— For bempedoic acid, independent appraisal committee votes that the evidence is not adequate to demonstrate a net health benefit over usual care for the entire population of eligible patients, but is adequate when focusing on patients unable to take statins and patients with heterozygous familial hypercholesterolemia (HeFH); at current pricing the committee judged the long-term value for money as low to intermediate, with a 36% discount needed to reach ICER’s health-benefit price benchmark for the entire patient population —

— For inclisiran, by a unanimous vote the evidence was judged adequate to demonstrate a net health benefit over usual care alone.  If priced at parity with current pricing for PCSK9 inhibitors, the committee voted that inclisiran would represent a low-to-intermediate long-term value for money; ICER’s recommended net price benchmark range for inclisiran is $3,600-$6,000 per year —

— At the policy roundtable, experts emphasize the need to align pricing and access in order to reduce health inequities, streamline access to new therapies for patients in high-risk populations, and promote broader use of statins and ezetimibe as effective, low-cost treatment options —

BOSTON, March 2, 2021 – The Institute for Clinical and Economic Review (ICER) today released a Final Evidence Report  and Report-at-a-Glance assessing the comparative clinical effectiveness and value of inclisiran (Leqvio®, 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).

“The innovation in recent years that has produced new treatment options for patients with high cholesterol is impressive.  The unmet need and the potential impact on population health is substantial.  And yet, with the large number of patients who could benefit from these treatments, the potential price tag is impressive as well,” said Steven D. Pearson, MD, MSc, ICER’s President.  “That’s why it’s so important to provide a choice among multiple treatment options for patients with diverse needs, and to ensure that patients and the health system can afford these treatments.  We saw this opportunity squandered in the early years of PCSK9 inhibitors.  The only way we get this right for patients moving forward is to price new treatments to their demonstrated clinical value, and link that to responsible insurance coverage criteria that are based on evidence and informed by input from clinical experts and patients.” 

“Unfortunately, as the independent appraisal committee confirmed, current pricing for bempedoic acid is too high to get the ball rolling in the right direction.  We’ll have to wait to see what the price will be for inclisiran, but it would be a real loss for patients if at the outset of another round of new innovation drug makers set prices that send us right back into another grinding number of years in which access is limited while drug makers and insurers wrestle over what is viewed as an unreasonable price.  Patients deserve better.”

ICER’s report on these therapies was reviewed at the February 2021 public meeting of the Midwest Comparative Effectiveness Public Advisory Council (Midwest CEPAC), one of ICER’s three independent evidence appraisal committees.

Voting on Clinical Effectiveness and Contextual Considerations

During the public meeting, the Midwest CEPAC panelists evaluated the clinical evidence for these treatments for all adult patients with established ASCVD and/or HeFH who have elevated LDL-C levels despite treatment with maximally tolerated oral lipid-lowering therapy.

A majority of panelists (12-2) found that the evidence is adequate to demonstrate that bempedoic acid provides a net health benefit for patients who are either statin-intolerant or who have HeFH, but not adequate (11-3) to demonstrate a net health benefit for the broader population of individuals with high cholesterol.

All panelists (14-0) also found that the evidence is adequate to demonstrate a net health benefit of adding inclisiran to usual care.

During their deliberations, panel members also weighted these treatments’ other potential benefits, disadvantages, and contextual considerations. A majority affirmed that when making judgements on overall long-term value for money, policymakers should give high priority to the magnitude of the lifetime impact on individual patients of the condition being treated.

Voting on Long-Term Value for Money

After reviewing the clinical evidence and considering the treatments’ other potential benefits, disadvantages, and contextual considerations, the Midwest CEPAC evaluated the long-term value for these treatments when used in three different patient populations:

  • Population 1: All adult patients with established ASCVD and/or HeFH who have elevated LDL-C levels despite treatment with maximally tolerated statin therapy
  • Population 2: All adult patients with established ASCVD – with or without HeFH – who have elevated LDL-C levels and have statin-associated side effects (“statin intolerant”)
  • Population 3: All adult patients with HeFH who have elevated LDL-C levels despite treatment with maximally tolerated statin therapy

For all population 1, a majority of CEPAC panelists found at the current pricing, adding bempedoic acid/ezetimibe to usual care represents a low long-term value for money. For populations 2 and 3, a majority of panelists found that adding bempedoic acid/ezetimibe to usual care represents an intermediate long-term value for money. ICER’s recommended health-benefit price benchmark (HBPB) for bempedoic acid/ezetimibe is approximately $1,600-$2,600 per year, a range that would require a 36-60% discount off the treatment’s current wholesale acquisition cost (WAC).

For population 1, a majority of CEPAC panelists found that, if priced in line with the current list prices of the PCSK9 inhibitors, inclisiran to usual care represented a low long-term value for money. For populations 2 and 3, adding inclisiran to usual care represented an intermediate long-term value for money. While inclisiran’s price is not yet known, ICER’s HBPB range for inclisiran for the broad population of likely eligible patients is between $3,600-$6,000 per year.

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.

Key Policy Recommendations  

Following the voting session, a policy roundtable of experts — including clinical experts, patient advocates, and representatives from US payers and both relevant pharmaceutical companies — convened to discuss the implications of the evidence for policy and practice. Key recommendations stemming from the roundtable discussion include:

  • All stakeholders should ensure that the introduction of new therapies for high cholesterol do not exacerbate existing health inequities and should strive to decrease inequity in the health care system by decreasing cost and access barriers for patients to access effective therapies. 
  • Payers should develop consistent prior authorization criteria for lipid-lowering drugs and assure that the documentation burden and other administrative elements of prior authorization do not create an unreasonable burden on clinicians and patients.
  • Manufacturers should set prices that will foster affordability and good access for all patients by aligning prices with independent assessments of the therapeutic value of their treatments. In particular, until cardiovascular outcomes data are available from ongoing trials, Novartis should fulfill its stated intent to set the price of inclisiran at or below the cost-effective range of pricing for PCSK9 inhibitors.
  • Researchers should seek to standardize definitions of ASCVD, major adverse cardiovascular events (MACE), and SASE (statin intolerance) in clinical trials to facilitate comparison of drugs and assist payers, clinicians, and patients in understanding which groups may benefit from a particular drug therapy.

ICER’s detailed set of policy recommendations, including considerations for establishing prior authorization criteria, is available in the Final Evidence Report and in the standalone Policy Recommendations document.

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.