GLOBE1 βAS3 Modified Autologous CD34+ Cells (Drepaglobe) / Public Assistance - Paris Hospitals - LARVOL DELTA

Severe inflammation and lineage skewing are associated with poor engraftment of engineered hematopoietic stem cells in patients with sickle cell disease (ESGCT 2024) - P1/2 | "A Phase I/II clinical trial based on the DREPAGLOBE lentiviral vector, driving erythroid-specific expression of an anti-sickling globin, has been conducted at the Necker hospital (NCT03964792)...To gain insights into factors that may explain the variable levels of engraftment of gene-corrected cells in the 4 patients, we performed a transcriptomic analysis of plerixafor-mobilized HSPC from the treated SCD patients or healthy donors (HD)...In addition, the identification of predictive biomarkers would allow HSCs to be screened using targeted RNA sequencing. This could allow stratification of patients with a low inflammatory signature score (who could be treated safely with GT) from those with a high inflammatory signature score (who could be pretreated with anti-inflammatory drugs)."

Clinical • Gene Therapies • Genetic Disorders • Hematological Disorders • Inflammation • Sickle Cell Disease • HBB • ITGA2B • TFRC

Severe inflammation and lineage skewing are associated with poor engraftment of engineered hematopoietic stem cells in patients with sickle cell disease. (PubMed, Nat Commun) - P1/2 | "We completed a Phase I/II open-label clinical trial (NCT03964792) for patients with SCD using a lentiviral vector (DREPAGLOBE) expressing a potent anti-sickling β-globin...However, its efficacy is variable and probably depends on the number of infused HSCs and intrinsic, engraftment-impairing inflammatory alterations in HSCs. Trial: NCT03964792."

Journal • Gene Therapies • Genetic Disorders • Hematological Disorders • Inflammation • Sickle Cell Disease • Transplantation • TNFA

Clinical Results of the Drepaglobe Trial for Sickle Cell Disease Patients (ASH 2021) - P1/2 | "In vitro and in vivo preclinical studies demonstrated the safety and efficacy of a gene therapy (GT) protocol based on the efficient transduction of plerixafor-mobilized SCD HSPCs by βAS3 LV...Despite the rapid resolution of these episodes, P1 started hydroxyurea at month 10 and stopped it at month 16...Overall, these clinical data indicate a variable efficacy of the DREPAGLOBE GT treatment, which likely depends on the extent of gene marking achieved in HSCs in vivo and on the engraftment capability of genetically modified HSCs in SCD patients’ bone marrow. Single-cell RNA-seq analysis of HSPCs and evaluation of the bone marrow niche in SCD patients will aid to define critical parameters for achieving successful outcomes in GT clinical trials for SCD."

Clinical • Gene Therapies • Genetic Disorders • Hematological Disorders • Immunology • Inflammation • Sickle Cell Disease • Transplantation • HPX

Safety and Efficacy of Gene Therapy of the Sickle Cell Disease by Transplantation of an Autologous CD34+ Enriched Cell Fraction That Contains CD34+ Cells Transduced ex Vivo With the GLOBE1 Lentiviral Vector Expressing the βAS3 Globin Gene in Patients With Sickle Cell Disease (DREPAGLOBE) (clinicaltrials.gov) - P1/2 | N=6 | Active, not recruiting | Sponsor: Assistance Publique - Hôpitaux de Paris | Recruiting ➔ Active, not recruiting | N=10 ➔ 6 | Trial completion date: Nov 2024 ➔ Jan 2024 | Trial primary completion date: Feb 2022 ➔ Jul 2022

Enrollment change • Enrollment closed • Preclinical • Trial completion date • Trial primary completion date • Gene Therapies • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • Transplantation

Safety and Efficacy of Gene Therapy of the Sickle Cell Disease by Transplantation of an Autologous CD34+ Enriched Cell Fraction That Contains CD34+ Cells Transduced ex Vivo With the GLOBE1 Lentiviral Vector Expressing the βAS3 Globin Gene in Patients With Sickle Cell Disease (DREPAGLOBE) (clinicaltrials.gov) - P1/2; N=10; Recruiting; Sponsor: Assistance Publique - Hôpitaux de Paris; Not yet recruiting ➔ Recruiting

Enrollment open • Gene Therapies • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • Transplantation