Emerging Cell-Based Gene Therapies in Sickle Cell Disease: A Systematic Review of Casgevy and Lyfgenia

Background: In 2023, the FDA approved two emerging cell-based gene therapies for the treatment of severe sickle cell disease (SCD): Casgevy and Lyfgenia. Casgevy utilizes the newer CRISPR/Cas9 technology, while Lyfgenia relies on a Lentiviral vector. These therapies consist of autologous hematopoietic stem cell transplantation, in which the cells are genetically modified before infusing them back into the body. The study aim was to conduct a thorough systematic review to determine an efficient choice between Casgevy and Lyfgenia by comparing their ability to increase anti-sickling hemoglobin and eliminate vaso-occlusive crises (VOCs), factoring in the adverse effects caused by each process. Methods and Results: This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) guidelines. Ten articles were analyzed and compared after searching PubMed and Google Scholar databases. Both therapy strategies were equally efficient in eliminating VOC and had similar effects on anti-sickling hemoglobin fractions. Their adverse effects are also similar and are related to the chemotherapy shared between autologous and allogenic transplants and not the gene therapies themselves, barring the occurrence of acute myeloid leukemia in 2 patients receiving the unmodified version of Lyfgenia. Conclusion: Casgevy and Lyfgenia are equally effective in their functions, although Casgevy appears to be the safer choice. However, the lack of follow-up for the patients in either gene therapy's respective trials leads to a lack of confidence in firm declarations.