{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:39:39Z","timestamp":1791261579710,"version":"4.1.0"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T00:00:00Z","timestamp":1765152000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["ebm-journal.org"],"crossmark-restriction":true},"short-container-title":["Exp. Biol. Med."],"abstract":"<jats:p>\n                    Sickle cell disease (SCD) is a severe inherited hemoglobinopathy with limited curative treatment options. In December 2023, the U.S. FDA approved two autologous gene therapies, lovo-cel (bluebird bio) and exa-cel (Vertex\/CRISPR Therapeutics), offering potentially transformative outcomes. We performed a comparative analysis of these therapies based on published clinical trial design, patient eligibility, manufacturing requirements, and reported efficacy and safety outcomes. Overall, participants treated with lovo-cel had more severe baseline disease, reflected by a higher median rate of vaso-occlusive events (VOEs), despite the use of a more stringent VOE definition. Mobilization of hematopoietic stem cells (HSCs) with single-agent plerixafor proved challenging in both trials, with most participants requiring multiple mobilization and apheresis cycles. A greater proportion of exa-cel participants required three or more apheresis procedures, driven by higher CD34\n                    <jats:sup>+<\/jats:sup>\n                    cell dose targets needed to compensate for CRISPR-associated HSC loss. Both therapies demonstrated greater than 90% resolution of severe VOEs, with near-complete resolution in pediatric participants. A small subset of participants experienced VOEs post-treatment, including events occurring beyond the primary efficacy assessment period. Notably, no recurrent strokes were reported among lovo-cel treated participants with a history of overt stroke. Both therapies provide durable, clinically meaningful benefit and represent a major advancement in SCD management. However, differences in trial populations, cell collection logistics, and manufacturing have important implications for real-world applications. Continued long-term follow-up and the establishment of standardized post-treatment registries will be critical to fully assess durability, monitor late effects, and inform patient selection.\n                  <\/jats:p>","DOI":"10.3389\/ebm.2025.10806","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T07:00:23Z","timestamp":1765177223000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Clinical data comparison for FDA-approved gene therapies in sickle cell disease"],"prefix":"10.3389","volume":"250","author":[{"given":"Alexis","family":"Leonard","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Kanter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e585","DOI":"10.1016\/s2352-3026(23)00118-7","article-title":"Global, regional, and national prevalence and mortality burden of sickle cell disease, 2000-2021: a systematic analysis from the global burden of disease study 2021","volume":"10","year":"2023","journal-title":"The Lancet Haematol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1056\/nejmoa1715971","article-title":"A phase 3 trial of l-Glutamine in sickle cell disease","volume":"379","author":"Niihara","year":"2018","journal-title":"N Engl J 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