- Data supports prolonged dosing intervals up to 14 days for
routine prophylaxis in hemophilia B patients
- Majority of adult and pediatric patients using
rIX-FP for routine prophylaxis had an annualized spontaneous
bleeding rate (AsBR) of 0.00
- Surgical sub study results show single dose of rIX-FP
sufficient to maintain hemostasis during surgery
TORONTO, June 24, 2015 /PRNewswire/ -- CSL Behring
today presented data from Phase III studies evaluating the efficacy
and long-term safety of its investigational long-acting fusion
protein linking recombinant coagulation factor IX with recombinant
albumin (rIX-FP). The data, shared in three separate oral
presentations at the 2015 International Society on Thrombosis and
Haemostasis (ISTH) Congress in Toronto, support the use of rIX-FP for routine
prophylaxis, dosed once up to every 14 days, and for on-demand
treatment of bleeding episodes in previously-treated adults and
children with hemophilia B. The findings also include
efficacy and safety results supporting the use of rIX-FP in
patients undergoing surgical procedures.
"The pivotal data for rIX-FP are exciting because they suggest
the potential for prolonged dosing intervals of up to two weeks for
routine prophylaxis," said Elena Santagostino, M.D., Ph.D.,
Professor in the Medical School of Clinical and Experimental
Hematology at the University of Milan/IRCCS Maggiore Hospital, and lead
investigator. "The trials also showed that this less frequent
dosing was possible without compromising therapeutic benefit. This
suggests rIX-FP, if approved, could be an important new treatment
option, especially, for patients who lead active lifestyles and
require a prophylactic regimen."
Key Study Findings
- rIX-FP in previously-treated adults and adolescents
(abstract #OR347): The first Phase III study was a global
safety and efficacy trial assessing rIX-FP for prophylaxis
treatment once every 7, 10 and 14 days and on-demand treatment of
bleeding episodes in 63 previously-treated patients (12-61 years of
age) with hemophilia B (FIX activity < or = 2% of normal). In
one arm, 23 previously on-demand patients received only on-demand
treatment for 6 months and then switched to 7-day prophylaxis
treatment. In the other arm, 40 patients received 7-day prophylaxis
treatment for 6 months and then, if eligible, switched to a 10- or
14-day prophylaxis treatment interval for 12 to 18 months.
In patients who started on-demand treatment then switched to
prophylaxis treatment, annualized spontaneous bleeding rates (AsBR)
decreased by 100 percent from a median 15.43 during the on-demand
treatment phase to 0.00 in the prophylaxis treatment phase
(p<0.0001). Among patients who started on 7-day
prophylaxis treatment then switched to 10- or 14-day prophylaxis
treatment, the median AsBR rate was 0.00. In total, 99 percent of
bleeding events were successfully managed with one or two
infusions, with 94 percent of bleeds controlled with only one
infusion regardless of the cause or location. Patients on
14-day prophylaxis treatment used a median dose of 75 IU/kg, which
was 50 percent less therapy compared with their previously used FIX
products. None of the patients developed inhibitors to factor
IX or antibodies to rIX-FP. Related adverse events were
reported in five patients (7.9 percent). The most common adverse
reaction in clinical trials was headache. Overall, rIX-FP was
well tolerated and no safety concerns were identified.
"These data provide additional evidence of the benefits of CSL
Behring's recombinant albumin fusion technology, which was designed
to significantly reduce clearance and provide longer-lasting
hemostatic efficacy of factor IX to allow for less frequent
dosing," said Dr. Andrew
Cuthbertson, Chief Scientific Officer and Director of
R&D, CSL Limited. "CSL Behring has long been committed to
protecting the health of people living with a range of serious
medical conditions and rIX-FP exemplifies our promise to develop
and deliver innovative products that have the potential to improve
the care of patients around the world."
- rIX-FP in previously-treated children (abstract #OR346):
A second Phase III global study evaluated the safety and efficacy
of rIX-FP for prophylaxis treatment once every 7 days and treatment
of bleeding episodes in 27 children, age 1-11 years, with
hemophilia B (FIX activity < or = 2% of normal). Patients were
treated for 12 months and/or 50 exposure days.
The median AsBR was 0.00, and similar for patients under age 6 and
those between 6 and 11 years. In total, 97 percent of
bleeding episodes were successfully managed by one or two
infusions, with 89 percent treated with only one infusion.
Overall, the pharmacokinetic profile demonstrated a greater than
5-fold longer half-life, reduced clearance for rIX-FP versus other
FIX products, supporting prophylaxis treatment intervals every 7 to
14 days. Investigators rated 96 percent of the treatments as
effective (excellent or good). A total of 25 patients
achieved 50 or more exposure days. None of the patients
developed inhibitors to factor IX or antibodies to rIX-FP, and
there were no related adverse events or withdrawals from the
study.
- rIX-FP in previously-treated patients undergoing surgery
(abstract #PO253): The third study was a surgical sub-group
analysis included in the phase III studies as part of the global
PROLONG-9FP clinical program. This abstract evaluated the use of
rIX-FP to prevent bleeding during and post-surgery in 10 patients
with hemophilia B (ages 8 to 51 years). The results showed that a
single dose of rIX-FP was sufficient to maintain hemostasis during
surgery. Over the 14-day post-surgical study period, patients
needed anywhere from two to seven infusions. Both the consumption
and dosing frequency of rIX-FP were considered remarkably low based
on the type of surgery performed. The response was rated by
investigators as excellent or good during all procedures. None of
the patients developed inhibitors to factor FIX or antibodies to
rIX-FP, and there were no related adverse events or withdrawals
from the study.
About rIX-FP
CSL Behring engineered rIX-FP to provide longer lasting
hemostatic efficacy of recombinant factor IX through genetic fusion
with recombinant albumin. CSL Behring selected albumin as its
recombinant genetic fusion partner for its coagulation factor
proteins due to its long physiological half-life. In addition,
recombinant albumin has been shown to have a good tolerability
profile, low potential for immunogenic reactions and a well-known
mechanism of clearance. The cleavable linker connecting recombinant
factor IX and recombinant albumin has been specifically designed to
preserve the native function of the coagulation factor in the
fusion protein, while benefiting from recombinant albumin's long
physiological half-life.
In February 2015, the U.S. Food and Drug Administration accepted
for review CSL Behring's Biologics License Application (BLA) for
rIX-FP. In March 2015, the European Medicines Agency (EMA) started
the Centralized Procedure for reviewing CSL Behring's Marketing
Authorization Application (MAA) for rIX-FP.
The PROLONG-9FP clinical development program for rIX-FP covers
patients from the age of 1 to 61 years. Studies in the program were
conducted as open-label, multicenter, PK, safety and efficacy
studies of rIX-FP in previously treated patients with hemophilia B
(FIX < or = 2%).
Study design details for rIX-FP (CSL654) are available at
clinicaltrials.gov.
About Hemophilia B
Hemophilia B (congenital factor IX deficiency) is characterized
by deficient or defective factor IX and affects approximately 1 in
25,000 to 50,000 people. Hemophilia B is a congenital bleeding
disorder characterized by prolonged or spontaneous bleeding,
especially into the muscles, joints, or internal organs. Nearly all
hemophilia B patients are male.
About CSL Behring
The people and science of CSL Behring save lives around the
world. We develop and deliver innovative specialty biotherapies,
driven by our 100-year promise to help people with life-threatening
conditions live full lives. With 14,000 employees and operations in
30 countries, CSL Behring applies world-class R&D, high-quality
manufacturing and patient-centered management.
CSL Behring therapies are used around the world to treat
coagulation disorders including hemophilia and von Willebrand
disease, primary immune deficiencies, hereditary angioedema and
inherited respiratory disease, and neurological disorders in
certain markets. The company's products are also used in cardiac
surgery, organ transplantation, burn treatment and to prevent
hemolytic disease of the newborn.
CSL Behring operates one of the world's largest plasma
collection networks, CSL Plasma. CSL Behring is a global
biopharmaceutical company and a member of the CSL Group of
companies. The parent company, CSL Limited (ASX:CSL), is
headquartered in Melbourne,
Australia. For more information, visit
www.cslbehring.com.
Contact:
Greg Healy
CSL Behring
Office: 610-878-4841
Mobile: 610-906-4564
Greg.Healy@CSLBehring.com
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