Efficacy of Hypoxic Red Blood Cells Processed with the Hemanext ONE® System in Patients with Sickle Cell Anemia

/Abstract Sickle cell anemia (SCA) is one of a group of inherited red blood cell (RBC) disorders known as sickle cell disease (SCD). The disease is caused by a single point mutation that results in abnormal hemoglobin (Hb), also known as sickle hemoglobin (HbS). Two types of hemoglobin abnormalities cause the most severe SCA - HbSS and hemoglobin beta zero thalassemia (Hb S/β0). A type of blood transfusion therapy, known as red cell exchange (RCE) therapy, is used to improve anemia by decreasing the proportion of HbS relative to normal hemoglobin (HbA), thereby increasing oxygen (O2)-carrying capacity to alleviate symptoms and prevent complications. However, conventional transfusion methods come with inherent risks such as iron overload and alloimmunization, highlighting the need for alternative strategies. Despite several new therapies that have been developed over the past few years, including pharmacologic and gene therapy, they are not available or tolerable to all patients. These anemic patients continue to require RBC transfusions. Chronically transfused SCA patients are the most highly vulnerable of the “vulnerable populations” because they are entirely dependent on regular, high-quality blood products to remain healthy, and for those patients, blood transfusion therapy is the only viable option for survival. Hypoxic red blood cell (HRBC) transfusions have emerged as a promising approach to potentially improve treatment outcomes in SCA patients. Hemanext’s research has confirmed that storage of RBCs at low Hb O2 saturation (SO2) levels maintains more viable cells during storage and preserves the cells in a more physiologically optimal state by reducing oxidative damage and enhancing cell metabolism. This trial aims to rigorously assess, for the first time, the efficacy of HRBC transfusions compared to conventional RBC (CRBC) transfusions. By employing a multi-center, randomized, cross-over design, the trial will enroll 48 SCA patients across five United States (US) academic medical centers. The primary objective will evaluate the efficacy of HRBCs by measuring the rate of decline in %HbA and assessing its impact on reducing transfusion burden and, hence, transfusion-related outcomes including a comprehensive array of clinical and laboratory parameters and quality of life assessments. Patients will be randomized to receive either hypoxic or conventional RBC transfusions for six months. This will be followed by a "washout" phase and subsequent cross-over to the alternate treatment arm for another six months. Statistical analyses will employ robust methods to compare treatment effects. Demonstrated efficacy of HRBC transfusions could lead to a paradigm shift in transfusion therapy, potentially reducing complications and healthcare costs while improving patient outcomes. The long-term implications of this research extend beyond the realm of SCA to benefit patients with various hematological and acquired bleeding disorders and advance healthcare practices globally. Project Number: 1R44HL178006-01A1 | Fiscal Year: 2025 | NIH Institute/Center: National Heart Lung and Blood Institute (NHLBI) | Principal Investigator: Laurel Omert (+2 co-PIs) | Institution: NEW HEALTH SCIENCES, INC., Lexington, MA | Award Amount: $1,017,232 | Activity Code: R44 | Study Section: Special Emphasis Panel[ZHL1 CSR-D (M1)] View on NIH RePORTER: https://reporter.nih.gov/project-details/1R44HL17800601A1