Gene therapy for Sickle cell disease

January 2022 Health Innovation Nalinee Pathak

Sickle cell disease is caused due to mutations in the beta-globin gene and is characterised by the recurrence of painful complications (vaso-occlusive events). A new gene therapy called LentiGlobin involves autologous transplantation of hematopoietic stem and progenitor cells transduced with a lentiviral vector encoding a modified beta-globin gene that produces antisickling haemoglobin, HbAT87Q.

Study design

In this ongoing phase 1/2 study, three patient groups (A, B and C) were established. The treatment process was optimised in the initial groups, i.e. A (n=7) and B (n=2). Group C was used to evaluate the efficacy of LentiGlobin, where patients who had a minimum of four severe vaso-occlusive events in the last two years were enrolled. An unprespecified interim analysis was performed for evaluating the efficacy and safety of Lentoglobin of Group C (n=35).

Main Findings

With a median follow up of 17.3 months (3.7-37.6), engraftment was observed in all 35 patients. Moreover, the median total haemoglobin (Hb) showed an increase from 8.5 g/deciliter to 11g or more/deciliter during six months to thirty-six months after infusion. HbAT87Q contributed to at least 40% of Hb, and it was well distributed  (85±8% ) across red cells. No severe vaso-occlusive events were observed in evaluated patients (n=25) in comparison to a median of 3.5 events/year before treatment. Non-serious adverse events were observed in three patients and were resolved within a week of onset. No instance of hematologic cancer was observed up to 37.6 months of follow up.

Conclusion

The results demonstrate the efficacy of gene therapy, LentiGlobin, in resolving severe vaso-occlusive events in sickle cell patients.

Reference

Kanter J, Walters MC, Krishnamurti L, et al. Biologic and Clinical Efficacy of LentiGlobin for Sickle Cell Disease. N Engl J Med. 2021;10.1056/NEJMoa2117175.

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