Published: December 16, 2011
FDA Approves Baxter's ADVATE as the Only FVIII for Routine Prophylaxis in Both Adults and Children With Hemophilia A
DEERFIELD, Ill. - (BUSINESS WIRE) - Baxter International Inc. today announced that the U.S. Food and Drug
Administration (FDA) has approved ADVATE [Antihemophilic Factor
(Recombinant) Plasma/Albumin Free Method] for routine prophylaxis to
prevent or reduce the frequency of bleeding episodes in patients with
hemophilia A. ADVATE is the only antihemophilic factor approved in the
United States for prophylactic use in both adults and children.
The approval is based on a Phase IV prophylaxis study sponsored by
Baxter demonstrating that ADVATE for routine prophylaxis significantly
reduced median annual bleed rates (ABR) in hemophilia A patients from 44
to one as compared to an on-demand regimen. Forty-two percent of study
patients experienced zero bleeds during one year on prophylaxis. Of the
two prophylactic regimens approved for use, the dosing schedule of every
three days, a pharmacokinetic-driven regimen based on patient's clinical
response, offered some patients the option of fewer infusions over one
year of treatment.
"Emerging data provide important information to help physicians optimize
care for hemophilia patients of all ages by preventing unexpected
bleeding events that can have a detrimental impact on the lives of
patients," said Leonard Valentino, M.D., Director, Rush Hemophilia and
Thrombophilia Center and Section of Pediatric Hematology/Oncology, Rush
University Medical Center, Chicago, and lead investigator of this study.
"These data confirm the important clinical benefits of ADVATE when used
as a prophylactic therapy to reduce bleeding episodes."
The study findings demonstrated a statistically significant reduction in
the median annual bleeding rate, with patients experiencing 44 bleeds
(per patient per year) during on-demand treatment compared to one bleed
(per patient per year) while on either of the prophylactic regimens
evaluated, a 98 percent reduction in annual bleed rate (p<0.0001).
Nearly half (42 percent) of patients experienced no bleeding episodes
while on one year of prophylactic treatment. Evaluable patients had
greater than or equal to 90 percent adherence to the prescribed
prophylactic regimen. While the trial was not powered to demonstrate
equivalence in bleeding rate between the two prophylaxis arms, there was
no statistically significant difference in bleeding frequency observed
between the two prophylaxis regimens studied.
"This latest clinical milestone for ADVATE is an important step forward
for people living with hemophilia A as we continue to research ways to
advance care for this patient population," said Bruce Ewenstein, M.D.,
Ph.D, vice president, clinical affairs, Baxter's BioScience business.
"This rigorous clinical study demonstrated that the number of bleeding
episodes experienced each year could be reduced to as low as one event
with prophylactic treatment. Further, the pharmacokinetic-driven dosing
regimen based on patient's clinical response every third day, offers
some patients the option of fewer infusions over one year of treatment
than the current standard prophylaxis regimen."
For the prophylaxis regimen to prevent or reduce frequency of bleeding
episodes, ADVATE dosing of three to four times weekly (between 20 to 40
international units of factor VIII per kg body weight every other day)
may be used. Alternatively, an every third day dosing regimen targeted
to maintain FVIII trough levels greater than or equal to one percent may
be employed. The serious adverse drug reactions (ADRs) seen with ADVATE
are hypersensitivity reactions and the development of high-titer
inhibitors necessitating alternative treatments to Factor VIII. The most
common ADRs observed in clinical trials (frequency ≥ 10% of patients)
were pyrexia, headache, cough, nasopharyngitis, vomiting, arthralgia,
limb injury.
Study Design
The approval is based on the ADVATE Phase IV study comparing two
prophylactic regimens to on demand treatment of bleeding episodes in
previously treated patients with severe or moderately severe hemophilia
A. The multi-center, open-label, prospective, randomized, controlled
clinical trial evaluated the relative efficacy of ADVATE use in two
prophylactic regimens (standard prophylaxis [20-40 international
units/kg every 48 hours] and pharmacokinetic-driven prophylaxis [20-80
international units/kg every 72 hours, targeted to maintain FVIII trough
levels at least 1 percent or higher]) compared to that of on-demand
treatment in 53 previously treated patients with severe to moderately
severe hemophilia A. Initial treatment with six months of on-demand
therapy was followed by 12 months of either prophylactic regimen.
All patients had a history of at least eight joint hemorrhages per year
prior to entering the study. Additionally, each patient evaluated was
adherent to greater than 90 percent of the prescribed number of
prophylactic infusions, and no patient in the study surpassed the upper
boundary of 110 percent of the prescribed number of prophylactic
infusions.
About ADVATE
ADVATE was initially approved by the FDA in July 2003 for control and
prevention of bleeding episodes in adults and children with hemophilia
A. ADVATE (derived from the complete FVIII gene) is a recombinant FVIII
therapy that is processed without any blood-based additives. Because no
blood-derived components are added at any stage of the manufacturing
process, the potential risk of transmitting pathogens that may be
carried in blood-based additives is eliminated. There have been no
confirmed reports of transmission of HIV, HBV or HCV with any rFVIII
therapies.
ADVATE is approved in 52 countries worldwide including the United
States, Canada, 27 countries in the European Union, Argentina,
Australia, Brazil, Chile, Colombia, Croatia, Hong Kong, Iceland, Iraq,
Japan, Macau, Malaysia, New Zealand, Norway, Puerto Rico, Serbia,
Singapore, South Korea, Suriname, Switzerland, Taiwan, Uruguay and
Venezuela. Since the initial approval of ADVATE eight years ago, nearly
10 billion international units have been distributed, and ADVATE is the
number one chosen rFVIII worldwide.
ADVATE is an Antihemophilic Factor (Recombinant) indicated for:
-
Control and prevention of bleeding episodes in adults and children
(0-16 years) with Hemophilia A
-
Perioperative management in adults and children (0-16 years) with
hemophilia A
-
Routine prophylaxis to prevent or reduce frequency of bleeding
episodes in adults and children (0-16 years) with hemophilia A
-
ADVATE is not indicated for the treatment of von Willebrand disease
Detailed Important Risk Information for ADVATE
ADVATE is contraindicated in patients with known anaphylaxis to mouse or
hamster protein or other constituents of the product.
Allergic-type hypersensitivity reactions, including anaphylaxis, are
possible and have been reported with ADVATE. Symptoms have manifested as
dizziness, paresthesia, rash, flushing, face swelling, urticaria,
dyspnea, and pruritus. Discontinue use if hypersensitivity symptoms
occur and administer appropriate emergency treatment.
Patients treated with AHF products should be monitored for the
development of FVIII inhibitors. Inhibitors have been reported following
administration of ADVATE predominantly in previously untreated patients
(PUPs) and previously minimally treated patients (MTPs).
If expected plasma FVIII levels are not attained, or if bleeding is not
controlled with an expected dose, test for the presence of inhibitors.
The most serious adverse reactions seen with ADVATE are hypersensitivity
reactions and the development of high-titer inhibitors necessitating
alternative treatments to FVIII.
The most common adverse reactions observed in clinical trials (frequency
less than 10% of patients) were pyrexia, headache, cough,
nasopharyngitis, vomiting, arthralgia, and limb injury.
Please see full prescribing information at www.baxter.com/downloads/healthcare_professionals/products/ADVATE_PI.pdf.
About Hemophilia
Hemophilia is a rare genetic blood clotting disorder that primarily
affects males.1 People living with hemophilia do not have
enough of, or are missing, one of the blood clotting proteins naturally
found in blood.1 Two of the most common forms of hemophilia
are A and B.2 In people with hemophilia A, clotting factor
VIII is not present in sufficient amounts or is absent.2 Without
enough FVIII, people with hemophilia can experience spontaneous,
uncontrolled internal bleeding that is painful, debilitating, damaging
to joints and potentially fatal.2 People with hemophilia B
(also called Christmas disease) do not have sufficient amounts of
clotting factor IX.2 In about 30% of cases, there is no
family history of hemophilia and the condition is the result of a
spontaneous gene mutation.3 According to the World Federation
of Hemophilia, more than 400,000 people in the world have hemophilia.1 All
races and economic groups are affected equally.1
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, cancer, 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.
1. What is Hemophilia? World Federation of Hemophilia. Accessed on: 29
June 2011. Available at: www.wfh.org/2/1/1_1_Hemophilia.htm.
2. Frequently Asked Questions About Hemophilia. World Federation of
Hemophilia. Accessed on: 29 June 2011. Available at: http://www.wfh.org/2/1/1_1_1_FAQ.htm#difference.
3. Hemophilia A. National Hemophilia Foundation. Accessed on: 29 June
2011. Available at: http://www.hemophilia.org/NHFWeb/MainPgs/MainNHF.aspx?menuid=180&contentid=45&rptname=bleeding.
Baxter International Inc.
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