Innovative Curative Treatment of Beta Thalassemia: Cost-Efficacy Analysis of Gene Therapy Versus Allogenic Hematopoietic Stem-Cell Transplantation

Abstract

Seventy-five percent of patients with beta thalassemia (b-thalassemia) do not have human leukocyte antigen-matched siblings and until recently had no access to a curative treatment. Gene therapy is a promising treatment that can be proposed to these patients. This study estimates its cost and efficacy. In a monocentric retrospective study and cost-efficacy analysis, this study compared the two-year outcomes and costs of patients with b-thalassemia treated by gene therapy and hematopoietic stem-cell transplantation (HSCT). Grade III and grade IV complications, hospitalizations, and length of stay were extracted from the hospital discharge data. Costs were estimated from hospital accounting information and national cost studies. A total of seven patients with b-thalassemia treated between 2009 and 2016 were included, of whom four received gene therapy. Patients treated by gene therapy were older and had fewer complications and hospital admissions. Infectious complications were three times more frequent for patients treated with HSCT than for gene therapy. Average costs were e608,086 for patients treated by gene therapy and e215,571 for HSCT. The total cost of the vector was 48% of the total cost of gene therapy. Gene therapy as a curative alternative for patients lacking human leukocyte antigen-matched donors was costlier but resulted in fewer complications than HSCT.

Editing a γ-globin repressor binding site restores fetal hemoglobin synthesis and corrects the sickle cell disease phenotype

“…The same strategy could be beneficial also in the case of -thalassemia, potentially providing a more economical gene therapy approach compared to the use of LV vectors to deliver a functional -globin gene. LV manufacturing is complex and very expensive (44). Our genome editing approach requires the delivery of RNA/protein reagents that might be less expensive than LV production and thus would allow the broader use of gene therapy for -hemoglobinopathies.…”

In-Vivo Gene Therapy with Foamy Virus Vectors

“…Altogether, we have so far treated nine dogs (five with EF1α-EGFP-2A-γC; two with both EF1α-EGFP-2A-γC and PGK-mCherry-2A-γC and two dogs with PGK-mCherry-2A-γC and G-CSF/AMD3100 mobilization) [5,6] and all treated dogs demonstrated efficacy and safety of FVV in-vivo gene therapy in canine model. Out of nine treated SCID-X1 dogs, five lived more than a year and three lived for over 2.5 years.…”

“…Therapies based on gene transfer to hematopoietic stem and progenitor cells (HSPCs) have achieved tremendous curative outcomes over the past decade and due to revolutionary success in some of these gene therapy clinical trials, these outcomes will redefine the clinical management of patients [1][2][3]. Pioneering gene therapy trials have shown that the genetic engineering of HSPCs can be a potentially superior alternative to allogeneic transplantation in the treatment of hematological monogenetic disorders including primary immunodeficiencies [4][5][6]. Transfer of therapeutic genes into long-term repopulating HSPCs can potentially cure blood disorders such as hemoglobinopathies and primary immunodeficiencies.…”

Preimplantation Genetic Testing for HLA-matching: An Overview of Clinical Application and Utility

“…With more than one sibling the chances will increase (e.g., 43.7% with two siblings), overall, only 30% of patients are able to find an HLA identical match within their family [28]. Indeed, 75% of betathalassemia patients do not have HLA matched siblings [29]. In the absence of a matched sibling, a matched unrelated donor may be identified in national or international registries.…”

“…The safety and efficacy of gene therapy have already been investigated for different pathologies such as β-thalassemia, sickle-cell disease, severe combined immunodeficiency, Wiskott-Aldrich syndrome, muscular dystrophy, and chronic granulomatous disease. However, a recent cost-efficacy analysis of gene therapy versus HSCT for β-thalassemia concluded that the preparation and procedure costs are currently higher for gene therapy [29]. Additionally, a longer follow-up is required so that, as anticipated, the longterm health benefits of gene therapy become evident.…”