Exploring the Patient Perspective of Gene Therapy for Sickle Cell Disease
Authors: Nimura Clare , Gonzalez Lisbel , Brown Tatum , Van Doren Layla N , Karkoska Kristine , Jacob Seethal A , Azar Sharl , Boucher Alexander A , McGann Patrick T. 
Published: December 2024

Background: With the FDA approval of two gene therapies for sickle cell disease (SCD) in December 2023, and more in clinical trials, we are at the precipice of transformative care for SCD. Although gene therapy has been shown to be cost-effective in simulated analyses, it remains an expensive and intensive treatment option. The access to and potential uptake of these treatments among the estimated 100,000 Americans living with SCD is unclear. Limited research has examined attitudes and perspectives on gene therapy among individuals with SCD and their caregivers, and none since FDA approval. It is unclear if patients/caregivers are adequately informed about or interested in gene therapy, and what factors influence their decision to consider it as a treatment option.
Objectives: (1) Assess perception and knowledge of gene therapy among patients with SCD and their caregivers. (2) Provide education about gene therapy to patients/caregivers. (3) Explore patients' willingness to receive gene therapy after receiving education.
Methods: In this cross-sectional study, we examined attitudes and understanding of gene therapy as a treatment option among pediatric and adult patients with SCD or their caregivers. A three-part REDCap survey was completed by 49 participants. Part I collected demographic information and surveyed patients/caregivers about their current understanding of gene therapy for SCD. Part II provided education on gene therapy: mechanism, eligibility, treatment timeline, and potential risks and benefits based on published data. Finally, Part III surveyed patient/caregiver willingness to receive gene therapy and key factors influencing their decision.
Results:
Patient demographics and current treatments:
The 49 survey participants included 65.3% patients and 34.7% caregivers on behalf of a patient. The responses included 67.3% adult patients and 32.7% pediatric patients with SCD: 57.1% had the SS genotype, 28.6% had SC, and 12.2% had Sβ+-thalassemia. There was a range in disease severity, with 49.0% of patients reporting ≥3 visits to the emergency department due to SCD in the past 2 years. Most patients experienced acute and/or chronic pain (81.6% acute, 57.1% chronic), with 46.9% of patients experiencing pain daily or weekly. Many reported additional complications such as acute chest syndrome, cholecystitis, and avascular necrosis. 83.7% of patients were currently receiving disease modifying therapy in the form of hydroxyurea (65.3%) and regular blood transfusions (18.4%).
Perspectives on gene therapy:
We found that 75.5% of patients/caregivers had awareness of gene therapy for SCD, with the medical team and media (news or internet) being the primary sources of information (54.1% and 40.5%). Most patients/caregivers (59.2%) felt “not at all knowledgeable” or only “slightly knowledgeable” about gene therapy, with a wide range in perceived safety and efficacy. After reviewing the brief in-survey education, patients/caregivers reported feeling more knowledgeable about gene therapy and perceived gene therapy as safer, but the perception of efficacy remained varied and interest in receiving the treatment was essentially unchanged (24.5% “no,” 24.5% “yes,” 51.0% “maybe”). The greatest concerns about gene therapy were the risks of cancer (77.6%), financial consequences (67.3%), infection (63.3%), unanticipated side effects (57.1%), and infertility (51.0%). Over 80% of patients/caregivers reported that the potential benefits of improved quality of life, longer life expectancy, and benefit to others with SCD in the future would have “significant influence” on their decision to pursue gene therapy.
Conclusions: In this study we found that many patients/caregivers are interested in gene therapy as a treatment option for SCD. Interestingly, 2 in 3 patients had concerns about the financial toxicity of gene therapy beyond the cost of the product itself, highlighting the short- and long-term burden of these therapies. Our study is the first to examine patient/caregiver knowledge and perception of gene therapy since FDA approval and found wide variation in self-reported knowledge of gene therapy and perceived safety and efficacy of the treatment. Understanding knowledge gaps and perceptions of gene therapy among patients/caregivers can inform how physicians approach conversations about treatment options and can help align research questions with patients' needs.