ICER Publishes Final Evidence Report on Gene Therapies for Sickle Cell Disease

— Despite uncertainty regarding longer-term outcomes, lovo-cel and exa-cel both estimated to produce substantial gains in length and quality of life; independent appraisal committee voted that currently available evidence is adequate to demonstrate a net health benefit over standard of care —

— Current evidence suggests that lovo-cel and exa-cel would achieve common thresholds for cost-effectiveness if priced between $1.35M to $2.05M; recommendations encourage drug makers to set prices toward lower end of this range to facilitate access and affordability across all insurance systems —

—  Payer recommendations highlight the importance of using the FDA label as the guide to coverage policy without narrowing coverage by including specific clinical trial restrictions unrelated to the likelihood of benefit from treatment —

BOSTON, August 21, 2023 – The Institute for Clinical and Economic Review (ICER) today released a Final Evidence Report assessing the comparative clinical effectiveness and value of exagamglogene autotemcel (Casgevy, “exa-cel”, Vertex Pharmaceuticals and CRISPR Therapeutics) and lovotibeglogene autotemcel (Lyfgenia, “lovo-cel”, bluebird bio) for sickle cell disease (SCD). 

ICER’s report on these therapies was the subject of the July 2023 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

“Sickle cell disease can affect nearly every organ system in the body, and severe sickle cell disease affects nearly every aspect of a person’s life,” said ICER’s Chief Medical Officer, David Rind, MD. “In the US, it is a disease that heavily affects the American descendants of those who were forcibly brought here as slaves. As such the US government and US payers have special obligations to ensure access to these new transformative gene therapies for sickle cell disease, and US manufacturers have special obligations to price such therapies low enough to facilitate broad access so as to maximize benefits for this population that has suffered historic harms and ongoing discrimination.”

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

For adolescents and adults with severe SCD who do not have access to, or cannot receive, hematopoietic stem cell transplantation (HSCT) from a matched sibling or haploidentical donor:

A majority of panelists (13-1) found that current evidence is adequate to demonstrate a net health benefit for exa-cel when compared to standard of care (i.e., hydroxyurea, chronic blood transfusions, pain medication, iron chelation).

A majority of panelists (13-1) found that current evidence is adequate to demonstrate a net health benefit for lovo-cel when compared to standard of care (i.e., hydroxyurea, chronic blood transfusions, pain medication, iron chelation).

All panelists (14-0) found that current evidence is not adequate to distinguish the net health benefit between exa-cel and lovo-cel.

During their deliberations, panel members also weighed potential benefits and disadvantages beyond the direct health effects, and broader contextual considerations. Voting highlighted the following as particularly important for payers and other policymakers to note:

The acuity of need for treatment of individual patients based on short-term risk of death or progression to permanent disability;

The magnitude of the lifetime impact on individual patients of sickle cell disease;

The likelihood that these new treatments will improve patients’ broader ability to achieve major life goals related to education, work, or family life;

The likelihood that these new treatments will improve caregivers’ quality of life and/or ability to achieve major life goals related to education, work, or family life;

The likelihood that these new treatments will improve patients’ ability to manage and sustain treatment given the complexity of regimen;

The likelihood that these new treatments will meaningfully address society’s goal of reducing health inequities.

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

Both lovo-cel and exa-cel have not yet been approved by the FDA, and the manufacturers have not announced US prices if approved. ICER has calculated a health-benefit price benchmark (HBPB) for lovo-cel and exa-cel to be between $1.35M to $2.05M.

Consistent with ICER’s process, because there is no firm estimate yet of a potential launch price for both treatments, the panel did not take separate votes on the treatments’ 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 the manufacturers, 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:

If the announced prices for lovo-cel and exa-cel align with expected patient benefits and are set toward the lower edge of their estimated cost-effectiveness ranges, payers should use the FDA label as the guide to coverage policy without narrowing coverage by including specific clinical trial restrictions unrelated to the likelihood of benefit from treatment.  

Manufacturers should work with payers to create meaningful alternative payment models that can address two key distinguishing features of gene therapies: 1) the significant short-term budget impact; and 2) the considerable uncertainty regarding longer-term safety and benefits.

Manufacturers and the clinical research community should develop cohort studies and real-world evidence programs to evaluate the longer-term safety and durability of gene therapies.  

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.