ICER to Assess Clinical Effectiveness, Value of 2 NASH Treatments


There are no FDA-approved therapies for nonalcoholic steatohepatitis (NASH), but there are many being developed. Resmetirom and obeticholic acid are both being reviewed by the FDA with decisions expected in 2023.

The prevalence of nonalcoholic steatohepatitis (NASH) is estimated to be between 1.5% and 6.5% of adults in the United States. Treatment is limited to lifestyle changes, such as exercise and weight loss, because there are no FDA-approved therapies for NASH. However, there are multiple pharmacologic treatments in development.

The Institute for Clinical and Economic Review (ICER) is planning to assess the comparative clinical effectiveness and value of 2 treatments for NASH: resmetirom and obeticholic acid (OCA). ICER released a draft scoping document developed with input from patients and their families, clinicians, researchers, and manufacturers.

OCA is approved for the treatment of primary biliary cholangitis and a decision on it for the treatment of NASH with fibrosis is expected in 2023. Interim data announced in July by Intercept, the company developing OCA for NASH with fibrosis, showed an improvement in liver fibrosis without worsening of NASH after 18 months. The REGENERATE trial included patients with liver fibrosis due to NASH. However, in the REVERSE trial, which included patients with compensated cirrhosis due to NASH, the drug did not meet the primary end point of at least a 1-stage histological improvement in fibrosis with no worsening of NASH at 18 months.

In 2020, ICER reviewed OCA for the treatment of NASH with fibrosis. At the time, ICER determined that the long-term net effects of OCA on the quality of life and health of patients with NASH and fibrosis were uncertain and evidence was insufficient.

Resmetirom is a small molecule agonist for the thyroid hormone receptor beta, and it is under review with the FDA to treat NASH with fibrosis. A decision is also expected in 2023. According to topline results released by Madrigal, the company developing resmetirom, the drug was safe and well-tolerated and helped patients with presumed NASH achieve significant, clinically relevant reductions in liver fat.

ICER’s review of OCA and resmetirom will aim to compare the agents to one another and to usual care. The outcomes of interest include all-cause mortality, cirrhosis, health-related quality of life, hepatocellular carcinoma, liver transplant, NASH symptoms, adverse events, resolution of NASH, and changes in nonalcoholic fatty liver disease activity score.

Other benefits and contextual considerations will also be reviewed. These include:

  • Acuity of need for treatment
  • Magnitude of lifetime impact
  • Patients’ ability to achieve major life goals
  • Caregivers’ quality of life and/or ability to achieve major life goals
  • Patients’ ability to manage and sustain treatment
  • Society’s goal of reducing health inequities

ICER is looking for input on these elements during the public comment period, which is open until October 26, 2022. A revised document incorporating public comments will be posted on November 3, 2022.

The review will also include an economic model to assess the lifetime cost-effectiveness of the 2 treatments. Another analysis will explore the health system budgetary impact of treatment over 5 years.

“This budgetary impact analysis will indicate the relation between treatment prices and level of use for a given potential budget impact, and will allow assessment of any need for managing the cost of such interventions,” according to the scoping document.

The report will be discussed during the meeting of ICER’s Midwest Comparative Effectiveness Public Advisory Council (CEPAC), a nationally recognized independent appraisal committee. Midwest CEPAC will meet in April 2023, and an independent evidence review panel will discuss the findings and vote on the evidence presented in the report.

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