Background: Patients with severe sickle cell disease (SCD) experience vaso-occlusive crises (VOCs), which impact quality of life and contribute to organ damage and early mortality. An ongoing, open-label Ph3 clinical trial of exagamglogene autotemcel (exa-cel), an investigational, autologous, ex vivo CRISPR/Cas-9-based gene edited therapy in patients with severe SCD, is evaluating the proportion of patients who become VOC-free for at least 1 year after treatment. Real world data was used to generate estimates for clinical trial contextualization.
Objectives: To estimate the proportion of patients with severe SCD who are similar to patients eligible for the exa-cel clinical trial and are receiving real-world care who became VOC-free during 1-year follow-up.
Methods: Using Merative™ MarketScan® Commercial and Medicaid Databases from the years 2012-2019, a cohort of patients 12-35 years old with SCD was identified based on ≥1 inpatient claim or ≥2 outpatient claims for SCD. Unique VOC episodes were defined by emergency department or inpatient hospital claims (≤3 days apart) for acute pain crisis, acute chest syndrome, priapism, or splenic sequestration. Patients with severe SCD were defined as having ≥2 VOCs in each of 2 consecutive years (baseline period), consistent with exa-cel clinical trial inclusion criteria. Clinical trial exclusion criteria were implemented by excluding patients with claims for prevalent medical conditions (e.g., decreased kidney function) during the baseline period. Only patients with at least 1 year of follow-up after their baseline period were analyzed. The primary outcome was the proportion of patients with zero VOCs during follow-up. Subgroup analysis was performed based upon the number of VOCs during baseline.
Results: Of 33,292 total patients with SCD, 2,168 (7%) had sufficient claims data available and met the age and baseline VOC requirements. After applying exa-cel clinical trial exclusions, 1,518 (70%) patients met eligibility; mean age was 20.9 years with 56% female and 80% Medicaid. Patients had a mean of 5.3 VOCs during each year of baseline period. The proportion of patients with no VOCs during the 1-year follow-up was 11.7% (95% CI: 10.1%, 13.3%). Among patients with an average of ≥3, ≥4, and ≥5 VOCs per year during baseline, 6.5% (95% CI: 5.0%, 8.0%), 3.8% (95% CI: 2.4%, 5.2%), and 2.0% (95% CI: 0.8%, 3.2%) had no VOCs during follow-up, respectively.
Conclusions: The proportion of patients with severe SCD who become VOC-free for 1 year with real-world care is low (11.7%). The likelihood of becoming VOC-free is lower for patients with increasing numbers of previous VOCs per year. Administrative claims data can be used to estimate real-world outcomes and contextualize clinical trial results in SCD.
