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Featured research from recent issues of Blood
PAPER SPOTLIGHT
A New Treatment Option
for Patients with Severe
von Willebrand Disease?
Treatment options to limit
the risk of life-threatening
bleeds associated with
severe von Willebrand
disease (vWD), a condition
caused by a deficiency
in or impairment of the
blood-clotting protein von
Willebrand factor (vWF),
are limited, but a study
published in Blood shows
safe and promising results
with a new recombinant
vWF product.
Effective treatment
requires correction of the
dual defect of hemostasis
associated with vWD, Joan
C. Gill, MD, of the Blood
Center of Wisconsin and
Medical College of Wisconsin in Milwaukee, and
colleagues explained, including abnormal platelet
adhesion and aggregation
and defective secondary
TABLE 1.
hemostasis. In the phase
III, prospective, randomized, single-blind, crossover trial, they evaluated
the safety and efficacy
of recombinant (r)vWF.
Human vWF produced by
recombinant technology
has the potential of overcoming the limitations
associated with plasmaderived vWF concentrates
– including the theoretical
risk of pathogen transmission, limits of plasma
donor availability, and the
varying composition of
the source plasma.
“[This] represents the
most significant advancement for the treatment of
people living with vWD in
two decades,” Dr. Gill told
ASH Clinical News. “[This
treatment] is specifically
designed to be a pure vWF
product without factor VIII
(FVIII), allowing physicians
and patients to dose vWF
and FVIII independently to
the precise levels needed,
based on the individual
patients’ requirements
and disease type, while
avoiding the risk of FVIII
accumulation.”
Patients 18 to 65 years
old with type 3 or severe
type 1 and type 2A, type
2B, type 2N, type 2M, or
type 3 vWD were included
in this phase III trial.
Patients were excluded
if they had a history of
vWF or FVIII inhibitors,
immunologic disorders, or
thromboembolic events.
A total of 49 patients, all
of whom had been treated
for at least one bleed with
a vWF concentrate within
12 months prior to enroll-
ment, were evaluated.
Bleeding episodes were
to be treated with an initial
infusion of 40 to 60 IU/kg
rvWF for minor to moderate bleeds (such as epistaxis, oral bleeding, and
menorrhagia), and up to
80 IU/kg for major bleeds
(including severe or refractory epistaxis or menorrhagia, gastrointestinal
bleeding, central nervous
system trauma, hemarthrosis, or post-traumatic
hemorrhage). The initial
dose of rvWF was administered together with rFVIII
and subsequently alone,
so long as hemostatic FVIII
concentrate levels were
maintained. Treatment of
each bleed was rated by a
predefined four-point scale
based on the number of
rvWF infusions administered to control the bleed
versus the treating physician’s estimated number
of infusions required.
Subjects were enrolled
into one of four treatment
arms:
• 50 IU/kg rvWF:rFVIII
or rvWF:placebo
(crossover) only
Treatment Summary of Bleeding Episodes
Number
of
bleeding
episodes
Total
number
of
infusions
Median number
of infusions/
bleeds (range)
Median rvWF
dose (IU/kg)
per infusion
Median rFVIII
dose (IU/kg) per
infusion
Percentage of
bleeds (n=192)
ratings
(excellent/good)
Type 3
175
219
1
(1-4)
48.2
(range, 23.8-184.9)
33.6
(range, 16.6-129.3)
100%
(171/4)
Type 2A
16
18
1
(1-2)
50.2
(range, 32.9-90.2)
32.5
(range, 23.7-38.6)
100%
(14/2)
Type 2N
1
1
1
(1-1)
54.3
(range, 54.3-54.3)
N/A
100%
(1/0)
Minor
122
132
1
(1-3)
43.3
(range, 25.2-158.2)
33.5
(range, 17.6-86.2)
100%
(119/3)
Moderate
61
89
1
(1-4)
52.7
(range, 23.8-184.9)
36.9
(range, 16.6-129.3)
100%
(59/2)
Major/
Severe
7
15
2
(1-3)
100.0
(range, 57.5-135.0)
39.0
(range, 25.0-42.3)
100%
(6/1)
Unknown
2
2
1
(1-1)
33.4
(range, 33.1-33.8)
23.3
(range, 23.1-23.6)
100%
(2/0)
vWD Type
Bleed Severity
26
ASH Clinical News
• 50 IU/kg rvWF:rFVIII or
rvWF:placebo (crossover), followed by 12
months of on-demand
bleed treatment
• 80 IU/kg rvWF repeated after 6 months
(for pharmacokinetic
assessment), followed by 6 months
of on-demand bleed
treatment
• On-demand treatment of bleeding episodes for 12 months
To determine the extent
of bleeding control
(the study’s primary
endpoint), investigators rated hemostatic
efficacy on a scale of 1 to
4 (excellent=1, none=4),
with a lower score indicating fewer treatment
infusions were needed
to control the bleed.
Secondary endpoints
included the number of
treated bleeding episodes
with a hemostatic efficacy rating of excellent
or good, and the number
of infusions and units of
rvWF/rFVIII or rvWF to
control a bleed.
A total of 49 patients were enrolled and
assessed for eligibility,
and 37 patients (median age=37 years) were
exposed to rvWF during
the study, of whom 22
experienced at least one
bleeding episode that was
treated with rvWF.
A total of 192 bleeding episodes treated with
rvWF were assessed for
hemostatic efficacy:
• 122 minor
• 61 moderate
• 7 major/severe
• 2 unknown severity
August 2015