Genetics

1. Biologic and
Clinical Efficacy
of LentiGlobin
for Sickle Cell
Disease
Journal Article on
Recent Advances in
Genetics

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Background
Sickle cell disease is characterized
by the painful recurrence of vaso-
occlusive events. Gene therapy with
the use of LentiGlobin for sickle cell
disease (bb1111:lovotibeglolene
autotemcel)consist of autologous
transplantation of hematopoietic
stem and progenitor cells
transduced with the BB305 lentiviral
vector encoding a modified B-globin
gene, which produces an
antisickling hemoglobin, HbAT87Q
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Sickle Cell
Single point mutation in the gene
encoding B-globin (HBB)
Patients with sickle cell disease may suffer
Vas0-occlusive events
Progressive vasculopathy
Chronic Hemolytic Anemia

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Treatment for Sickle Cell Anemia
 HLA-matched sibling allogenic
hematopoietic treatment

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LENTIGLOBIN
 A gene therapy consist of the
autologous transplantation of
hematopoietic stem and progenitor
cells (HSPCs) transduced with the
BB305 lentiviral vector coding for a
modified B-globin gene

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 As the modified B-globin gene is
produced, it resulted to the production
of an antisickling hemoglobin, HbAT87Q
 HbAT87Q is a modified adult hemoglobin
with an amino acid substitution
(threonine to glutamine at position 87)

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TRIAL DESIGN AND OVERSIGHT
• This is nonrandomized and single-dose
cilinical trial conducted at 11 sites across
United States in collaboration with the
Bluebird Bio

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ENTRY CRITERIA AND PATIENT
POPULATION
• Eligible patient were between 12 to 50 years
of age, had received diagnosis of sickle cell
disease
• 24 month history of active treatment of
sickle cell disease
• No opportunity for matched HLA-identical
hematopoietic-cell donation.

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TRIAL PROCEDURES
• Precollection preparation
• Collection through plerixafor mobilization
and apheresis
• Refined LentiGlobin manufacturing process
through the ex vivo transduction of HSPC
with the BB305 letiviral vector

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Conclusion
 Sickle cell disease is a lifelong, genetic disorder and the effect
of one-time gene therapy requires a long time evaluation.
 It remains to be determined whether the effects of
LentiGlobin gene therapy are lifelong, as anticipated on the
basis of durability in clinical and precilinical studies and in
studies of allogenic hematopoietic stem cell transplantation.