ICER Publishes Final Report and Policy Recommendations for Hemophilia A Therapies

— Independent appraisal committee votes that evidence is adequate to demonstrate clinical superiority of emicizumab over factor VIII prophylaxis; emicizumab is also cost saving, but only because factor VIII prices remain so high —

— Due to FDA's Complete Response Letter requesting longer-term data for valoctocogene roxaparvovec, there was no vote on its clinical effectiveness or cost-effectiveness; ICER's preliminary analyses using a placeholder price of $2.5 million suggested that it would also be cost saving when compared to the high costs of current factor VIII dosing levels; for one-time treatments such as gene therapies, policymakers should consider alternative approaches to value-based pricing that share more of the long-term cost offsets with the health system —

— Experts on policy roundtable recommend that life sciences companies and payers work together to de-escalate prices for current and future hemophilia treatments, recognizing that the current pricing structure creates financial toxicity for patients and their families, financial toxicity for health systems, and builds a platform for pricing potential cures that will only exacerbate these problems —

BOSTON, November 20, 2020 - The Institute for Clinical and Economic Review (ICER) today released an Final Evidence Report and Report-at-a-Glance assessing the comparative clinical effectiveness and value of valoctocogene roxaparvovec (Roctavian™, BioMarin Pharmaceutical) and emicizumab (Hemlibra®, Genentech) for the treatment of hemophilia A. In August 2020, BioMarin received a Complete Response Letter from the FDA requesting an additional two years of follow-up safety and efficacy data on valoctocogene roxaparvovec, and that process may delay the gene therapy's US approval decision until at least 2022. ICER previously assessed emicizumab when the treatment was approved by the FDA in 2017 with an indication of treating the subset of individuals with hemophilia A who have inhibitors to the clotting protein factor VIII; reflecting emicizumab's expanded indication in 2018, this year's report assesses the value of the treatment in individuals who do not have such inhibitors.

"Emicizumab reduces burdens on patients and caregivers and may improve patient outcomes while producing overall cost savings in the US healthcare system," said David Rind, MD, ICER's Chief Medical Officer. "However, emicizumab can be cost-saving at its own very high price only because it is being compared to the unnecessarily high costs in the US of prophylaxis with factor VIII. These prices — in a space with multiple products and manufacturers — represent a market that is failing people with hemophilia, who face financial toxicity from insurance cost sharing and the erosion of access due to escalating costs. Ultimately, prices that exceed the value to patients harm everyone, and especially vulnerable patients and families, trying to keep up with the rising costs of health insurance."

ICER's report on these therapies was reviewed at the October 2020 public meeting of the New England CEPAC (New England CEPAC), one of ICER's three independent evidence appraisal committees.

Voting on Clinical Effectiveness and Contextual Considerations

During the public meeting, New England CEPAC panelists voted unanimously that, for individuals with hemophilia A without inhibitors to factor VIII, the evidence is adequate to demonstrate that emicizumab provides a net health benefit over prophylaxis with factor VIII. No vote was taken regarding the comparative clinical effectiveness of valoctocogene roxaparvovec, due to the FDA's request for additional outcomes data.

During their deliberation, panel members also weighed the treatments' other potential benefits, disadvantages, and contextual considerations. As examples, a majority or plurality of the panel voted that:

  • Emicizumab's delivery mechanism or relative simplicity of regimen is likely to result in much higher real-world adherence and better outcomes relative to factor VIII than estimated from clinical trials;
  • Emicizumab will differentially benefit a historically disadvantaged or underserved community; and
  • Emicizumab will significantly reduce the negative impact of hemophilia A on family and caregivers when compared to factor VIII prophylaxis and will also have a significant impact on improving return to work and/or overall productivity when compared to factor VIII prophylaxis.

Cost-Effectiveness Findings and Voting on Long-Term Value for Money

No vote was taken on the long-term value for money of emicizumab because ICER's analysis found the treatment to be cost saving. In addition, no cost-effectiveness vote was taken on valoctocogene roxaparvovec because longer term outcomes data are pending, and the price of the therapy is not yet known.

For these same reasons, ICER did not calculate health-benefit price benchmarks for either treatment.

Key Policy Recommendations  

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

  • Pricing of factor VIII represents a failure of competition and is far too high, even in light of factor VIII's substantial benefits for patients; this pricing structure creates financial toxicity for patients and their families, financial toxicity for health systems, and builds a platform for pricing for potential cures that will only exacerbate these problems. In order to facilitate broad access to the current standard for clinically superior care, both in the US and abroad, drug makers should commit to pricing Factor VIII so that the cost to achieve trough levels of 3-5% is the same or lower than what it cost in the past to achieve a 1% trough level.
  • Trials of gene therapies for hemophilia need to be long enough to assess whether the benefits are durable enough to outweigh the risks, particularly since patients may be unlikely to be able to receive a second gene therapy using the same viral vector.
  • Payers should cover factor VIII prophylaxis at levels adequate to achieve higher troughs than the 1% level used in the past. In addition, considering the evidence of equivalent-to-improved comparative effectiveness, patient preference, and lower overall cost, payers should work with clinicians and patients to encourage the use of emicizumab over factor VIII for prophylaxis, unless it is contraindicated. Payers should also explore innovative approaches to covering high-impact single time therapies such as future gene therapies for hemophilia.
  • Patient groups should fully embrace their power to speak explicitly about the impact of the high prices of treatments for hemophilia A. General statements of concern about "costs" shift the focus subtly away from prices, which is consistent with the interests of the life science industry. Doing so deflects from the reality that drug makers have the power to set prices in the United States, and the result produces affordability concerns for health systems, financial toxicity for patients and families, and barriers to the ability of patients to gain access to optimal clinical care. Hemophilia patient groups should be willing to name the problem and bear witness to the harms that excessive prices cause.

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.

ICER looks forward to working alongside the hemophilia community to advocate for future clinical and real-world evidence on patient-important outcomes, and to facilitate negotiations between payers and manufacturers that ensure high-value therapies remain accessible to all patients. We remain hopeful that innovative gene therapies may one day help alleviate families' lifetime burden — a burden of illness, access restrictions, and personal finance.

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.