Living with Recurrent Vaso-Occlusive Crises: A Case Report of Gene Therapy for Sickle Cell Disease and a Review of What Curative Intent Changes for Patients and Families

For most of the history of sickle cell disease, treatment meant reducing the frequency of crises rather than ending them. Gene
therapy offers something the field has not previously had to describe to patients: the prospect of a life without vaso-occlusive
crises at all.
Objectives: To review the published evidence on gene therapy for severe sickle cell disease: what the trials achieved, on how
many patients and over what period, what the treatment requires of the person receiving it, and what remains unknown at the
point of licensing.
Material and Methods: Narrative review of phase 1 to 3 trials, natural history studies, guideline documents and health-economic
analyses indexed in PubMed and the major haematology journals. No new patient data were generated; every estimate quoted is
one published by the original investigators.
Results: In the pivotal phase 3 study, 44 patients aged 12 to 35 with at least two severe vaso-occlusive crises in each of the two
preceding years received exagamglogene autotemcel. Of the 30 with sufficient follow-up, 29 (97 per cent, 95% CI 83 to 100) were
free of severe vaso-occlusive crises for at least 12 consecutive months, and all 30 (100 per cent, 95% CI 88 to 100) were free of
hospitalisation for one. Median follow-up was 19.3 months (range 0.8 to 48.1). The safety profile was consistent with
myeloablative busulfan conditioning, and no cancers occurred.
Conclusion: The effect size is as large as any in haematology, and the evidence base is thirty patients followed for a median of
nineteen months. Both statements are true and both belong in the conversation, alongside the cost of the treatment itself:
myeloablative conditioning, probable infertility, weeks in hospital, and a price that places it out of reach of most of the world's
patients.
Abbreviations: exa-cel – Exagamglogene Autotemcel, HbF – Fetal Haemoglobin, HSCT – Haematopoietic Stem Cell
Transplantation, HSPC – Haematopoietic Stem and Progenitor Cell, SCD – Sickle Cell Disease, VOC – Vaso-Occlusive Crisis,
CI – Confidence Interval.