High Costs of Sickle Cell Therapies Highlight Paradox of Drug Development

Newly developed gene therapies for rare diseases such as sickle cell disease (SCD) represent the pinnacle of scientific achievement, but they also underscore problems with the incentive structure underpinning modern therapy development, according to a new editorial.

Writing in the Journal of the American Medical Association, a team from Brigham and Women’s Hospital and Harvard Medical School argues that new approaches are necessary to balance the need for medical innovation with the economic realities of the modern health care system.¹

They said SCD offers an insightful example because the treatment landscape for the disease has been dramatically reshaped by gene-editing technology. The CRISPR-Cas9 platform was used to develop lovotibeglogene autotemcel (lovo-cel [Lyfgenia]; bluebird bio) and exagamglogene autotemcel (exa-cel [Casgevy]; Vertex/CRISPR Therapeutics), both of which have demonstrated the ability to dramatically reduce the risk of vaso-occlusive crisis leading to severe pain or organ damage.² Such advancements can be life changing for patients, but they also come with price tags ranging from $2.2 million (exa-cel) to $3.1 million (lovo-cel) per dose.

"While high prices may incentivize health care and biotechnology ecosystems to increasingly develop drugs for new diseases, high prices will conversely limit access to these treatments," the authors of this study wrote. | Image Credit: jadamprostore-stock.adobe.com

“While offering the possibility of tremendous benefit, these treatments also represent new challenges for patients, payers, and regulators,” the authors wrote.

SCD only affects about 100,000 people in the US, the authors said. Fewer patients means fewer customers for biopharmaceutical companies, and that, in turn, creates what they refer to as a “double-edged sword.”

“The paradox is that while high prices may incentivize health care and biotechnology ecosystems to increasingly develop drugs for new diseases, high prices will conversely limit access to these treatments, lead to higher out-of-pocket costs for those perhaps least able to afford them, and generate reluctance from insurers to cover multimillion-dollar products, compounding access problems,” they wrote.

The authors noted that SCD has historically received comparatively little attention from researchers and drug developers. For instance, a 2020 analysis comparing spending on SCD research to that of cystic fibrosis, another severe autosomal recessive disorder, found federal funding for cystic fibrosis was more than 3 times greater than funding for SCD research on a per-patient basis over a 10-year period.³ Foundation funding was even more dramatically disparate, with foundations spending about $7690 per patient with cystic fibrosis compared with just $102 per patient with SCD. Those spending disparities were associated with higher numbers of clinical trials and therapy approvals for cystic fibrosis.

One could argue, the authors said, that the high price of drugs like exa-cel and lovo-cel are justified insofar as they help offset such historic inequities faced by patients living with SCD.

Yet, the authors said charging millions for SCD therapies could lead payers to deny coverage, and drive up out-of-pocket health care costs for patients.

“These higher out-of-pocket costs might therefore further penalize patients for the historical neglect of such conditions and may exacerbate existing health disparities, especially for low-income patients,” they wrote.

They noted that a pilot program recently launched by the Center for Medicare and Medicaid Innovation could broaden access to SCD therapies, through features like price negotiation for gene therapies and manufacturer rebates if the therapies do not reach certain efficacy benchmarks.

Going forward, however, they said the government and other interested parties should consider alternate funding approaches to underwrite research. For instance, they said federal grant programs could be used to incentivize the development of therapies for underinvested diseases; such a model could offset research costs without necessarily increasing list prices. Grant programs could also be used to fund clinical trials or reward developers for completing trials in underinvested diseases, they wrote. In exchange, developers could be made to agree to price limits should the trials result in new therapies.

They noted that in the 2010s, the NIH used a grant-based program to spark SCD investigation and that research helped lead to the development of the exa-cel and lovo-cel.

Ultimately, they said, the example of SCD shows the need for incentive structures that promote health equity.

“Such incentives must simultaneously encourage the profitable development of therapies for underserved diseases and populations, while ensuring that these very people are able to access the breakthroughs once they are discovered,” they said.

References

1. Cliff ERS, Tessema FA. The double-edged sword of extremely high prices for gene therapies in sickle cell disease. JAMA. Published online August 5, 2024. doi:10.1001/jama.2024.11703

2. FDA approves first gene therapies to treat patients with sickle cell disease. FDA. News release. December 8, 2023. Accessed August 5, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapies-treat-patients-sickle-cell-disease

3. Farooq F, Mogayzel PJ, Lanzkron S, Haywood C, Strouse JJ. Comparison of US federal and foundation funding of research for sickle cell disease and cystic fibrosis and factors associated with research productivity. JAMA Netw Open. 2020;3(3):e201737. doi:10.1001/jamanetworkopen.2020.1737