Access to Gene Therapy in Sickle Cell Disease

Introduction: Sickle cell disease (SCD) is an inherited blood disorder that results in hemolysis and intermittent episodes of vaso-occlusion, which can progress to severe episodes with organ involvement. It is a lifelong chronic illness and can have significant morbidity and early mortality. Given the significant disease burden, curative therapies with bone marrow transplantation (BMT) have been considered, particularly in patients with severe disease in childhood. However, there are still significant limitations including a limited donor pool. The FDA approved two new gene modification therapies in December of 2023 to help bridge this gap. These transformative therapies offer the opportunity to overcome the donor barriers and may be considered a potential breakthrough in SCD treatment. In this study we sought to determine how the patients in our clinics have approached this new therapy with their treatment teams. In particular, we examined potential barriers patients may experience when considering these curative and transformative therapies.

Methods: We conducted a retrospective IRB-approved observational study at the Levine Cancer Institute (LCI) and Wake Forest School of Medicine (WFSOM). Using our patient databases, we identified patients with SCD seen from December 8^th, 2023 - May 31^st, 2024 who had discussed BMT and gene modification therapies with their clinical teams. We then extracted information on demographic and clinical characteristics as well as medical and socioeconomic barriers to curative therapies and analyzed these data with descriptive statistics. Continuous variables are reported as means, medians and ranges while categorical variables are reported as frequencies and percentages. Fisher's exact test was utilized for categorical variables, and the Wilcoxon rank-sum test was utilized for continuous variables.

Results: Of 421 patients identified, 130 (30.9%) had discussed BMT and gene therapy with their clinical teams. Patients who discussed transformative therapies were significantly younger that those who did not (median age 21 vs. 36 years, p < .0001). Patients with the SS and Sβ⁰ genotypes were significantly more likely to have discussed these therapies than those with other genotypes (80.8% vs. 59.5%, p < .0001). The majority of patients (58.5%, 76 of 130) who discussed transformative therapies with their clinical teams were interested in further discussions. Only 12.3% were candidates for BMT based on the availability of matched sibling donors. Additionally, 10.8% of patients had organ dysfunction that was concerning to the medical team for tolerance of BMT or gene modification therapy. Other commonly identified barriers were limited social support (14.6%), financial concerns (17.7%), and responsibilities as caregivers to others (15.4%).

Conclusion: Our data indicate that a substantial proportion of patients with SCD receiving care at our institutions are interested in curative therapies. Medical limitations, including lack of a matched sibling donor and organ dysfunction, are limiting factors for eligibility. Preventing organ dysfunction, particularly renal and CNS disease will be key for future eligibility for patients. Additionally, socioeconomic concerns pose key barriers to access. We believe these data will inform future patient education and resource allocation, which will be necessary to overcome disparities that may limit patient access to BMT and gene modification therapy.

Desai:Chiesi: Honoraria; Novartis: Research Funding; Novo Nordisk: Research Funding; Pfizer: Consultancy, Research Funding; NMDP: Other: Study Monitor . George:Cheisi: Honoraria.