Gene Edited Cell Therapy Improves Fetal Hemoglobin Expression in Patients With Sickle Cell Disease
All evaluable treated participants experienced a reduction in vaso-occlusive events after treatment with ARU-1801.
ARU-1801, a modified γ-globin lentiviral gene-edited cell therapy, has demonstrated safety and efficacy in sickle cell disease (SCD), according to results from the phase 1/2 Momentum study (NCT02186418).1,2
Data from the study were presented at the 63rd Annual American Society of Hematology (ASH) Meeting, December 11-14, 2021, by Punam Malik, MD, director, Cincinnati Comprehensive Sickle Cell Center; program leader, Hematology and Gene Therapy Program; and Marjory J. Johnson Chair, Gene and Cell Therapy, Cincinnati Children’s Medical Hospital.1
"The emerging clinical data shows that ARU-1801 holds promise for achieving durable responses in patients with severe SCD using only reduced intensity conditioning—a key differentiator from other investigational gene therapy regimens," Malik, who is also professor, department of pediatrics, University of Cincinnati, said in a statement.2 "Given the advantage for patients, providers and payers a reduced conditioning regimen offers, ARU-1801 has the potential to be an important option for SCD patients seeking gene therapy, including those in low resource settings."
The open label, phase 1/2 Momentum study is investigating ARU-1801, which uses a modified γ-globin lentiviral vector to produce fetal hemoglobin (HbF)G16D within autologous CD34+ hematopoietic stem cells (HSCs), given with reduced intensity conditioning (RIC; melphalan). It is primarily assessing safety with outcomes measuring grade 3 allergic reaction, grade 4 and neutropenia, grade 3/4 organ toxicity, adverse events (AEs), serious AEs, death, hematologic malignancy or cancer, and neutrophil and platelet recovery, as well as measures relating to CD34+ cell collection and engraftment. Secondary outcome measures assess exploratory efficacy via biomarkers, engraftment, vaso-occlusive events (VOEs), and quality of life.
READ MORE: IND Accepted for Sickle Cell Disease Cell Therapy
Four patients (mean age, 26 years; range, 19-35) have been treated with ARU-1801 as of July 28, 2021, 3 of which were followed for at least 12 months. AEs included transient neutropenia and thrombocytopenia, which lasted a median 7 days each. No other serious AEs related to chemotherapy or ARU-1801 have been observed to date.
All patients have experienced stable HbF expression. At 36 months post-treatment, patient 1 had stable 27% HbF expression and 64% F-cells and patient 2 had stable 14% HbF and 37% F-cells (lower engraftment due to renal hyperfiltration during conditioning). SCD manifestations improved in these patients, with 93% and 85% fewer annualized VOEs in the 2 years post-treatment compared with pre-treatment.
Patient 3 had a stable 36% HbF at 15 months post-treatment with a modified and improved ARU-1801 as well as 96% F-cells (pancellular distribution). This patient has had no VOEs since treatment, a 100% reduction from baseline.
"Clinical data from our ongoing MOMENTUM study has shown 100% resolution of vaso-oclusive events (VOE) in our recently treated SCD patients at 18 and 12 months of follow up," Will Chou, MD, chief executive officer, Aruvant, added to the statement.2 "In addition, we are excited to be sharing additional clinical data at ASH that demonstrates how the unique anti-sickling potency of ARU-1801 translates to these robust clinical outcomes."
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