CSL Behring Announces Results from Study of Recombinant Single-Chain Factor VIII (rVIII-SingleChain) for Treatment of Hemophilia

 CSL Behring Announces Results from Study of Recombinant Single-Chain Factor
            VIII (rVIII-SingleChain) for Treatment of Hemophilia A

Pharmacokinetic results indicate rVIII-SingleChain may have advantages over
multi-chain rFVIII

PR Newswire

AMSTERDAM, July 2, 2013

AMSTERDAM, July 2, 2013 /PRNewswire/ --CSL Behring today announced that
pharmacokinetic results for its novel investigational recombinant coagulation
single-chain factor VIII (rVIII-SingleChain) showed improved half-life over
octocog alfa (the comparator). It also demonstrated a safety and efficacy
profile that supports advancement to late-stage clinical development. The data
were presented at the International Society on Thrombosis and Haemostasis
(ISTH) congress in Amsterdam.

(Logo: http://photos.prnewswire.com/prnh/20130627/NY39350LOGO )

CSL Behring, in collaboration with its parent company, CSL Limited (ASX:CSL),
is developing rVIII-SingleChain for the treatment of hemophilia A as part of
the AFFINITY clinical trial program.

"These data are promising and suggest that the recombinant single-chain design
for Factor VIII may help address the need for a hemophilia A treatment with a
longer half-life," said Professor Ingrid Pabinger-Fasching, M.D., of the
Medical University of Vienna, Austria. "A treatment with an improved half-life
has the potential to increase the quality of life for those with severe
hemophilia A by reducing the number of factor VIII protein infusions required
to restore normal blood clotting."

The CSL Behring rVIII-SingleChain design uses a strong, covalent bond shown to
improve the stability and half-life of factor VIII (FVIII). The
investigational treatment is currently being studied in a Phase III trial.

"As part of our commitment to developing effective therapies to treat
hemophilia, we sought to develop a novel recombinant single-chain Factor VIII
design that improves the stability and half-life of factor VIII," said Russell
Basser, M.D., CSL Senior Vice President, Global Clinical Research &
Development. "We are encouraged by these clinical results and very pleased
that our investigation of rVIII-SingleChain molecule has progressed to Phase
III."

About the Pharmacokinetic Study

The study enrolled 27 participants >18 years old with severe hemophilia A.
Study participants had pharmacokinetic (PK) measurements performed over 72
hours for both octocog alfa and rVIII-SingleChain after they had received a
single infusion of 50 IU/kg body weight of each of the compounds,
respectively. In between study drug administration there was a 4-day minimum
washout phase. Study objectives comprised the characterization of the PK
profile of rVIII-SingleChain, the PK comparison of rVIII-SingleChain to
octocog alfa and the characterization of the safety profile of
rVIII-SingleChain.

The pharmacokinetics of rVIII-SingleChain and octocog alfa were assessed on
the basis of FVIII activity. The following PK parameters were calculated for
baseline-corrected FVIII activity using a non-compartmental model analysis
with WinNonlin Phoenix (Version 6.3): The area under the plasma activity-time
curve from time zero to the last quantifiable concentration (AUClast); the
area under the plasma activity-time curve from time zero to infinity (AUCinf);
the observed maximum plasma activity after drug administration (Cmax);
incremental Recovery (IU/mL/IU/kg) defined as FVIII activity (IU/mL) obtained
30 minutes following infusion; clearance (CL), and terminal elimination
half-life (t½).

About the AFFINITY Phase I/III Study

The AFFINITY Phase I/III study is an open-label, multi-center trial that
examines the crossover safety, efficacy and pharmacokinetics of recombinant
coagulation single-chain factor VIII compared with recombinant human
antihemophilic factor VIII (octocog alfa).

In Part 1 of the study, 27 subjects received a single infusion of 50 IU/kg
body weight (b.w.) of octocog alfa followed by a single infusion of 50 IU/kg
b.w. rVIII-SingleChain. In Parts 2 and 3 of the study, subjects will receive
infusions of rVIII-SingleChain to prevent and treat bleeding (if required), at
a dose and frequency determined by their study doctor (based on the subject's
underlying bleeding phenotype). More information about the study design can be
found at www.clinicaltrials.gov.

About rVIII-SingleChain

Recombinant FVIII molecules so far available consist of a heavy and a light
chain. Under certain conditions, these chains can dissociate, resulting in the
formation of separated, or "dissociated," rFVIII chains that are not
hemostatically active. The CSL Behring rVIII-SingleChain uses a strong,
covalent bond that connects the light and heavy chains, thereby creating a
stable single chain rFVIII.

In-house CSL Behring studies have shown that the molecular integrity of
rVIII-SingleChain is significantly increased using the single-chain design,
resulting in a homogenous product that is more stable than currently available
FVIII products. In addition, in-vitro studies have shown that
rVIII-SingleChain demonstrates a strong affinity for von Willebrand factor
(VWF), resulting in a faster and more efficient binding to VWF. The FVIII/VWF
complex plays an important role in the physiological activity and clearance of
FVIII and has been shown to have an influence on the presentation of FVIII to
the immune system.

The research leading to the initiation of the studies that CSL Behring is now
conducting is the result of collaboration across the CSL Behring research
sites in Marburg, Germany, in King of Prussia, USA, and at laboratories
operated by CSL Limited in Melbourne, Australia.

About Hemophilia
Hemophilia is an inherited bleeding disorder characterized by prolonged or
spontaneous bleeding, especially into the muscles and joints. In nearly all
cases, it affects only males. The disease is caused by deficient or defective
blood coagulation proteins known as factor VIII or IX. The most common form of
the disease is hemophilia A, or classic hemophilia, in which the clotting
factor VIII is either deficient or defective. Hemophilia A affects
approximately 1 in 5,000 to 10,000 people. Hemophilia B is characterized by
deficient or defective factor IX. Hemophilia B affects approximately 1 in
25,000 to 50,000 people. The recommended treatment for patients who are factor
deficient is to treat by replacement factor therapy.

About CSL Behring
CSL Behring is a leader in the plasma protein therapeutics industry. Committed
to saving lives and improving the quality of life for people with rare and
serious diseases, the company manufactures and markets a range of
plasma-derived and recombinant therapies worldwide.

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
diseases in the newborn. CSL Behring operates one of the world's largest
plasma collection networks, CSL Plasma. CSL Behring is a subsidiary of CSL
Limited (ASX:CSL), a biopharmaceutical company headquartered in Melbourne,
Australia. For more information, visit http://www.cslbehring.com/.

Media Contact:
Sheila A. Burke, Director, Communications & Public Relations
Worldwide Commercial Operations
CSL Behring
610-878-4209 (o)
484-919-2618 (c)
Sheila.Burke@cslbehring.com

SOURCE CSL Behring

Website: http://www.cslbehring.com
 
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