— Given the FDA’s recent decision to not grant accelerated approval for the treatment, ICER has canceled its August public meeting —

BOSTON, July 21, 2020 – The Institute for Clinical and Economic Review (ICER) today released an Evidence Report assessing the comparative clinical effectiveness and value of obeticholic acid (OCA, Intercept Pharmaceuticals) for the treatment of nonalcoholic steatohepatitis (NASH) with fibrosis.

Given the FDA’s recent Complete Response Letter stating the treatment’s current efficacy and safety data were insufficient to support accelerated approval, ICER announced we will no longer hold our August 2020 Midwest CEPAC public meeting to deliberate over the findings of this report.

“Although we do not know the reasons for the FDA decision, ICER’s review of OCA concluded that the potential cardiovascular risks of therapy led to uncertainties about whether treatment would be beneficial or harmful in many patients,” said David Rind, MD, ICER’s Chief Medical Officer. “Our review also highlighted how the large population of patients with NASH could lead to a very large budget impact for any expensive treatment for NASH, and this is likely to be an issue as many new treatments appear to be in the pipeline. Additionally, although the generic therapy pioglitazone is often said not to improve NASH fibrosis, our review found evidence that it may have similar effects on fibrosis to that of OCA, although the overall balance between benefits and harms with pioglitazone remains uncertain as well.”

Key Clinical Findings

For people living with NASH with fibrosis, OCA appears to reduce progression and promote regression of fibrosis compared with placebo. There is uncertainty about the long-term importance and benefit of these changes, but we assess that it is likely that OCA will reduce progression to cirrhosis, and thus improve certain patient-important outcomes over the long-term. However, the magnitude of this benefit is uncertain.

OCA commonly causes pruritus, so it can worsen quality of life in previously asymptomatic patients. OCA when used for primary biliary cirrhosis has had reports of severe harms with liver decompensation and death. Further, OCA raises LDL-C levels in patients who are already at high risk for CV disease, and given that CV death is the primary cause of death in patients with NASH, we are uncertain whether OCA will improve outcomes overall.

Viewing the evidence as a whole, we feel the long-term net effects of OCA on quality of life and health of patients with NASH and F2/F3 fibrosis are uncertain, and we judge the evidence for OCA in NASH with F2 fibrosis to be insufficient (“I”) and with F3 fibrosis to be promising but inconclusive (“P/I”).

Pioglitazone, a separate drug that has been available as a treatment for Type 2 diabetes mellitus (T2DM), has less convincing evidence of improving fibrosis than OCA, although the magnitude of effect appears to be similar to that of OCA. Pioglitazone may reduce CV events for people with T2DM, although given the risks of heart failure and weight gain, the balance between long-term benefits and harms in treating NASH remains uncertain. Therefore, we judge the evidence for pioglitazone in NASH to be promising but inconclusive (“P/I”).

In addition, we judge the evidence to be insufficient (“I”) to compare OCA with pioglitazone as treatments for NASH.

Potential Other Benefits and Contextual Considerations

Our reviews seek to provide information on potential other benefits offered by the intervention to the individual patient, caregivers, the delivery system, other patients, or the public that would not have been considered as part of the evidence on comparative clinical effectiveness.

For example, there are no currently approved drugs in the US for the treatment of NASH. In addition, either OCA or pioglitazone potentially could reduce patient fatigue and potentially improve productivity. However, there are significant concerns about the long-term risks of serious side effects with OCA, and there is also significant uncertainty around the magnitude and durability of the long-term benefits of both OCA and pioglitazone.

Key Cost-Effectiveness Results

Assuming that OCA as a treatment for NASH would be priced the same as Ocaliva® (obeticholic acid, indicated for the treatment of primary biliary cholangitis), the treatment would far exceed all commonly cited thresholds for cost-effectiveness. Should OCA be approved for the treatment of NASH, its ultimate cost effectiveness will be determined by the price that is set by the manufacturer and its long-term effectiveness.

ICER is not providing a health-benefit price benchmark (HBPBs) for OCA as a treatment for NASH with fibrosis given the FDA decision in June 2020 to issue a Complete Response Letter to the manufacturer. If OCA is approved in the future for this indication, additional evidence may be available at that time that could influence ICER’s HBPB results.

Potential Budget Impact

Even if OCA were to be launched with a price that met current cost-effectiveness thresholds – far lower than the current price of Ocaliva – only between 3-4% of eligible patients could be treated in a given year before crossing the ICER budget impact threshold of $819 million.

Due to the large population of individuals living with NASH in the US, other potentially expensive treatments in the pipeline may create similar short-term affordability and access challenges for patients and the health system.

Public Comments

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

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.