Biologic and Clinical Efficacy of LentiGlobin for Sickle Cell Disease
In unprespecified interim analysis of ongoing phase 1–2 study (n=35), single treatment with LentiGlobin resulted in sustained production of HbAT87Q in most red cells, leading to reduced haemolysis and complete resolution of severe vaso-occlusive events (3.5 events/year pre-study)
Source:
New England Journal of Medicine
SPS commentary:
Gene therapy with the use of LentiGlobin consists of autologous transplantation of hematopoietic stem and progenitor cells transduced with the BB305 lentiviral vector encoding a modified β-globin gene, which produces an antisickling hemoglobin, HbAT87Q.
In study, engraftment occurred in all 35 patients. The median total haemoglobin level increased from 8.5 g per deciliter at baseline to ≥11 g per deciliter from 6 months through 36 months after infusion. Three patients had a nonserious adverse event related or possibly related to LentiGlobin that resolved within 1 week after onset.
An editorial questions whether in the longer term, induction of high levels of antisickling haemoglobin, will prevent all disease complications and justify the rigors and expense of this procedure. It notes that allogeneic haematopoietic stem-cell transplantation from HLA-identical sibling donors is potentially curative, with more than 90% are treated by this procedure experiencing event-free survival, thoughh less than 20% of patients have a donor. It adds that gene therapy with autologous stem cells extends the possibility of a cure to all patients without the need for immunosuppression, but unfortunately, any highly efficacious gene-based treatment is unlikely to improve the health of most people with sickle cell disease, because the greatest burden of disease is in countries where access to highly technological health care is limited. It points out drugs that achieve even modest levels of foetal haemoglobin expression in most sickle erythrocytes have a higher likelihood of benefiting populations suffering the most from this disease