Transformative Therapies for Sickle Cell Disease: A Global Stakeholder Perception Study on Advanced Cell Therapies

Sickle cell disease (SCD) is a global genetic blood disorder most prevalent in people of African and Indian ancestry with an estimated 750 million patients worldwide. Recent advancements in transformative therapies (TT), such as stem cell transplantation (HSCT) and gene therapy (GT)offer hope for disease mitigation. A definitive framework for patient selection and provider preference has yet to be established. This is the first global study conducted to explore healthcare providers (HCPs) perceptions of these transformative therapies and how it may impact patient selection for such arduous but promising treatment options.

Methods: A structured questionnaire was administered to HCPs involved in the care of SCD patients shortly after the US FDA approval for two GT in December 2023. Demographic data on medical specialty, familiarity with TT, center preparedness amongst respondents categorized by training, geographic location, and racial background etc. was analyzed to assess trends and perceptions. Descriptive statistics, and correlation analyses were used to explore relationships between demographic variables and survey responses. The data analysis included generating heat maps, identified significant correlations, and provided comprehensive overview of HCP perceptions.

Results: Responses from 30 HCPs with diverse global backgrounds (US, Asia, Europe, Africa) were analyzed. Highest respondents were based in urban centers and were specialized in oncology (35%). The racial background analysis revealed that respondents identifying as White/Caucasian and Asian/Pacific Islander were most familiar with GT (85%), while only 15% of Black respondents reported familiarity with this therapy. HCPs reported high familiarity with HSCT, particularly pediatric subspecialists. Familiarity with GT (43.3%) was also significant but slightly lower compared to HSCT (53.3%). A notable 82% of respondents considered HSCT and 72% GT more effective than standard SCD care. Exagamglogene autotemcel(EA) was the preferred gene therapy (20%), followed by lovotibeglogene autotemcel(L) (16.7%), 63.3%had no preference. Potential for cure (76.7%), reduction in pain (70%) for HSCT and no concern of graft versus host disease potential for GT, were most notable reported advantages of HSCT. Myeloablation (60%), multiple rounds of cell collection (40%), lack of access to fertility preservation (40%), cost (46%) were the chief unmet needs of TT for SCD in 2024.For the global participants cost and lack of access to GT was the chief unmet need and Cost significantly influenced treatment decisions for HSCT in Asia, Europe and Africa. 46% prioritized cost when selecting GT for LA, compared to 36% for EC GT. Access to a qualified treatment center (56%), multiple collections (36%) for EC and concern for secondary malignancy (46.6%) for LA were additional concerns highlighted by the respondents for GT perceptions. This significant financial barrier highlights the necessity for strategies to mitigate costs and ensure broader access to curative therapies globally.

Correlation Analysis: A heatmap analysis revealed a strong positive correlation among respondents were more familiar with GT rated it as more effective, emphasizing the importance of continued education and awareness to shape perceptions of emerging treatments. This study is the first of its kind to explore global perceptions and demographic trends concerning GT in SCD.

Trends Over Time: Majority (43.4%) reported expecting to see >5%of their patient's receiving GT over the next five years. Respondents filling out the survey in early 2024 reported higher familiarity and perceived effectiveness for GT as compared to the ones responding later in the year. The timing of F.D.A. approval for GT in December 2023 and social attention of that announcement presumably played a factor signifying a need for continuous education to sustain awareness and understanding among stakeholders involved in decision making for TT.

Conclusion: Our study offers novel insights into the outlook on TT for SCD. It highlights fertility preservation, access to QTC, risk of secondary malignancy and cost barriers critical factors in patient selection. Future research should focus on expanding the donor pool for HSCT, gathering long-term data on GT's safety and efficacy, and developing strategies to alleviate the financial burden associated with these TT.

Jain:Beam Therapeutics: Other: End point adjudication committee; Blue Bird Bio: Other: End point adjudication committee ; NovoNordisk: Speakers Bureau; Hemex Health: Consultancy; Sanofi: Speakers Bureau. Abdel-Azim:J&J: Other: Advisory Committee; Vertex: Other: Advisory Committee; Adaptive: Other: Speaking/teaching , Advisory Committee and Research Funding.