— The evidence suggests that inclisiran can substantially lower LDL-C with limited safety concerns, and with a less frequent regimen that may enhance therapy adherence; ICER recommends an annual health-benefit price benchmark range of $3,600-$6,000

— Bempedoic acid provides a new oral treatment option that may be helpful particularly for patients who are not able to take statins; however, a discount of at least 36% discount off its list price would be needed to reach the top end of ICER’s benchmark range of $1,600-$2,600 per year

— At February 5 virtual meeting, the Midwest Comparative Effectiveness Public Advisory Committee will review the evidence, hear further testimony from stakeholders, and deliberate over these treatments’ comparative clinical effectiveness, other potential benefits, and long-term value for money

BOSTON, January 22, 2021 – The Institute for Clinical and Economic Review (ICER) today released an Evidence Report assessing the comparative clinical effectiveness and value of inclisiran (Novartis), bempedoic acid (Nexletol®, Esperion Therapeutics), and bempedoic acid/ezetimibe (Nexlizet™, Esperion Therapeutics) for treating heterozygous familial hypercholesterolemia (HeFH) and for secondary prevention of atherosclerotic cardiovascular disease (ASCVD).

“While generic statins continue to serve as effective and affordable medicines for the great majority of people with high LDL cholesterol, both inclisiran and bempedoic acid are likely to be important new treatment options for patients who are unable to lower their cholesterol levels with maximally tolerated statin use,” said Steven D. Pearson, MD, MSc, ICER’s President. “Inclisiran’s ability to lower LDL-C appears similar to that of the PCSK9 inhibitors, but it has not yet completed the FDA approval process, and clinical trials are still ongoing to evaluate the extent to which inclisiran’s effect on cholesterol translate through into lowered rates of heart attacks, strokes, and overall mortality. Bempedoic acid also lowers LDL-C, but to a lesser extent, and results of trials on its longer-term clinical outcomes are still pending. The role in therapy of both drugs will be hotly debated given that inclisiran offers twice-annual dosing that might improve access and help patients sustain their treatment, whereas bempedoic acid, as an oral treatment option, might gain favor as an option for patients who cannot take statins. As always, we look to see whether the price aligns well with the estimated long-term benefits for patients. Inclisiran’s price is not yet known, but our analysis suggests that the current list price for bempedoic acid would need a fairly sizeable discount in order to meet a fair pricing threshold. It is too soon to know whether its rebated price in the commercial market will match this target.”

This Evidence Report will be reviewed at a virtual public meeting of the Midwest Comparative Effectiveness Public Advisory Council (Midwest CEPAC) on February 5, 2021. The Midwest CEPAC is one of ICER’s three independent evidence appraisal committees comprising medical evidence experts, practicing clinicians, methodologists, and leaders in patient engagement and advocacy.

A draft version of this report was previously open for a four-week public comment period. The updated Evidence Report and voting questions reflect changes made based on comments received from patient groups, clinicians, drug manufacturers, and other stakeholders. Detailed responses to public comments can be found here.

Key Clinical Findings

The data suggest that, compared to placebo, inclisiran substantially lowers LDL-C with no safety concerns. Reductions in LDL-C levels do not always translate to a reduction in heart attacks, strokes, or death; however, inclisiran’s mechanism of action is linked closely to that of the PCSK9 inhibitors, which have demonstrated longer-term positive outcomes — including a mortality benefit. ICER determined that this evidence provides high certainty that inclisiran delivers at least a small net health benefit, with the possibility of a substantial benefit (“B+”).

The evidence suggests that bempedoic acid is at least comparable, with the potential of a small net health benefit, when compared to placebo (“C+”). This rating, which also applies to bempedoic acid/ezetimibe versus ezetimibe alone, is attributed to the treatment’s modest ability to lower LDL-C levels, its safety concerns, and the pending results of ongoing studies. Bempedoic acid may provide an even larger reduction in LDL-C levels among the statin-intolerant sub-population.

Key Cost-Effectiveness Findings

While inclisiran’s price is not yet known, ICER’s recommended health-benefit price benchmark (HBPB) range for inclisiran for the broad population of likely eligible patients is between $3,600-$6,000 per year. For bempedoic acid/ezetimibe, ICER’s recommended HBPB range is approximately $1,600-$2,600 per year, a price that would require a 36-60% discount off the treatment’s current wholesale acquisition cost (WAC).

Importantly, the cost-effectiveness for both agents would be improved if they were used exclusively for higher risk subgroups, such as those individuals with established ASCVD who are either statin-intolerant or who have HeFH.

The HBPB is a price range suggesting the highest US price a manufacturer should charge for a treatment, based on the amount of improvement in overall health patients receive from that treatment, when a higher price would cause disproportionately greater losses in health among other patients in the health system due to rising overall costs of health care and health insurance. In short, it is the top price range at which a health system can reward innovation and better health for patients without doing more harm than good.

About ICER

The Institute for Clinical and Economic Review (ICER) is an independent non-profit research institute that produces reports analyzing the evidence on the effectiveness and value of drugs and other medical services. ICER’s reports include evidence-based calculations of prices for new drugs that accurately reflect the degree of improvement expected in long-term patient outcomes, while also highlighting price levels that might contribute to unaffordable short-term cost growth for the overall health care system.

ICER’s reports incorporate extensive input from all stakeholders and are the subject of public hearings through three core programs: the California Technology Assessment Forum (CTAF), the Midwest Comparative Effectiveness Public Advisory Council (Midwest CEPAC), and the New England Comparative Effectiveness Public Advisory Council (New England CEPAC). These independent panels review ICER’s reports at public meetings to deliberate on the evidence and develop recommendations for how patients, clinicians, insurers, and policymakers can improve the quality and value of health care. For more information about ICER, please visit ICER’s website.