On Location 2015 ASH Annual Meeting
Lentiviral Gene Therapy:
A Major Win for Patients With Beta-Thalassemia Major?
Lentiviral vector gene therapy via autologous hematopoietic cell transplantation (AHCT)
with a median peak level of 5.4 g/dL (range = 2.4-8.9 g/dL) at three or more months
reduced transfusion needs and even led to transfusion independence in patients with
post-infusion.
β-thalassemia major, according to updated results from the Northstar Study, an open-label,
Among the seven subjects who were monitored for at least six months post-infusion,
multicenter, phase I/II study.
median HbAT87Q production was 5.2 g/dL (range = 1.9-8.2 g/dL). At the last follow-up
Lead investigator Mark C. Walters, MD, from the University of California, San
visit, total Hb ranged from 8.5 to 11.1 g/dL.
Francisco Benioff Children’s Hospital in Oakland, California, presented updated results
Prior to infusion, patients had received a median of 170 mL/kg per year of red blood
from the Northstar Study at this
year’s ASH annual meeting, saying
that, although this was a small study
with short-term follow-up, the results
are “promising.”
In the Northstar Study, researchers used a lentiviral vector to transport a functioning hemoglobin (Hb)
gene (an engineered ßA-T87Q-globin
gene, known as LentiGlobin BB305
Drug Product) into patients’ hematopoietic stem cells and then transfused
them back into the patients. Earli er
1,2
results indicated that patients with
ß-thalassemia major who underwent AHCT with the lentiviral drug
15.2 times fewer bleeding episodes with prophylaxis
product experienced improved
vs on-demand treatment (95% CI:27.2; P<0.0001)1*
ßA-T87Q-globin production, potentially
leading to transfusion independence.
While the study is ongoing, reMedian annual bleed rate (ABR)1,2
sults from the first 10 treated patients
(P<0.0001)
(median age = 26 years; range = 1835 years) with transfusion-dependent
Prophylaxis (n=42)
On-demand (n=42)
β-thalassemia major have been
52% (22 out of 42)
presented:
Kogenate® FS, antihemophilic factor (recombinant):
Proven bleed reduction in previously treated
adolescents and adults (ages 15 to 50)
with prophylaxis vs on demand
• Five with β0/β0 genotype
• Three with β0/βE genotype
• One with heterozygous β0
ASH Clinical News
Range: 0-104.1
Range: 0-19.8
Adults infusing with Kogenate FS experienced an average of 2 bleeds annually, compared
with those infusing on demand, who experienced 37 bleeds annually (P<0.0001 using ANOVA).1,2
genotype
42
Bleeds per year
P<0.0001 using analysis of variance (ANOVA).
• One with β0/β+ genotype
All of the patients included in the
study had undergone myeloablation
with busulfan prior to infusion with
the lentiviral drug product.
Patients were monitored for hematologic recovery, vector copy number, ßA-T87Q-globin expression, adverse
events, and transfusion requirements
after drug product infusion. Safety
was monitored through integration
site analysis and replication-competent lentivirus assays.
Patients received a median of 7.9
x 106 CD34+ cells/kg, and engraftment was seen in all of the patients
after infusion; median time to
engraftment was 17 days for neutrophils (range = 13-29) and 30 days for
platelets (range = 17-35).
“All of the subjects treated in
the study had a clinical benefit,
which was most pronounced in the
patients with non-β0/β0 genotypes,”
Dr. Walters said. All subjects had
detectable vector-derived HbAT87Q,
Bleeds per year
of prophylaxis patients
experienced 0 bleeds
per year.1
■
Prophylaxis reduced bleeds regardless of patient age, bleeding history, and absence or presence
of target joints1
*P<0.0001 using negative binomial model
INDICATIONS
Kogenate® FS antihemophilic factor (recombinant) is a recombinant factor VIII indicated for:
■ Control and prevention of bleeding episodes in adults and children with hemophilia A.
■ Surgical prophylaxis in adults and children with hemophilia A.
■ Routine prophylactic treatment to prevent or reduce the frequency of bleeding episodes
in children with hemophilia A and to reduce the risk of joint damage in children without
pre-existing joint damage.
■ Routine prophylactic treatment to prevent or reduce the frequency of bleeding episodes
in adults with hemophilia A.
■ Kogenate FS is not indicated for the treatment of von Willebrand disease.
■
SELECTED IMPORTANT SAFETY INFORMATION
■
Kogenate FS antihemophilic factor (recombinant) is contraindicated in patients who have
life-threatening hypersensitivity reactions, including anaphylaxis to mouse or hamster protein
or other constituents of the product.
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