Study Finds Patients With Severe Sickle Cell Disease Show High Interest in Potentially Curative Gene Therapies

According to a recent study published in Blood Advances, individuals with severe sickle cell disease (SCD) show high interest in potentially curative gene therapy treatments and are willing to accept associated risks for a chance at a cure. Currently, standard of care for SCD includes medications such as hydroxyurea, which helps with symptom management, and bone marrow transplant that can cure SCD if successful; however, transplant is dependent on finding a matched donor and carries high risk of rejection.

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“In recent decades, [United States] survival rates for SCD patients have significantly risen, but the average life expectancy is about 60 years—substantially lower than that of the general population,” said lead study author Juan Marcos Gonzalez, PhD, an expert in clinical decision sciences and health-preference measurement at Duke University School of Medicine, in a press release. “Although current therapies are beneficial, many patients will not qualify for a bone marrow transplant and the other therapies will not eliminate SCD symptoms entirely.”

Emerging gene therapies for SCD extract hematopoietic stem cells (HSCs) from patients with SCD and edit the DNA within the cells to remove the mutation that causes abnormal red blood cell development. In addition, the patients receive high doses of chemotherapy followed by reinfusion of gene-corrected HSCs, which produce normal, mature red blood cells. Gene therapy products for blood disorders, cancers, and other rare diseases have also developed; however, the risk-benefit tradeoff is currently not well-established.

Study authors used a choice experiment survey, which presented enrolled participants with pairs of hypothetical gene therapy treatments along with a “no gene therapy” option. Gene therapy choices were characterized by their potential to eliminate SCD symptoms, extend life expectancy, and their associated risks (eg, treatment-related mortality, infertility, and increased cancer risk).

Most survey respondents were more willing to choose gene therapy over alternatives; however, when gene therapy posed a 10% or greater risk of death, adults experiencing mild symptoms (approximately 67%) required a higher likelihood of eliminated SCD symptoms than parents of children (approximately 8%) to select gene therapy. Alternatively, adults with moderate symptoms required lower success rates. Further, for gene therapies posing 10% or 30% mortality risks, these patients required 34% and 37% chance of having their SCD symptoms fully resolved to accept treatment, respectively.

“From this study we see that adults and parents of children with SCD are willing to endure a relatively high level of risk to have their disease symptoms alleviated,” said Gonzalez in the press release. “I think that this demonstrates just how burdensome this disorder is. Parents would show us videos of their children crying because they were having pain crises. As a parent, there's nothing more gut-wrenching than seeing your child in excruciating pain and not being able to do anything about it.”

The authors note that although gene therapies indicate a significant breakthrough in the treatment of SCD, they are expensive, and cost was not factoring into survey questions. In addition, the study only evaluated patient opinions of 1 kind of gene therapy that used CRISPR-Cas9 technology, meaning that risks and benefits may differ across other therapies.

“Numerous different approaches to gene therapy have emerged since we began this study,” said Gonzalez in the press release. “As different types of gene therapies gain approval, patients and their providers will have to decide what is best for them. We hope to continue exploring patients’ understanding and willingness to try new therapies in years to come.”

Reference

American Society of Hematology. Individuals with severe sickle cell disease express high risk tolerance for gene therapies. News release. October 31, 2023. Accessed November 8, 2023. https://www.eurekalert.org/news-releases/1006398