In the short term, both lovo-cel and exa-cel can dramatically reduce the frequency of painful crises in patients with severe sickle cell disease —

Long term efficacy and safety have important uncertainties, particularly for exa-cel, the first CRISPR therapy to apply for FDA approval

— Current evidence suggests that lovo-cel and exa-cel would achieve common thresholds for cost-effectiveness if priced between $1.35M to $2.05M  —

— At the July 27 virtual public meeting, ICER’s independent appraisal committee will review the evidence, hear further testimony from stakeholders, and deliberate on the treatments’ comparative clinical effectiveness, other potential benefits, and long-term value for money —

BOSTON, July 13, 2023 – The Institute for Clinical and Economic Review (ICER) today posted its revised Evidence Report assessing the comparative clinical effectiveness and value of exagamglogene autotemcel (“exa-cel”, Vertex Pharmaceuticals and CRISPR Therapeutics) and lovotibeglogene autotemcel (“lovo-cel”, bluebird bio) for sickle cell disease. 

“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. “From the earliest days of gene therapy, patients, families, and clinicians have imagined that someday it might be possible to address the underlying genetics of sickle cell to achieve a cure. These first two genetic therapies, using different technologies and altering different genetic targets may mean that day has nearly arrived. However, the need for autologous bone marrow transplantation with these therapies means they come with important potential risks, and the first CRISPR therapy necessarily has even greater uncertainties about longer-term risks and durability of benefit than a lentiviral gene therapy.”

This Evidence Report will be reviewed at a virtual public meeting of the CTAF (CTAF) on July 27, 2023. The CTAF is one of ICER’s three independent evidence appraisal committees comprising medical evidence experts, practicing clinicians, methodologists, and leaders in patient engagement and advocacy.

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

Key Clinical Findings

For individuals with severe sickle cell disease, ICER found:

  • Lovo-cel provides at least an incremental net benefit compared with standard of care and may provide a substantial net health benefit.  We rated this comparison as “Incremental or Better” (B+).
  • Exa-cel may be comparable, result in incremental net benefit, or result in substantial net benefit when evaluated against standard of care.  We rated this comparison as “Comparable or Better” (C++).

Key Cost-Effectiveness Findings

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.

ICER’s HBPB is a price range suggesting the highest US price a manufacturer should charge for a treatment, based on the amount of improvement in overall health patients receive from that treatment, when a higher price would cause disproportionately greater losses in health among other patients in the health system due to rising overall costs of health care and health insurance. In short, it is the top price range at which a health system can reward innovation and better health for patients without doing more harm than good.

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.