially available PCSK9 inhibitors, has also been linked to reductions in major adverse cardiovascular events (MACE) but not to the same extent as alirocumab or evolocumab.

The incremental cost-effectiveness of alirocumab looks even worse when compared to the wholesale price of generic ezetimibe ($304.38), Kazi et al. reported.

“For alirocumab to be cost-effective relative to generic ezetimibe, its annual price would have to be reduced to $874, which would be unprecedented for biologic therapies in the U.S. market,” the authors wrote.

The annual price of alirocumab was around $14,600 when this analysis was performed, but was later dropped to between $4,500 and $8,000 per year based on an agreement between manufacturers Regeneron and Sanofi and the pharmacy benefit manager Express Scripts. With that deal, Regeneron and Sanofi agreed to provide a larger rebate to Express Scripts in exchange for simpler preauthorization forms and alirocumab being the only PCSK9 inhibitor being offered in Express Scripts’ largest formulary plan, which covers 25 million members.

But even with that nearly 70 percent reduction in list price, the drug wouldn’t be cost-effective at a willingness-to-pay threshold of $100,000 per QALY for even the most high-risk patients in Kazi et al.’s model.

The researchers applied reductions in MACE seen in ODYSSEY and a randomized trial of ezetimibe to a model population of 215,000 U.S. adults. The hypothetical patients had all experienced a first MI in the previous 12 months and had a baseline LDL cholesterol above 70 mg/dL despite taking statins. Kazi and colleagues then calculated costs from a health system perspective while considering lifetime event rates for each patient out to 95 years of age or death.

Assuming a 15 percent reduction in MACE—as seen in the ODYSSEY trial—alirocumab still wasn’t cost-effective versus ezetimibe among patients with a baseline MACE rate of 7.2 events per 100 patient-years. In this high-risk scenario, the yearly price of alirocumab would need to be reduced to around $2,000 to meet the common willingness-to-pay threshold of $100,000 per QALY relative to ezetimibe.

These findings appear to support the recommendations in the 2018 U.S. cholesterol guidelines, which suggest ezetimibe as a second-line approach when statins alone aren’t sufficiently reducing LDL cholesterol. PCSK9 inhibitor injections are recommended only as a third-line approach if statins plus ezetimibe fail to produce the desired results.

“Targeting higher-risk groups would reduce the number of patients eligible for therapy and ameliorate the total budget impact of adopting this novel therapy, but unless this focus on a higher-risk population is complemented by a substantial reduction in drug price, achieving cost-effectiveness at conventional willingness-to-pay thresholds will not be possible,” Kazi et al. wrote of alirocumab.

The authors performed a prior cost-effectiveness analysis of PCSK9 inhibitors that didn’t look quite as grim, but they said since then the cost of brand-name ezetimibe has dropped and generic formulations have become available.

“Because of our experience, we encourage other members of the academic community to become involved in evaluating the cost-effectiveness of new therapies in a timely manner,” they wrote. “We believe that this involvement may positively influence the pricing and adoption of interventions that are useful to patients, just as important clinical trials have the potential to influence clinical practice.”