CLINICAL NEWS
Emicizumab Prophylaxis Reduces
Bleeding Events in Hemophilia A
Without Inhibitors
Treatment with emicizumab was associated with
lower bleeding rates, compared with no prophy-
laxis, in patients with hemophilia A without in-
hibitors, according to findings from the phase III,
open-label HAVEN 3 study published in the New
England Journal of Medicine. Emicizumab also is
administered via subcutaneous injection, making
it a less burdensome alternative to regular prophy-
lactic intravenous infusions of factor VIII (FVIII),
the study’s lead author, Johnny Mahlangu,
MBBCh, MMed, of the University of the
Witwatersrand and National Health Laboratory
Service in Johannesburg, South Africa, told ASH
Clinical News.
“Subcutaneous injection of emicizumab every
week or two weeks results in better compliance
with prophylaxis, which is the current standard
of care,” he said, “and the reduction in bleed
rates will reduce the arthropathy associated with
hemophilia.”
Emicizumab is a recombinant, humanized,
bispecific monoclonal antibody that bridges acti-
vated factor IX and factor X to restore the function
of activated FVIII. Once-weekly emicizumab has
been proven effective for patients with hemophilia
A and inhibitors, but in this analysis, investigators
evaluated its safety and efficacy in patients ≥12
years of age without inhibitors who were undergo-
ing episodic or prophylactic FVIII infusions.
A total of 152 patients (age range = 14.4-50.6
years) were enrolled and randomized to one of
three treatment arms:
• group A: emicizumab 1.5 mg/kg once weekly
(n=36)
• group B: emicizumab 3.0 mg/kg every two
weeks (n=35)
• group C: no prophylaxis with an option to
receive emicizumab every two weeks after
≥24 weeks (n=18)
In groups A and B, patients received four initial
loading doses of emicizumab at 3.0 mg/kg per week.
An additional group, D, was reserved for 48
participants unable to join the other arms because
they were receiving adequate prophylactic FVIII
at the time of enrollment; these patients were
assigned to receive once-weekly emicizumab as
maintenance and could continue FVIII prophy-
laxis until the second loading dose of emicizumab.
In the instances of breakthrough bleeding
events, investigators administered additional
FVIII. Patients reported bleeding events, as well
as the administration of treatment throughout the
study, using an electronic handheld device.
The annualized bleeding rates among each
group were:
• group A: 1.5 events (range = 0.9-2.5 events)
• group B: 1.3 events (range = 0.8-2.3 events)
• group C: 38.2 events (range = 22.9-63.8
events)
Compared with no prophylaxis, therefore,
emicizumab prophylaxis significantly lowered
bleeding rates ( TABLE 2 ). Participants in the
once-weekly group were 96 percent less likely to
experience a bleeding event (rate ratio [RR] =
0.04; 95% CI 0.02-0.08; p<0.001) and participants
in the biweekly group were 97 percent less likely
(RR=0.03; 95% CI 0.02-0.07; p<0.001).
Emicizumab prophylaxis also was associated
with a significantly lower incidence of treated
bleeding events, compared with no prophylaxis
(primary endpoint). Over a ≥24-week treatment
period, all members of group C reported at least
one treated bleeding event, while 56 percent of
people receiving once-weekly emicizumab and 60
percent of people receiving biweekly emicizumab
reported no treated bleeding events.
In group D, the annualized bleeding rates
(ABRs) for those receiving once-weekly emici-
zumab versus FVIII prophylaxis were 1.5 events
(range = 1.0-2.3) and 4.8 events (range = 3.2-7.1),
respectively, “a result that indicated a 68-percent
lower rate in favor of emicizumab prophylaxis
Annualized Bleeding Rate Among Participants Receiving
Emicizumab or No Prophylaxis
TABLE 2.
Median duration of efficacy period, weeks (range)
Annualized rate of bleeding events treated with FVIII
Group A:
Emicizumab
Once Weekly (n=36) Group B:
Emicizumab Every
2 Weeks (n=35) Group C:
No Prophylaxis
(n=18)
29.6 (17.3–49.6) 31.3 (7.3–50.6) 24.0 (14.4–25.0)
1.5 (0.9–2.5) 1.3 (0.8–2.3) 38.2 (22.9–63.8)
Percent of participants with 0 bleeding events
treated with FVIII 56 (38–72) 60 (42–76) 0 (0–18)
Percent of participants with 0–3 bleeding events
treated with FVIII 92 (78–98) 94 (81–99) 6 (<1–27)
Annualized rate of joint bleeding events 1.1 (0.6–1.9) 0.9 (0.4–1.7) 26.5 (14.7–47.8)
Annualized rate of target-joint bleeding events 0.6 (0.3–1.4) 0.7 (0.3–1.6) 13.0 (5.2–32.3)
FVIII = factor VIII
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