Bridging the Gap for Sickle Cell Disease Patient Data in Sub-Saharan Africa By Expanding Access to Specialty Biomarkers and Clinical Trials

The pipeline of clinical trials for sickle cell disease (SCD) therapies has expanded substantially, exposing limitations in the existing clinical trial infrastructure. Clinical trials in the U.S. and Europe struggle with limited patient access. Conducting SCD clinical trials in sub-saharan Africa (SSA) could enable innovative therapies to reach the patients who experience the most significant burden of SCD.

There are several factors impacting the advancement of clinical trials in SSA including understanding cultural nuances, supply chain issues and lack of specialty laboratory infrastructure needed to generate data that meets the quality standards for clinical research in the U.S. and Europe. We hypothesized that quality standards of a US-based RBC specialty lab could be reproduced in Nigeria, for proprietary biomarkers including flow adhesion of whole blood to vascular adhesion molecule (FA-WB-VCAM), P-selectin (FA-WB-Psel) and LoRRCA.

We replicated a Detroit, MI-based clinical site and RBC specialty lab in Awka, Nigeria. Standard operating procedures (SOPs) from the Detroit site were transferred, and training was provided to the Nigeria-based lab team for LoRRA and the proprietary FA-WB-VCAM, FA-WB-Psel assays. Blood samples were obtained from individuals with documented HbSS based on patient records.

Whole blood samples were collected in sodium citrate and EDTA tubes, stored in shipping containers at 2-8 degrees celsius, and transported to the Functional Fluidics lab facility in Awka, Nigeria within 48hrs.

Functional Fluidics Nigeria-based laboratory team transferred patient data to the US-based team for analysis. FA-WB-VCAM, FA-WB-Psel, and LoRRCA results from samples collected from individuals with SCD recruited in the US and performed in the Detroit, MI facility were compared to FA-WB-VCAM, FA-WB-Psel, and LoRRCA results from samples collected from individuals with SCD recruited in Nigeria and performed in the Awka, Nigeria facility.

The Nigeria clinical site and specialty lab was able to address major challenges including cultural barriers, supply chain deficiencies and lack of patient education. To address cultural barriers, an on-site team, native to the existing culture and sensitive to the regional nuances was established. They collaborate effectively with our US-based team to ensure harmonization of standards and procedures. Supply chain gaps were addressed to enable time sensitive, temperature-controlled sample shipments with strict compliance with regulatory standards. Improvements in patient education and outcomes were initiated with established scientific and medical partnerships to engage regional Non-governmental Organizations (NGOs).

The comparative analysis between the US and Nigeria SCD populations showed significantly greater adhesive and reduced deformability properties in the Nigeria population.The median (range) of the adhesion value obtained for biomarkers in the US vs the Nigeria population were n=994, 284 (12-1313) cells/mm² (US) vs n=12, 560 (45-799) cells/mm²(Nigeria) for FA-WB-VCAM, 44 (2-487) cells/mm² (US) vs 35 (7-117)cells/mm² (Nigeria) for FA-WB-Psel. The data also showed reduced deformability properties with LoRRCA Oxygenscan (expressed as median with range) at EImin 0.12 (0.06-0.26) (US, n=8) and 0.03 (0.01-0.20) (Nigeria, n=6) and EImax- 0.45 (0.37-0.57) PoS- 33-49 mmHg (US) and EImax- 0.3-0.37, PoS- 49-57 mmHg (Nigeria)

Sub-saharan Africa has the highest global disease burden of SCD and has traditionally been underrepresented in clinical trials. More clinical trials in this region could accelerate clinical trial recruitment, and make innovative therapies more accessible. In this report, we demonstrate that a clinical site and RBC specialty lab established in Awka, Nigeria can adopt SOPs for proprietary flow adhesion assays and LoRRCA and demonstrate similar performance metrics. The ability to conduct high-complexity RBC function testing in Nigeria removes a major barrier to producing clinical trial data that can be compared broadly across multiple geographies. This could also have significant implications for comparing efficacy of SCD-modifying therapies across different geographies. Additional studies are underway to evaluate differences between US and Nigeria SCD populations.

White:Functional Fluidics: Other: contractor and shareholder in privately held company. Borhan:Funcitonal Fluidics: Current Employment.