Clinical Research Studies
Current CSL Behring Studies
CSL R&D drives innovation in immunoglobulins, specialty plasma products, hemophilia products, breakthrough medicines, vaccines and licensing.
CSL maintains its leadership position in intravenous and subcutaneous immunoglobulin therapies by developing new therapy options with greater convenience for patients and healthcare practitioners.
CSL continues to enhance its immunoglobulin portfolio by expanding global registration of Privigen™, its state-of-the-art chromatographic intravenous immunoglobulin (IVIg) in the US and Europe. Privigen™ is a high-yield, proline-stabilised IVIg that is ready for immediate use, requiring no refrigeration or reconstitution. The product is intended for patients diagnosed with primary immunodeficiency (PI) and chronic immune thrombocytopenic purpura (ITP).
In April 2010, the US Food and Drug Administration (FDA) approved a supplemental Biologics License Application to extend the shelf life for Privigen™, Immune Globulin Intravenous (Human), 10% Liquid, from 24 to 36 months. The approval makes Privigen™ the first liquid intravenous immunoglobulin in the US that can be stored at room temperature throughout its entire 36-month shelf life.
CSL is also strengthening its presence in the neurology market and have now concluded its Phase III study assessing the use of Privigen™ in the treatment of patients with CIDP (Chronic Inflammatory Demyelinating Polyneuropathy), a rare neurological disorder of the peripheral nerves. This study showed improved function in patients with CIDP treated with Privigen™ and in April 2013 CSL was granted marketing authorization in Europe.
During 2009/10, the clinical development of CSL's 20% subcutaneous immunoglobulin product was completed. On 4 March 2010, the US FDA granted marketing approval for Hizentra™, Immune Globulin Subcutaneous (Human), 20% Liquid, for treating patients diagnosed with primary immunodeficiency (PI). Hizentra™ is the first 20% subcutaneous immunoglobulin (SCIg) approved in the US by the FDA. Hizentra™ is now also approved for treating patients diagnosed with Primary Immune Deficiency or Secondary Immune Deficiency in Europe and Canada. More recently, CSL have completed a Phase III licensing study in Japan which supports the safety and efficacy of Hizentra™ and was granted approval in Japan for PID and SID in September 2013.
As the first SCIg treatment with a 20% concentration of immunoglobulin, Hizentra™ represents an effective, convenient choice of at-home Ig therapy that will allow people with PI to schedule treatment around their busy lives instead of scheduling their lives around treatment. Hizentra™ is an important addition to the rapidly growing CSL product portfolio, and further demonstrates our long-standing commitment to the PI and rare disease communities.
In September 2013 the FDA and EU approved biweekly dosing based on principles of pharmacometrics and pharmacokinetic modeling.
Following the successful completion of the study demonstrating the safety and efficacy of Privigen™ for CIDP, an international Phase III study testing Hizentra™ for this neurological condition has commenced, aiming to provide greater flexibility and control to patients who require long-term immunoglobulin therapy.
Specialty Plasma Products
CSL's focus has been on expanding the use of specialty products through new geographic markets, medical indications and/or alternate modes of administration.
RiaSTAP™ (human fibrinogen) was approved by the US FDA in January 2009 for the treatment of patients with a congenital deficiency of this coagulation protein. It is the first and only treatment for acute bleeding episodes in patients with congenital fibrinogen deficiency, an extremely rare and potentially life-threatening bleeding disorder. Following approval in Germany in late 2009, RiaSTAP™ also gained approval more broadly across Europe via completion of the mutual recognition process in July 2010.
In January 2012, CSL Behring commenced recruitment of 200 patients in a Phase III study in Europe to assess the use of RiaSTAP™ in peri-operative bleeding.
In February 2011, the US FDA granted marketing approval for Corifact™, Factor XIII Concentrate (Human), for the routine prophylactic treatment of congenital factor XIII (FXIII) deficiency. Corifact™, already available for use in 12 countries throughout the world under the trade name Fibrogammin™- P, is the first and only FXIII concentrate approved in the US. In February 2013, the US FDA approved an expansion of the indication to include the peri-operative management of surgical bleeding in patients with congenital factor XIII (FXIII) deficiency.
Congenital FXIII deficiency, also known as fibrin-stabilizing factor deficiency, is a rare and potentially life-threatening bleeding disorder in which blood clots normally, but the clots formed are unstable, leading to recurrent bleeding. It is estimated that the condition affects one person in two million, with an incidence in the US of approximately 150 people.
In April 2013, the US FDA approved Kcentra™ (Prothrombin Complex Concentrate [Human]), the first non-activated 4-factor prothrombin complex concentrate (PCC) for the urgent reversal of acquired coagulation factor deficiency induced by vitamin K antagonist (e.g., warfarin) therapy in adult patients with acute major bleeding. Approval was granted following completion of a pivotal clinical trial which showed that Kcentra™ met all efficacy and safety endpoints, including the endpoints of hemostatic efficacy and International Normalized Ratio (INR) reduction compared with plasma, the most widely used agent for warfarin reversal in the United States. Kcentra™ restored the decreased vitamin K-dependent clotting factors significantly faster than plasma in patients on warfarin and provides another option to medical professionals for stopping major bleeding in patients for whom plasma may not be optimal. In December 2013, the US FDA approved an expanded indication for Kcentra™. This new indication allows its use during urgent surgery/invasive procedures.
On 12 October 2009, the US FDA granted marketing approval for Berinert™ C1-Esterase Inhibitor for the treatment of acute abdominal or facial attacks associated with hereditary angioderma (HAE) a rare and serious genetic disorder. Berinert™, the first and only therapy approved for this indication in the US. It is now licensed in 31 countries worldwide. On 25 August 2011, CSL Behring announced that European health authorities had approved self-administration of Berinert™ and in January 2012, the US FDA also approved a label expansion for self-administration of Berinert™. A Phase II study has also recently been completed evaluating a convenient volume-reduced, subcutaneous formulation of Berinert™ in patients with HAE. A Phase III study commenced in late 2013.
CSL scientists are committed to expanding the coagulation therapies portfolio through development of recombinant coagulation factor medicines to treat hemophilia and other coagulation disorders. Recombinant forms of factors IX and Vlla are in development utilizing albumin fusion technology which extends the half life of the circulating molecules. If successful, this should result in a marked reduction in the frequency of administration and would significantly increase convenience for patients. CSL is also developing a unique single chain recombinant factor VIII (rVIII-SingleChain) for treatment of hemophilia A.
On 2 February 2012, CSL announced results of a Phase I study evaluating recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in patients with severe hemophilia B. Results of the study showed the rIX-FP was well tolerated with no serious adverse events, no presence of inhibitors to factor IX, or antibodies to rIX-FP were reported. Terminal half-life (a measure of how long the drug lasts in the body) was more than five times longer in comparison to values associated with current recombinant FIX therapy. A pivotal Phase II/III adult study was completed in 2013. Also in January 2013, the first patient was enrolled in a pivotal Phase III paediatric study to evaluate the safety, efficacy and pharmacokinetics of rIX-FP in previously treated children with haemophilia B.
On 16 February 2012, CSL announced that it had been granted Orphan Drug Designation by the US Food and Drug Administration for its novel recombinant fusion protein linking activated coagulation factor VIIa with recombinant albumin (rVIIa-FP). The Orphan Drug Designation was granted for the treatment and prophylaxis of bleeding episodes in patients with congenital hemophilia and inhibitors to coagulation factor VIII or IX. CSL have completed a Phase I study and initial pharmacokinetic data shows 3-4x half life extension. The use of a bypassing agent with extended half-life could offer significant benefits to those affected by Hemophilia A or B with inhibitors and may offer the opportunity of less frequent dosing.
CSL627, the candidate molecule being studied for the treatment of hemophilia A, is a unique single chain recombinant factor VIII (rVIII-SingleChain). In house studies have shown that the molecular integrity of CSL627 is significantly increased using the single chain design, resulting in a homogenous product that may be more stable than currently available options. In addition, in-vitro studies have shown that CSL627 demonstrates a very strong affinity for von Willebrand factor (VWF) and a faster and more efficient binding to VWF. The factor VIII/VWF complex plays an important role in the physiological activity and clearance of factor VIII and has been shown to have an influence on the presentation of factor VIII to the immune system. On 15 February 2012, CSL screened the first patient for its rVIII-SingleChain Phase I/II trial and early clinical data supports twice weekly dosing. The Phase III study was initiated in February 2013.
A research program has also been initiated for long acting rvWF-FP.
In the Breakthrough Medicines program, CSL aims to develop new protein based therapies to address significant unmet medical needs.
Significant progress has been made in the earlier stage recombinant monoclonal antibody (mAb) projects including the Anti-G-CSFR mAb (CSL324) for treating inflammatory conditions caused by an over activity of white blood cells called neutrophils.
The development of reconstituted High Density Lipoprotein (rHDL), a potential additional product from human plasma, is a priority for CSL's R&D program. Pre-clinical and Phase I results indicate that rHDL rapidly and robustly enhances the capacity of plasma to promote cholesterol efflux supporting possible use in Acute Coronary Syndrome. A Phase IIa study which commenced in early 2012 has now been successfully completed and results support mechanism of action and further development. A Phase IIb development program will be initiated in 2014.
In July 2010, CSL announced its decision to build a large scale biotechnology facility for the manufacture of therapies based on recombinant DNA technology at its site in Broadmeadows. The new facility will enable CSL to develop innovative products from its R&D pipeline for late-stage clinical trials and ultimately patient use, such as recombinant coagulation factor products or recombinant monoclonal antibodies.
The project, supported by both the Federal and Victorian State Governments, will generate significant employment opportunities and further develop Australia's biotechnology sector and medical research community. Design and construction of the new facility is now complete with test batches of recombinant proteins currently being produced. The facility is on track to start manufacture of clinical trial material in early 2014.
Vaccines & Licensing
CSL's partner AstraZeneca recently successfully completed a Phase IIa study of a monoclonal antibody targeting the GMCSF Receptor for the potential treatment of Rheumatoid Arthritis. Mavrilimumab showed a rapid and significant clinical effect compared to placebo with a safety profile supporting further clinical development.
In December 2009, CSL signed an agreement with Sanofi Pasteur, the world’s leading manufacturer of vaccines, to develop a vaccine to prevent and treat periodontitis, a severe gum disease affecting approximately 30% of adults. Candidate vaccine antigens against the bacterium Porphyromonas gingivalis, which causes periodontitis, are currently being trialed in mouse models of disease. This program is being conducted in collaboration with the Cooperative Research Centre for Oral Health Science.
Significant progress has been made in the earlier stage recombinant monoclonal antibody (mAb) projects including the Anti-IL-3R mAb (CSL362) for treating acute myeloid leukaemia (AML). CSL now has data supporting an AML minimal residual disease (MRD) indication and non-human primate and other studies also support the potentially valuable additional use of CSL362 in treating a serious autoimmune disease. In August 2012 CSL commenced a Phase I study of CSL362 in AML. In December 2013, CSL announced an agreement with Janssen Biotech Inc. (a Johnson & Johnson company) to exclusively license and develop CSL’s monoclonal antibody CSL362. This collaborative research program will support the use of CSL362 in other indications.
ISCOMATRIX® adjuvant activities continue with CSL's partners, progressing from pre-clinical to clinical development with several product candidates in the past year.
CSL's partners also continue to show confidence in CSL's ISCOMATRIX® adjuvant as a technology platform that could be used to enable the next generation of prophylatic and therapeutic vaccines. Additional licenses have been obtained from CSL's major partners with more than 40 fields of interest for research and product development.
The transfer of the ISCOMATRIX® adjuvant manufacturing process from Parkville to CSL's Kankakee, Illinois site is complete. Kankakee is now performing routine GMP manufacture of ISCOMATRIX® adjuvant at a commercial scale.