CSL Behring presenteert onderzoeksresultaten over hemofilie op ISTH
ArrayOp het gebied van recombinant bloed factor onderzoek en ontwikkeling komt er steeds meer informatie en ook dynamiek over de hele wereld neemt toe. CSL Behring presenteert nieuwe wetenschappelijke gegevens over haar onderzoeksresultaten voor de behandeling van hemofilie A en B. De gegevens worden gepresenteerd het ISTH congres in Amsterdam deze week.
RIX-FP, CSL Behring’s kandidaatgeneesmiddel bij hemofilie B laat in klinische studies zien dat de klinische werkzaamheid beschikbaar kan komen in een eenmaal wekelijkse dosering, zo blijkt uit fase I / II studie. CSL Behring kiest voor een nieuwe benadering voor de ontwikkeling van haar RIX-FP kandidaat, zij baseert zich daarbij op een nieuwe technologie genaamd de albumin fusion protein platform. 
Recombinant albumine is een belangrijke component, gezien zijn inherent lange halfwaardetijd en duurzame werking. Een behandeling met een middel met een langere halfwaardetijd kan leiden tot de een kleinere minder noodzakelijke infusies bij patiënten met hemofilie, welke behandeling eenvoudiger te beheren is en de waarschijnlijkheid een betere patiëntacceptatie mogelijk maakt en zelfs van van profylactische therapie. Momenteel beschikbare FIX producten hebben een korte halfwaardetijd, die 2-3 keer per week intraveneuze, als profylactische behandeling beschikbaar zijn welke een significante vermindering van het aantal bloedingen geeft.
Bovendien zijn farmacokinetische resultaten voor CSL Behring’s onderzoek naar recombinant rVIII-SingleChain beter omdat ze een betere halfwaardetijd hebben met octocog alfa (de comparator) bij patiënten met hemofilie A. Het onderzoek laat ook zien het veiligheid en werkzaamheid profiel vooruitgang heeft geboekt en dat geeft vertrouwen voor late-fase klinische ontwikkeling. CSL Behring’s rVIII-SingleChain is het eerste en enige recombinant factor therapie die een sterke covalente binding heeft en de stabiliteit en halfwaardetijd van factor VIII (FVIII).
CSL Behring presents scientific data on hemophilia at ISTH
As the field of recombinant blood factor research and development begins to expand and gain momentum around the world, CSL Behring is presenting new scientific data on its investigational products for the treatment of hemophilia A and B. The data is being presented at at the International Society on Thrombosis and Haemostasis (ISTH) congress in Amsterdam this week.
CSL Behring’s hemophilia B clinical candidate, rIX-FP, showed clinical efficacy of a once-weekly dosing regimen in a Phase I/II study. CSL Behring is taking a novel approach to the development of its rIX-FP candidate, basing it on a new technology called the albumin fusion protein platform. Recombinant albumin is a key component, given its inherently long half-life (a measure of how long the drug lasts in the body) and durability. A treatment with a longer half-life could result in the need for fewer infusions by patients with hemophilia, which may make treatment easier to manage and increase the likelihood of patient acceptance of prophylactic therapy. Currently available FIX products have a short half-life, requiring two to three times weekly intravenous prophylactic treatment to achieve a significant reduction of bleeding.
Additionally, pharmacokinetic results for CSL Behring’s investigational recombinant rVIII-SingleChain showed improved half-life over octocog alfa (the comparator) in patients with hemophilia A. It also demonstrated a safety and efficacy profile that supports advancement to late-stage clinical development. CSL Behring’s investigational rVIII-SingleChain is the first and only single-chain designed recombinant factor therapy that uses a strong, covalent bond that has been shown to improve the stability and half-life of factor VIII (FVIII).
CSL Behring Presents Phase I Results From Study of Recombinant Fusion Protein Linking Coagulation Factor VIIa with Albumin (rVIIa-FP) in Healthy Volunteers
Recombinant albumin fusion platform forms basis of innovation
Amsterdam, Netherlands— July 3, 2013 2013 – CSL Behring today presented Phase I data of their recombinant fusion protein linking coagulation factor VIIa with albumin (rVIIa-FP) in healthy volunteers at the International Society on Thrombosis and Haemostasis (ISTH) congress in Amsterdam.
CSL Behring, in collaboration with its parent company, CSL Limited (ASX: CSL), is developing rVIIa-FP, a novel therapy to treat hemophilia A and hemophilia B patients who have inhibitors (antibodies that develop in response to treatment with other clotting factors that prevents those treatments from working) as part of the PROLONG 7- FP clinical study program. The objective of the clinical program is to demonstrate that an extended half-life rVIIa-FP will result in a requirement for fewer doses while providing adequate therapeutic response in patients with hemophilia A and B with inhibitors.
“Our goal is to pioneer therapeutic solutions that address real unmet needs in the hemophilia community,” said Dr. Debra Bensen-Kennedy, Global Therapeutic Head of Clinical Research and Development at CSL Behring. “With our recombinant albumin fusion technology, we believe we have an innovative and promising approach that may yield long-acting therapies with the potential to truly advance hemophilia treatment.”
About the Phase I study
The study enrolled a total of 40 healthy male volunteers between 18 and 35 years of age, who were dosed in five consecutive dose cohorts (140, 300, 500, 750 and 1000 µg /kg). In each cohort, six participants were randomized to a single dose of rVIIa-FP and two to placebo. All participants received anticoagulation with oral vitamin K antagonist to reach an international normalized ratio (INR) between 2 and 3 prior to dosing with rVIIa-FP or placebo.
About rVIIa-FP
rFVIIa is an activated form of factor VII and can bypass the need for factor VIII or IX in people with hemophilia who have developed inhibitors to clotting factor concentrates to restore factor VIII or IX. Preclinical studies have confirmed that CSL Behring’s rVIIa-FP has favorable pharmacokinetic properties compared with the existing recombinant FVIIa product. Significant increases in half-life have been observed with CSL Behring’s rVIIa-FP across all animal species. The use of a bypassing agent with an extended half-life could offer significant benefit to those affected by hemophilia A or B with inhibitors and may offer patients the opportunity to be treated less frequently than with the currently available product.
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. The incidence of inhibitors in individuals with hemophilia A is estimated to be 33 percent and 1 to 6 percent in patients with hemophilia B.
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
Amsterdam, Netherlands— July 2, 2013 – 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.
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/.
CSL Behring, specialists in hemophilia and other rare bleeding disorders, is based in King of Prussia, PA. For more information on CSL Behring, please visit: www.cslbehring.com.
