— Evidence suggests that both resmetirom and obeticholic acid improve liver histology without evidence yet demonstrating improved long-term outcomes; obeticholic acid has more concerning side effects —

— Current evidence suggests that resmetirom would achieve common thresholds for cost-effectiveness if priced between $39,600 – $50,100 per year while obeticholic acid would achieve these thresholds if priced between $32,800-$40,700 per year —

— At the April 28 virtual public meeting, ICER’s independent appraisal committee will review the evidence, hear further testimony from stakeholders, and deliberate on the treatments’ comparative clinical effectiveness, other potential benefits, and long-term value for money —

BOSTON, April 13, 2023 – The Institute for Clinical and Economic Review (ICER) today posted its revised Evidence Report assessing the comparative clinical effectiveness and value of resmetirom (Madrigal Pharmaceuticals, Inc.) and obeticholic acid (Ocaliva®, Intercept Pharmaceuticals, Inc.) for non-alcoholic steatohepatitis (NASH). 

“NASH is increasingly common and lacks good therapies,” said David Rind, MD, ICER’s Chief Medical Officer. “While many with NASH will remain asymptomatic, some individuals will progress to severe liver disease and experience the complications of cirrhosis, hepatocellular cancer, and/or require liver transplantation. NASH is also a marker for increased cardiovascular risk and one of these therapies, resmetirom, improves lipids, while the other therapy, obeticholic acid, worsens lipids and also causes itching in many patients. If these drugs receive FDA approval, while awaiting long-term liver and cardiovascular data, patients and doctors will need to balance the risks, burdens, and potential benefits of each of these therapies.”

This Evidence Report will be reviewed at a virtual public meeting of the Midwest CEPAC (Midwest CEPAC) on April 28, 2023. 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

For resmetirom, ICER rated the evidence as comparable or better to the standard of care (C++).

For obeticholic acid, ICER rated the evidence for NASH with F2 fibrosis to be insufficient (“I”) and for NASH with F3 fibrosis, where patients are at higher risk of progression to cirrhosis, to be promising but inconclusive (“P/I”).

Key Cost-Effectiveness Findings

Both resmetirom and obeticholic acid are not yet approved by the FDA, and the manufacturers have not yet announced what the US prices will be if approved. ICER has calculated a health-benefit price benchmark (HBPB) for resmetirom to be between $39,600 – $50,100 per year.

ICER has calculated a health-benefit price benchmark (HBPB) for obeticholic acid to be between $32,800-$40,700 per year.

ICER’s 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.