Highlights

CSL R&D drives innovation in immunoglobulins, specialty plasma products, haemophilia products, breakthrough medicines, vaccines and licensing.

Immunoglobulins

R&D continues to provide support to our immunoglobulin (Ig) franchise. During the year, a highlight was the approval of new flexible dosing for Hizentra® subcutaneous immunoglobulin. In December 2014, the EMA approved amended labelling for Hizentra® to provide the ability to individualise treatment with flexible dosing at intervals from daily to once every two weeks (biweekly). In February 2015, the US FDA similarly expanded the administration options for Hizentra® to include the ability to individualise therapy with flexible dosing.

Hizentra®, the first and only 20 percent subcutaneous immunoglobulin, is an important treatment option for people diagnosed with primary and secondary immunodeficiencies (PID and SID). The ability to customise the dosing regimen of Hizentra® provides physicians with more options to meet the individual needs of patients on Ig therapy and provides even more freedom to patients, by allowing them to manage their condition based on their individual lifestyles, while still providing a consistent level of protection against infections.

Following the successful demonstration of the safety and efficacy of Privigen® 10% intravenous immunoglobulin in treating chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), an international Phase III study is progressing testing Hizentra® for CIDP. These studies aim to provide greater flexibility and control for patients who require long-term immunoglobulin therapy.

Haemophilia and coagulation products

Advancement of the development of a family of novel longer-acting recombinant coagulation factor medicines to progress the care of people with haemophilia and other coagulation disorders continued during 2014/15. Important milestones included the completion of our Phase III studies evaluating the efficacy and long-term safety of our long-acting fusion protein linking recombinant coagulation factor IX with recombinant albumin (rIX-FP). Data from Phase III studies 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 haemophilia B.

In February 2015, the US FDA accepted for review CSL’s Biologics License Application (BLA) for rIX-FP and in March 2015, the EMA started the centralised procedure for reviewing our Marketing Authorisation Application (MAA) for rIX-FP.

During the year, we also completed our pivotal study on the efficacy and safety of our novel factor VIII single chain (rVIIISingleChain) in adolescents and adults with haemophilia A. Data from the AFFINITY Phase I/III study showed that patients using rVIII-SingleChain prophylactically to prevent bleeding were well-controlled when dosed only two or three times weekly. In late July 2015, the US FDA accepted for review CSL’s BLA for rVIII-SingleChain.

Specialty products

Significant progress has been made in unlocking the medical significance and value of our specialty plasma-derived products. An international Phase III study of a volumereduced, subcutaneous formulation of C1-esterase inhibitor concentrate (C1-Inh) continued in patients with frequent hereditary angioedema (HAE) attacks. This follows the successful completion of a Phase II study of C1-Inh administered twice weekly subcutaneously, continuing CSL’s leading position in this therapeutic area.

Kcentra® (4-factor prothrombin complex concentrate, known outside the US as Beriplex®) was launched in April 2014 in the US as a first-in-class therapy to reverse the effects of vitamin K antagonists (e.g., warfarin) for bleeding related to overanticoagulation and patients needing urgent surgery. In October 2014, we commenced a clinical program in Japan aiming to register Beriplex® for vitamin K antagonist reversal.

Unfortunately, a Phase III multi-site clinical trial in Europe evaluating the efficacy and safety of fibrinogen concentrate (FCH) in controlling bleeding in complex cardiac surgery did not meet its primary efficacy endpoint. Importantly there were no safety concerns identified in the study and this, combined with the results of other published studies, supports the role of FCH in improving haemostasis and potentially reducing the need for allogenic blood products across a number of clinical settings.

Findings from CSL’s RAPID study, the largest placebo-controlled trial ever conducted in patients with alpha-1 antitrypsin deficiency (AATD), demonstrated that the use of alpha-1 proteinase inhibitor (Zemaira®/Respreeza™) therapy may slow the progressive loss of lung tissue experienced by these critically ill patients. The results of the RAPID study, published by The Lancet during the year, showed patients with AATD treated with Respreeza™ exhibited a lower annual rate of lung density decline compared to placebo, when measured using chest computed tomography, at full inspiration. In late August 2015, the European Commission (EC) granted marketing authorisation in all European Union (EU) member states for Respreeza® to treat patients with AATD.

Breakthrough Medicines

An R&D priority is also the development of new breakthrough medicines such as CSL112, a novel formulation of apolipoprotein A-I (apoA-I). Following Phase I and IIa studies supporting possible use of CSL112 in acute coronary syndromes, in November 2014, CSL announced the launch of AEGIS-I. This Phase IIb global, randomised, placebo-controlled, dose-ranging study will investigate the safety and tolerability of multiple dose administration of CSL112 in 1,200 patients who experienced an acute myocardial infarction or heart attack. CSL112 is designed to rapidly remove cholesterol from the arteries and stabilise lesions at risk of rupture. This represents a potential new approach to reduce the high incidence of early recurrent cardiovascular events in the days and weeks following a heart attack. Results of the study are expected in 2017.

Earlier stage R&D pipeline advances include the commencement of a Phase II study for CSL362 (anti-IL-3R mAb) in acute myeloid leukaemia by our partner Janssen Biotech, Inc. CSL is delighted to have such a high-quality partner as Janssen who share our commitment to developing CSL362 as a novel monoclonal antibody (mAb) therapy for haematological cancers and autoimmune diseases.

Vaccines & Licensing

The bioCSL quadrivalent influenza vaccine development program continues to progress to plan. We successfully completed a major clinical study in adults aged over 18 and are now proceeding to further larger studies in the paediatric population using a quadrivalent (four strain) vaccine that has been formulated with our modified manufacturing process.

ISCOMATRIX® Adjuvant

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 many 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.

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