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Gene therapymay
improve quality of life for
haemophilia patients
P
atients with haemophilia B, who are unable to
produce factor IX, began producing factor IX at
sufficient levels after receiving a single infusion of
the investigational gene therapy product SPK-9001, finds
preliminary data of an ongoing phase 1/2 trial.
Katherine A. High, MD, of Spark Therapeutics, Inc.
Philadelphia, Pennsylvania, explained that the standard of
care for haemophilia B requires patients to self-administer
intravenous infusions of laboratory-produced factor IX at
regular intervals, typically once to twice a week.
Factor IX levels fluctuate widely, and patients may need
to limit their activities to avoid breakthrough bleeding
when their factor IX levels are low.
The ongoing trial involves seven previously treated adult
patients with an extremely deficient, baseline factor IX
< 2%.
Twelve weeks after SPK-9001 infusion, patients showed
factor IX levels of 20–40%, and an overall average of
32%, sufficiently close to normal (at least 50% in healthy
adults). Maintaining a minimum level of 12% prevents
minor, chronic joint bleeding, a common cause of disa-
bility in patients with haemophilia.
SPK-9001 uses an inactive adenovirus vector that
delivers a small section of DNA that, when stabilised
in the patient’s hepatocytes, allows the body to produce
factor IX.
Factor IX levels achieved with SPK-9001 to date have
been sufficient to allow patients to engage in normal
daily activities without the need for factor IX infusions.
Though none of the seven participants have required in-
fusions of factor IX concentrates to prevent bleeding, one
precautionary infusion was needed due to a suspected
ankle bleed 2 days after administration of SPK-9001. In
addition, six patients reported increased physical activity
and improved quality of life.
Dr High said, “One of the potential innovations with gene
therapy for haemophilia B, compared to factor IX infu-
sions, is that once patients establish a stable factor activity
level, they may remain at that level for an extended time.
“At factor IX levels attained in the study, patients with
haemophilia do not have to worry about bleeding. Most
normal activities of daily living should be open to them.
The therapy could mean a potential paradigm shift in
the treatment of haemophilia.”
One participant suffered an autoimmune response and
needed corticosteroids. Despite the immune response
and decline in factor IX activity level, this patient has not
experienced any bleeds or required replacement factor IX.
Dr High concluded that the results show the highest and
most consistent levels of factor IX production of any gene
therapy tested to date. Dr High and colleagues plan to
continue to track patient outcomes for at least 5 years.
PracticeUpdate Editorial Team
Complete remissions with anti-CD22
CAR-T in childrenwith relapsed/
refractory ALL
C
hildren and young adults with
relapsed or refractory acute
lymphoblastic leukaemia who
received chimeric antigen receptor
(CAR) T cell therapy targeting the
CD22 protein on the leukocyte sur-
face, appeared to mount a clinical
response and in some cases achieved
remission. The early findings of a
phase 1 clinical trial were reported at
ASH 2016.
Terry J. Fry, MD, of the Center for
Cancer Research, National Cancer
Institute, Bethesda, Maryland, ex-
plained that a team from the Pediatric
Oncology Branch of the National Can-
cer Institute of the National Institutes
of Health genetically altered patients’
own T cells to track down and kill
cancer cells expressing CD22.
The study was the first to evaluate
this new target of immunotherapy in
humans, and provides a first glimpse
into how patients who already received
CAR-T therapy directed at a different
antigen, CD19, might fare when given
a second immunotherapy.
The first three patients treated at the
second dose level attained complete
remission with no evidence of residual
disease.
Based on these initial results, Dr Fry
and coinvestigators treated additional
patients (16 in total) and found that
eight of the 10 patients attained com-
plete remission when treated at the top
dose levels.
Dr Fry said, “We’ve been able to show
that you can give a second CAR-T
therapy directed against a different an-
tigen and it will be safe and effective.”
Dr Fry said the result adds to the notion
that a single antigen-directed CAR-T
immunotherapy probably won’t be
sufficient for long-term durable remis-
sions in many patients. It points to the
potential for bispecific targeting.
The trial included 16 patients with
relapsed or treatment-resistant acute
lymphoblastic leukaemia who were
either CAR-T naïve or previously
treated with anti-CD19 CAR-T cells
and/or blinatumomab therapy and had
relapsed with CD19-negative disease.
Patients ranged in age from 7–22 years
of age. All had CD22-positive acute
lymphoblastic leukaemia and had
previously undergone at least one al-
logeneic stem cell transplant.
The majority of treated patients had re-
lapsed after earlier anti-CD19 CAR-T
cell therapy before entering the trial.
Researchers then collected T cells
from eligible patients and modified
them to recognise and bind to CD22.
Patients then received an infusion of
these enhanced cells and were evalu-
ated for response and adverse effects
after an average of 28 days.
The trial is continuing to accrue pa-
tients, and these early results raise
new questions about how anti-CD22
CAR-T therapy might best be used.
For example, whether it is better to
wait for relapse after initial CAR-T
therapy, or to pre-empt relapse by
co-treating it.
Dr Fry and the team plan to investi-
gate combined use of anti-CD19 and
CD22 CAR-T targeting approaches
with the hypothesis that combined
therapy will raise the likelihood of
sustained remission.
PracticeUpdate Editorial Team
© ASH 2016
CONFERENCE COVERAGE
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PRACTICEUPDATE HAEMATOLOGY & ONCOLOGY