— Independent appraisal committee determines the evidence is not adequate to demonstrate that roxadustat provides a net health benefit over erythropoiesis-stimulating agents (ESAs); until greater net benefit is proven, value-based pricing would suggest that roxadustat be priced at most at parity with ESAs —

— At policy roundtable, experts emphasize the need for researchers to continue to gather comparative data across more ethnically and racially diverse patient subgroups —

BOSTON, March 5, 2021 – The Institute for Clinical and Economic Review (ICER) today released a Final Evidence Report assessing the comparative clinical effectiveness and value of roxadustat (FibroGen) for treatment of anemia in chronic kidney disease (CKD). The California Technology Assessment Forum (CTAF), one of ICER’s three independent evidence appraisal committees, deliberated over these findings and took votes on the strength of evidence on comparative clinical effectiveness at a February 2021 public meeting. Two weeks after ICER’s public meeting, FibroGen announced that the FDA now plans to convene a public advisory committee meeting to discuss roxadustat’s new drug application.

Downloads: Final Evidence Report | Executive Summary | Policy Recommendations

“Roxadustat represents an oral alternative for patients living with anemia from CKD, and as such, it may offer important advantages for those not receiving in-center hemodialysis” said David Rind, MD, MSc, ICER’s Chief Medical Officer. “However, given prior concerns around cardiovascular risks when ESAs are used to correct anemia, as well as the high baseline risk of cardiovascular events in people with CKD, the effect of roxadustat on cardiovascular events and all-cause mortality is of particular concern. The drug maker has conducted multiple trials examining this issue, but although these trials ended several years ago, the company has not yet made public a number of analyses that we feel are necessary to answer several key questions. This leaves large uncertainties about the balance of risks and benefits of roxadustat, and the votes of the CTAF panel confirmed these concerns.”   

Voting on Clinical Effectiveness and Contextual Considerations

During the public meeting, the CTAF panelists voted unanimously (15-0) that the evidence is not adequate to demonstrate that roxadustat provides a net health benefit over ESAs. Further, for the population of patients who are dialysis independent (DI-CKD), and for whom ESAs were not available (i.e., where those patients would otherwise receive blood transfusions), the CTAF also voted unanimously (15-0) that the evidence is not adequate to demonstrate roxadustat provides a net health benefit over usual care.

During their deliberations, panel members also weighed roxadustat’s other potential benefits, disadvantages, and contextual considerations. A majority affirmed that:

  • Roxadustat represented a new mechanism of action compared to that of other active treatments;
  • Roxadustat’s delivery mechanism or relative simplicity of regimen is likely to result in higher real-world adherence and better outcomes relative to ESAs than estimated from clinical trials; and
  • ICER’s economic model assumptions posed no significant risk that base-case cost-effectiveness estimates were too optimistic or pessimistic.

Voting on Long-Term Value for Money

The CTAF did not vote on roxadustat’s long-term value for money because the evidence is insufficient to know whether roxadustat provides a net health benefit over an ESA.

ICER’s economic modeling shows that, at a placeholder price of $6,500 per year, roxadustat may be cost saving in the DI-CKD population with similar or improved benefit, but this includes a high degree of uncertainty. In the dialysis dependent population (DD-CKD), roxadustat may increase mortality compared with ESAs; in the absence of evidence that it is superior to ESAs, value-based pricing would suggest roxadustat cost no more than ESAs.

Key Policy Recommendations  

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

  • Given the level of uncertainty about the benefits versus harms and the long-term effect of using roxadustat compared to ESAs, ICER strongly suggests a mandate for a registry or other rapid and comprehensive post-marketing assessment.
  • The manufacturer should not hold data in confidence from RCTs completed more than one to two years ago. The company has a responsibility to patients and clinicians to move these data into the public domain, to submit data rapidly for peer review in advance of regulatory approval, and to share these data in a transparent manner with groups seeking to assess the evidence to inform clinical practice and policy.
  • If roxadustat gains regulatory approval, the manufacturer should price the drug in alignment with its demonstrated value, which at the current time is highly uncertain given the lack of clarity about overall mortality and cardiovascular outcomes. In this setting, with significant uncertainty of this magnitude, the manufacturer should set the price lower than treatments with more established evidence and wait until further evidence addresses the uncertainties before seeking a higher price.
  • The manufacturer and researchers should avoid focusing primarily on Hb levels and the need for transfusion. Future research should expand outcomes measured to include patient-relevant outcomes such as quality of life, functional status, fatigue, overall cardiovascular events, and mortality in addition to the need for transfusion.

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.