Published: November 02, 2011
Statement on Prophylaxis with FEIBA - Study Results Published Today in The New England Journal of Medicine
DEERFIELD, Ill. - (BUSINESS WIRE) - Results from an investigator-initiated study, which evaluated whether
prophylactic use of FEIBA [Anti-inhibitor Coagulant Complex] can achieve
a decrease in the frequency of joint and other bleeding events in
patients with severe hemophilia A and inhibitors compared to on-demand
therapy, were published today in The New England Journal of Medicine.
Patients with severe hemophilia A and inhibitors are at increased risk
for serious bleeding complications. Effective strategies to prevent
bleeding in inhibitor patients have not yet been established.
Prophylaxis, where approved, is used to prevent a bleed and on-demand
treatment is used only at the time of a bleeding episode.
"The single greatest remaining challenge in the management of hemophilia
is the development of inhibitors, often occurring in young patients,
that can lead to more difficult to control and sometimes
life-threatening bleeding," said Bruce Ewenstein, M.D., Ph.D., vice
president, clinical affairs in Baxter's BioScience business. "The
Pro-FEIBA investigator-initiated study is the first randomized,
prospective, controlled clinical trial to evaluate the ability of FEIBA
prophylaxis to reduce bleeding events, which is particularly encouraging
given that there are limited treatment options available for these
patients."
The Prophylaxis with Factor Eight Inhibitor Bypassing Activity
(Pro-FEIBA) study reported that patients with severe hemophilia A
treated with FEIBA prophylactically during a six-month period
experienced a 62 percent reduction in all bleeds in the prophylaxis
period, an average of 5 bleeding events compared to an average of 13.1
during the on-demand treatment period. Sixty two percent of patients (16
of 26) were in the group that responded well to prophylaxis treatment,
defined as those who had a greater than or equal to 50 percent reduction
in overall bleeding, the target for success defined in the study
protocol. In this "good responder group," the overall reduction in
bleeding rate was 84 percent. Thirty eight percent of patients (10 of
26) had a less than 50 percent reduction in bleeding events during the
prophylactic period. In this group, bleeding was reduced by 28 percent.
Two patients had an increase in bleeding events in the prophylaxis
period.
Secondary outcome measurements were joint bleeding and target joint
bleeding. During the prophylaxis period, patients experienced a 61
percent reduction in joint bleeding, an average of 4.2 joint bleeds
versus an average of 10.8 during the on-demand treatment period. In
target joints (those most prone to frequent bleeding, such as the elbow,
knee and ankle), patients experienced a 72 percent reduction in
bleeding. The number of patients with bleeding in target joints
decreased from 18 to 11. Of those patients in the study achieving a
reduction in bleeds, all were achieved with three doses of FEIBA (85
U/kg ± 15 percent) per week.
One adverse event related to the study drug was an allergic reaction.
Three patients (9 percent) had multiple events related to central venous
access devices, including infection, bleeding, and line placement and
removal.
A limitation of the study was its relatively short duration. While joint
and other bleeding episodes were reduced during the six-month
prophylaxis period, a longer, larger, parallel design trial is needed to
determine if regular FEIBA infusions are a safe and effective treatment
option for hemophilia A patients with inhibitors. In addition, the
authors state it is not possible to draw conclusions regarding
relationships between patient age and the benefits of prophylaxis. A
Baxter-sponsored clinical study, FEIBA PROOF, is evaluating the efficacy
and safety of FEIBA prophylaxis compared to on-demand treatment in those
living with hemophilia with high-titer inhibitors.
The Pro-FEIBA study was conducted by lead investigators Cindy
Leissinger, M.D., from the Louisiana Center for Bleeding and Clotting
Disorders, Tulane University Medical Center, New Orleans, USA, and
Alessandro Gringeri, M.D., from the Department of Medicine and Medical
Specialties, Fondazione IRCCS CÃ Granda, Ospedale Maggiore Policlinico
and Università degli Studi di Milano, Milan, Italy. The lead
investigators oversaw all aspects of the study including design, data
collection and analysis and manuscript development and submission.
Baxter supplied the study drug (FEIBA) and provided a financial grant to
support the study and authoring of the manuscript. The manuscript was
subsequently revised by the authors who assumed responsibility for its
accuracy and completeness.
About the Study Design
The objective of the investigator-initiated Pro-FEIBA study was to test
if prophylaxis with FEIBA over a six-month period may be safe and
effective in preventing joint and other bleeds in severe hemophilia A
patients with inhibitors compared to on-demand treatment. Following the
initial six-month study period (with 12 patients receiving on-demand
therapy and 14 receiving prophylaxis), each group crossed-over to the
alternate treatment period for six months after a three-month wash-out
period. The crossover design produced valid results with fewer patients
than required for a parallel study design1. Thirty-four
patients were enrolled in the study, with 26 patients evaluated in the
final analysis.
About Hemophilia (A & B) and Inhibitors
Hemophilia is a rare genetic blood clotting disorder that primarily
affects males. People living with hemophilia do not have enough of, or
are missing, one of the blood clotting proteins naturally found in
blood. In people with hemophilia A, clotting factor VIII is not present
in sufficient amounts or is absent. People with hemophilia do not bleed
more profusely or faster than normal but bleed for a longer period of
time.
Hemophilia is usually inherited, and about one in every 5,000 males is
born with the disorder. About one third of new cases are caused by a new
mutation of the gene in the mother or the child. In these cases, there
is no previous history of hemophilia in the family. According to the
World Federation of Hemophilia, more than 400,000 people in the world
have hemophilia. All races and economic groups are affected equally.
Inhibitor development is considered one of the most serious adverse
reactions associated with hemophilia treatment. Studies suggest this may
occur in three out of every 10 people with severe hemophilia A and one
out of every 20 people with hemophilia B. Inhibitors are antibodies that
people with hemophilia can generate following exposure to blood clotting
factor replacement therapy. These antibodies neutralize (inhibit) the
action of clotting factor, which increases the risk of bleeding in
people with inhibitors. Hemophilia patients with inhibitors have an
increased risk of uncontrolled bleeding and bleeds are much more
difficult to control compared to patients without inhibitors.
Consequently, these patients can develop complications such as increased
need for surgery and increased complexity of surgery.
The information in this statement is intended for scientific exchange
only and is not intended for any other purpose.
About FEIBA
FEIBA is not indicated for prophylaxis use in the United States. Canada,
Italy, The Netherlands, Israel, Australia/New Zealand, Japan, South
Korea, and Taiwan also do not have a prophylaxis indication.
Indications
In the US, FEIBA NF [Anti-Inhibitor Coagulant Complex] is indicated for
the control of spontaneous bleeding episodes or to cover surgical
interventions in hemophilia A and hemophilia B patients with inhibitors.
Clinical experience suggests that patients with a Factor VIII inhibitor
titer of less than 5 B.U. may be successfully treated with
Antihemophilic Factor.
Patients with titers ranging between 5 and 10 B.U. may either be treated
with Antihemophilic Factor or FEIBA NF. Cases with Factor VIII inhibitor
titers greater than 10 B.U. have generally been refractory to treatment
with Antihemophilic Factor.
Detailed Risk Information About FEIBA NF
Thrombotic and thromboembolic events have been reported during
postmarketing surveillance following infusion of FEIBA VH or FEIBA NF,
particularly following the administration of high doses and/or in
patients with thrombotic risk factors.
The use of FEIBA NF is contraindicated:
-
In patients who have known anaphylactic or severe hypersensitivity
reactions to the product
-
In patients who are known to have a normal coagulation mechanism
-
For the treatment of bleeding episodes resulting from coagulation
factor deficiencies in the absence of inhibitors to coagulation factor
VIII or coagulation factor IX
-
In patients with significant signs of disseminated intravascular
coagulation (DIC)
-
In patients with acute thrombosis or embolism (including myocardial
infarction)
At first sign or symptoms of an infusion/hypersensitivity reaction or a
thrombotic/thromboembolic event, FEIBA NF administration should be
stopped immediately and diagnostic and therapeutic measures initiated as
appropriate.
Allergic-type hypersensitivity reactions, including severe anaphylactoid
reactions, have been reported following the infusion of FEIBA. The
symptoms include urticaria, angioedema, gastrointestinal manifestations,
bronchospasm, and hypotension; these reactions can be severe and can be
systemic.
Many of the reported cases of thromboembolic events occurred with doses
above 200 units/kg/day or in patients with other risk factors.
Infusion of FEIBA NF should not exceed single dosage of 100 U/kg and
daily doses of 200 U/kg of body weight. Patients receiving more than 100
U/kg of FEIBA NF must be monitored for the development of DIC and/or
symptoms of acute coronary ischemia. High doses of FEIBA NF should be
given only as long as absolutely necessary to stop bleeding.
FEIBA VH or FEIBA NF should be used with particular caution and only if
there are no therapeutic alternatives in patients at risk of DIC,
arterial or venous thrombosis.
If clinical signs of intravascular coagulation occur, which include
changes in blood pressure, changes in pulse rate, respiratory distress,
chest pain and/or cough, infusion of FEIBA NF should be stopped promptly.
Non-hemophilic patients with acquired inhibitors against factors VIII,
IX or XII may have both a bleeding tendency and an increased risk of
thrombosis at the same time.
FEIBA NF is made from human plasma. It may carry a risk of transmitting
infectious agents, e.g., viruses and theoretically, the
Creutzfeldt-Jakob disease (CJD) prion.
Adverse reactions reported in clinical studies with FEIBA were
anamnestic response, somnolence, dizziness, dysgeusia, dyspnea,
hypoesthesia, nausea, chills, pyrexia, chest pain and chest discomfort.
For information on FEIBA use in the United States, please visit: http://www.baxter.com/healthcare_professionals/products/feiba_nf.html
Licenses and licensing conditions may vary from country to country;
therefore please always consult your local full prescribing information.
Please check FEIBA website for information on indications approved in
other countries.
About Baxter International Inc.
Baxter International Inc., through its subsidiaries, develops,
manufactures and markets products that save and sustain the lives of
people with hemophilia, immune disorders, infectious diseases, kidney
disease, trauma and other chronic and acute medical conditions. As a
global, diversified healthcare company, Baxter applies a unique
combination of expertise in medical devices, pharmaceuticals and
biotechnology to create products that advance patient care worldwide.
Baxter and Feiba are registered trademarks of Baxter International Inc.,
its subsidiaries or affiliates.
1. Louis TA, Lavori PW, Bailar JC, 3rd, Polansky M. Crossover and
self-controlled designs in clinical research. N Engl J Med
1984;310:24-31.
Baxter International Inc.
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Spak, (847) 948-2349
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