ASH Clinical News November 2016 | Page 51

CLINICAL NEWS

Andexanet
Alfa Reduces
Anti-Factor Xa
Activity for
Patients With
Acute Major
Bleeding
Factor Xa (FXa) inhibitors, such as the
direct oral anticoagulants rivaroxaban
and apixaban, are safe and effective for
the treatment of venous thromboembolism and stroke in patients with atrial
fibrillation, though enthusiasm about
their use has been tempered by the risk
of major bleeding and the lack of reversal agents. Preliminary results from the
ongoing ANNEXA-4 (Andexanet Alfa,
a Novel Antidote to the Anticoagulation Effects of FXA Inhibitors) study
suggest that andexanet alfa, a recombinant modified human factor Xa decoy
protein, can rapidly reverse anti-FXa
activity and lead to hemostasis in patients with acute major bleeding.

“Prolonged
reversal of
FXa inhibition
may not be
necessary to
achieve a good
hemostatic
response.”
—STUART J. CONNOLLY, MD

“Andexanet has been designed and
developed specifically to reverse the
effects of both direct and indirect FXa
inhibitors,” study authors, led by Stuart
J. Connolly, MD, of the Population
Health Research Institute at McMaster
University in Canada, wrote in their

ASHClinicalNews.org

report, which was published in the New
England Journal of Medicine. “On the basis of a descriptive preliminary analysis,
an initial bolus and subsequent twohour infusion of andexanet substantially
reduced anti-factor Xa activity in patients
with acute major bleeding associated with
factor Xa inhibitors.”
The ongoing, multicenter, prospective,
open-label, single-group ANNEXA-4
study is evaluating the use of andexanet

in patients with acute major bleeding that
is potentially life-threatening. Patients
were enrolled starting on April 10, 2016,
from 20 centers in the United States, one
center in the United Kingdom, and one
center in Canada; the current analysis
describes the 67 patients for whom data
were complete as of June 17, 2016.
Adult patients were eligible for the
study if they received apixaban, rivaroxaban, edoxaban, or enoxaparin within the

previous 18 hours (at a dose of at least
1 mg/kg of body weight per day for
enoxaparin) for acute major bleeding.
Acute major bleeding was defined as:
• potentially life-threatening
acute overt bleeding with signs
or symptoms of hemodynamic
comp romise (e.g., severe
hypotension, poor skin perfusions,
mental confusion, or low cardiac

The first and only rFIX therapy that
delivers high-level protection
with up to 14-day dosing*

ABOVE

UP TO

5%

ZERO
BLEEDS

Factor IX (FIX) levels
above 5% over
14 days at 75 IU/kg

Median annualized
spontaneous
bleeding rate (AsBR)
of zero in 7- and 14-day
prophylaxis

14-DAY

DOSING*

Greater freedom
from infusions

median AsBR

for 14 days

*In well-controlled patients 12 years and older, defined as
1 month without spontaneous bleeding on a weekly
dose of ≤40 IU/kg.

Important Safety Information
IDELVION is indicated in children and adults with
hemophilia B (congenital Factor IX deficiency) for:
• On-demand control and prevention of bleeding episodes
• Perioperative management of bleeding
• Routine prophylaxis to prevent or reduce the frequency of
bleeding episodes
IDELVION is not indicated for induction of immune tolerance
in patients with hemophilia B.
IDELVION is contraindicated in patients who have had
life-threatening hypersensitivity to the product or its
components, including hamster proteins.
IDELVION is for intravenous use only. IDELVION can be selfadministered or administered by a caregiver with training
and approval from a healthcare provider or hemophilia
treatment center. Higher dose per kilogram body weight or
more frequent dosing may be needed for pediatric patients.
Hypersensitivity reactions, including anaphylaxis, are
possible. Advise patients who self-administer to immediately
report symptoms of hypersensitivity, including angioedema,

chest tightness, hypotension, generalized urticaria,
wheezing, and dyspnea. If symptoms occur, discontinue
IDELVION and administer appropriate treatment.
Development of neutralizing antibodies (inhibitors) to
IDELVION may occur. If expected Factor IX activity plasma
levels are not attained or bleeding is not controlled with
appropriate dose, perform an assay to measure Factor IX
inhibitor concentration. Factor IX activity assay results may
vary with the type of activated partial thromboplastin time
reagent used.
Thromboembolism (eg, pulmonary embolism, venous
thrombosis, and arterial thrombosis) can occur when
using Factor IX-containing products. In addition, nephrotic
syndrome has been reported following immune tolerance
induction in hemophilia B patients with Factor IX inhibitors
and allergic reactions to Factor IX.
The most common adverse reaction (incidence ≥1%)
reported in clinical trials was headache.

Please see brief summary of full prescribing information
on following page.

Visit us at IDELVION.com

IDELVION is manufactured by CSL Behring GmbH and distributed by CSL Behring LLC.
IDELVION® is a registered trademark of CSL Behring Recombinant Facility AG.
Biotherapies for Life® is a registered trademark of CSL Behring LLC.
©2016 CSL Behring LLC 1020 First Avenue, PO Box 61501, King of Prussia, PA 19406-0901 USA
www.CSLBehring-us.com www.IDELVION.com IDL16-03-0077a 4/2016

®

CoagulationFactor IX (Recombinant),Albumin FusionProtein