CLINICAL NEWS
Monahan and colleagues tested the safety
and pharmacokinetics of the experimental therapy in humans, with the goal of
determining the dose required to achieve
stable plasma Factor IX activity without
triggering an immune response. Inclusion
criteria were: men 18 to 75 years old with
established hemophilia B who had more
than three hemorrhages per year requiring
treatment with Factor IX, plasma Factor IX
activity ≤2 percent, and a negative screen
for hepatitis C.
At the time of the study presentation,
seven patients have been treated with
BAX335 in three dosing cohorts, with
follow-up ranging from seven weeks to two
years:
• Cohort 1: 2 x 1011 vg kg-1 (2 patients)
• Cohort 2: 1 x 1012 vg kg-1 (3 patients)
• Cohort 3: 3 x 1012 vg kg-1 (2 patients)
BAX335 was administered in a single
intravenous dose with up to four sequentially ascending doses. Pharmacodynamic
(plasma FIX activity) and safety data (immune response, adverse events [AEs]) were
collected.
In the lowest-dose cohort, patients
achieved therapeutic Factor IX levels of 3
percent. Factor IX activity was greater in
the middle-dosing cohort, with subjects
sustaining Factor IX levels of 0.5 to 20
percent observed at six months postdosing – one of whom sustained a stable
plasma Factor IX activity between 20 to 25
percent at 52 weeks after treatment. Two of
the three study subjects in this cohort also
remained free of spontaneous hemorrhage
without the need for regular FIX infusions.
There were, however, setbacks in the
highest-dosing cohort: Although the two
subjects achieved expression levels above
40 percent, both experienced an immune
response that led to decreased FIX expression. One patient returned to regular FIX
infusions.
Importantly, though, no patients
developed FIX inhibitors against BAX335.
The researchers noted that no severe
treatment-related AEs have been observed in this small cohort at this time
– apart from the two incidents of immune
response to treatment. In the future, the
trial will enroll up to 16 male adults with
severe hemophilia B.
According to Dr. Monahan, these preliminary findings “underscore the difficulty
of thinking that we can easily interrupt an
immune response once the process has
begun but, thankfully, there have been no
inhibitors observed against FIX or against
the variant used in this vector.” ●
REFERENCE
Monahan PE, Walsh CE, Powell J. Update on a phase 1/2 open-label
trial of BAX335, an adeno-associated virus 8 (AAV8) vector-based gene
therapy program for hemophilia B. Abstract #LB101. Presented at the
International Society on Thrombosis and Haemostasis 2015 Congress,
June 24, 2015, Toronto, Canada.
ASHClinicalNews.org
For Occult Cancer in VTE
Patients, Routine Screening
Is Enough
For the more than 500,000
Americans and Canadians
who are diagnosed with
unprovoked venous thromboembolism (VTE) each year,
VTE may be an early sign of
cancer. Despite this, there are
no standard practices regarding how aggressively physicians screen for occult cancer
among VTE patients.
In a study presented at
the International Society on
Thrombosis and Haemostasis
(ISTH) Congress, Marc Carrier, MD, MSc, reported that
the prevalence of occult cancer was low among patients
with a first unprovoked VTE
and that routine, comprehensive screening with computed
tomography (CT) offered no
additional detection benefit than a limited screening
method.
“It has been described that
up to 10 percent of patients
with unprovoked VTE are
diagnosed with cancer in
the year following their VTE
diagnosis,” Dr. Carrier, of
the University of Ottawa,
said during his presentation.
“Therefore, it’s appealing for
clinicians to screen these patients for occult cancer, but it
has led to a lot of great diversity in practices.” For instance,
some clinicians prefer to use
a limited screening strategy
(a history, physical examination, routine blood tests, and
a chest X-ray), while others
prefer to use additional tests
(i.e., CT scans or ultrasound).
In the multicenter, openlabel, randomized, controlled
SOME (Screening for Occult
Malignancy in Patients with
Idiopathic Venous Thromboembolism) trial that Dr.
Carrier reported on during
the meeting, investigators assessed the efficacy of a screening strategy for occult cancer,
which included comprehensive CT of the abdomen and
pelvis in patients who had a
first unprovoked VTE. The
study’s findings were simultaneously published in The New
England Journal of Medicine.
Eight-hundred and fiftyfour patients were enrolled
from nine Canadian centers.
Patients were randomized to
undergo conventional limited
occult-cancer screening (i.e.,
basic blood tests, chest radiography, and screening for
breast, cervical, and prostate
Marc Carrier, MD, MSc
cancer; n=431) or limited
occult-cancer screening with
“The risk of occult cancer in
The low incidence of occombination CT screening
patients with unprovoked or
cult cancers is “reassuring for
(i.e., virtual colonoscopy
idiopathic VTE was lower
clinicians and patients,” Dr.
and gastroscopy, biphasic
than expected,” Dr. CarC