ICER Publishes Final Evidence Report on Gene Therapies for Hemophilia A and B

— Fair pricing benchmarks suggest upper bounds for price of Roctavian at approximately $1.9 M and for Hemgenix at approximately $2.9 M —

— Payers should work with manufacturers to develop and implement outcomes-based agreements to address the uncertainty and the high cost of gene therapies for hemophilia —

— Clinical experts affirm that it would be inappropriate to require step therapy with
emicizumab prior to coverage for Roctavian —

BOSTON, December 22, 2022 – The Institute for Clinical and Economic Review (ICER) today released a Final Evidence Report assessing the comparative clinical effectiveness and value of etranacogene dezaparvovec (Hemgenix, CSL Behring) for hemophilia B. ICER also updated the previous Hemophilia A assessment on valoctocogene roxaparvovec (Roctavian™, BioMarin).  

ICER’s report on these therapies was reviewed at the November 2022 public meeting of the of the CTAF (CTAF), one of ICER’s three independent evidence appraisal committees.

Downloads: Final Evidence Report | Report-at-a-Glance | Policy Recommendations

“Hemophilia is a serious, lifelong disease, that leads to pain and disability as a result of repeated bleeds into joints and muscles, and can limit options for education, employment, and recreation,” said David Rind, MD, ICER’s Chief Medical Officer. “Prophylaxis with factor replacement is burdensome and does not achieve normal clotting although, for patients with hemophilia A, emicizumab has reduced burdens and improved outcomes. The new gene therapies can result in successfully treated patients appearing ‘cured’ for at least a period of time.  During this period, these gene therapies will eliminate the need for expensive prophylactic treatment. However, the duration of this ‘cure’ and the safety of therapies remain important uncertainties. At least with valoctocogene roxaparvovec, patients will eventually return to needing prophylaxis.”

Register for the ICER Analytics Hemophilia A and B Public Webinar

On January 19, 2023 ICER’s President Steven Pearson, MD, MSc and ICER’s Executive Vice President and Chief Operating Officer Sarah Emond, MPP will host a webinar to demonstrate how payers, manufacturers, policy makers, and others can leverage the results of ICER’s assessment on gene therapies for hemophilia A and B within ICER Analytics. Registration for the webinar is now open.

ICER’s Virtual Public Meeting: Voting Results on Clinical Effectiveness and Contextual Considerations

For adults ≥ 18 years of age with hemophilia B without inhibitors who would be appropriate for routine prophylaxis with factor replacement:

A majority of panelists (10-2, 1 abstained) found that the evidence is adequate to demonstrate a net health benefit of Hemgenix compared to prophylaxis with Factor IX.

For adults ≥ 18 years of age with hemophilia A without inhibitors who would be appropriate for routine prophylaxis with factor replacement:

A majority of panelists (11-2) found that the evidence is adequate to demonstrate a net health benefit of Roctavian compared to prophylaxis with Factor IX.

All panelists (13-0) found that the evidence is not adequate to demonstrate a net health benefit of Roctavian compared to prophylaxis with emicizumab.

During their deliberations, panel members also weighed the therapy’s other potential benefits, disadvantages, and contextual considerations. Voting highlighted the following as particularly important for payers and other policymakers to note:

Magnitude of the lifetime impact on individual patients;

Patients’ ability to achieve major life goals related to education, work, or family life;
Caregivers’ quality of life and/or ability to achieve major life goals related to education, work, or family life;
Patients’ ability to manage and sustain treatment given the complexity of regimen.

ICER’s Virtual Public Meeting: Voting Results on Long-Term Value for Money

ICER capped the cost offsets of a gene therapy at $150,000 per year, such that Hemgenix is credited with that amount as a maximum offset; however, factor IX prophylaxis often costs $750,000 per year or more. We felt that factor is extremely overpriced in the US and so limited the amount credited to such cost offsets. For Roctavian the HBPB ranges from $1.958 million to $1.963 million; and the relevant HBPB for Hemgenix is $2.93 million to $2.96 million.

After reviewing the clinical evidence and considering the treatments’ other potential benefits, disadvantages, and contextual considerations noted above, the CTAF evaluated the long-term value of Hemgenix at a manufacturer-suggested price of $4 million (higher than the eventual list price of $3.5 million):

At a price of $ 4 million, a majority of panelists found that Hemgenix compared to prophylaxis with Factor IX represents “low” or “intermediate” long-term value for money.  

Key Policy Recommendations:

ICER’s independent assessment of value informs the critical decisions that stakeholders across the US health system need to make around pricing and coverage. Following the voting session, a policy roundtable of experts — including clinical experts, patient advocates, and representatives from US payers — convened to discuss the pricing implications and recommendations to ensure fair access.  Key recommendations stemming from the roundtable discussion include:

The value of high-impact single and short-term therapies should not be determined exclusively by estimates of long-term cost offsets, particularly when the existing standard of care is acknowledged to be priced significantly higher than reasonable cost-effective levels.

Payers should work with manufacturers to develop and implement outcomes-based agreements to address the uncertainty and the high cost of gene therapies for hemophilia.


At least one national payer has suggested to patient representatives that step therapy with emicizumab is being considered prior to provision of coverage for Roctavian.  Clinical experts and patient experts view this approach as lacking any clinical justification and appears to be only a method for trying to avoid the high one-time fee for gene therapy while assuming that patients may switch insurers before the cost-saving potential of gene therapy is fully realized. In short, step therapy does not appear to be a reasonable consideration for this treatment.

ICER’s detailed set of policy recommendations, including comprehensive considerations for establishing evidence-based 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.