R&D continues to provide support to our immunoglobulin (Ig) franchise. Following successful approval for the biweekly administration and flexible dosing of HIZENTRA® subcutaneous immunoglobulin last year in the US and Europe, approval was granted in Australia in April 2016, and a submission for approval was made to New Zealand authorities in May 2016.
HIZENTRA, the first and only 20% subcutaneous immunoglobulin, is an important treatment option for people diagnosed with primary and secondary immunodeficiencies. The ability to customise the dosing regimen of HIZENTRA provides physicians with more options to meet the individual needs of patients on Ig therapy. It also provides 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.
Advancement of the development of a family of novel recombinant coagulation factor medicines to progress the care of people with haemophilia and other coagulation disorders continued during 2015/16. Major highlights included completion of pivotal studies and registration in US and European markets of our long-acting fusion protein linking recombinant coagulation factor IX with recombinant albumin (IDELVION) for the treatment of haemophilia B, and registration in the US of our novel factor VIII single chain (AFSTYLA) indicated for adolescents and adults with haemophilia A.
Other advancements included the subcutaneous extended half-life rIX-FP product for the prophylactic treatment of haemophilia B patients recently entering Phase I studies, and rVIIa-FP (recombinant fusion protein linking coagulation factor VIIa with albumin), which continues to progress through human clinical trials for multiple patient groups.
Significant progress has been made in unlocking the medical significance and value of our specialty plasma-derived products. The US Food and Drug Administration (FDA) has approved the use of BERINERT® (C1 esterase inhibitor [human]) for treating hereditary angioedema (HAE) attacks, for use in paediatric patients. This expands the use of BERINERT into all age groups, making it the first and only approved HAE treatment available to patients under 12 years of age. In addition to the paediatric indication, the FDA approved an update to the geriatric use section of the package insert. The safety and efficacy of BERINERT have been established in both children and adults, with safety profiles in the paediatric and geriatric populations similar to that observed in other populations. Clinical studies have shown that intervention with BERINERT at the onset of an HAE attack brings significantly faster relief to a patient and reduces the severity of the attack.
An international Phase III study has been successfully completed, demonstrating the use of a volume-reduced, subcutaneous formulation of C1-esterase inhibitor concentrate (C1-Inh) for treatment of patients with frequent HAE attacks. Based on this data, a regulatory submission for HAEGARDA™ was accepted by the FDA in August 2016.
BERIPLEX® (4 factor prothrombin complex concentrate) received Orphan Drug Designation in Japan in March 2016, as a first-in-class therapy to reverse the effects of vitamin K antagonists (e.g. warfarin) for bleeding related to over-anticoagulation and patients needing urgent surgery.
An R&D priority is the development of new breakthrough medicines such as CSL112, a novel formulation of apolipoprotein A-I (apoA-I). 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. AEGIS-I, a Phase IIb global placebo controlled, dose ranging study investigating the safety and tolerability of multiple dose administration of CSL112 in 1,200 patients who experienced an acute myocardial infarction or heart attack, has been completed. Results from this study were presented in November 2016, and results for an ongoing study in patients with renal impairment are expected throughout 2017.
Significant progress has also been made in the earlier stage recombinant monoclonal antibody (mAb) projects. A first-in-human study to evaluate the use of a human antibody (CSL324) that neutralises G-CSF activity for the treatment of inflammatory diseases associated with neutrophil infiltration was recently commenced following the successful completion of non-human primate and other studies that demonstrated CSL324 to be safe and well tolerated.
Earlier stage R&D pipeline advances include the continuation of a Phase II study for CSL362 (anti-IL-3R mAb) in acute myeloid leukaemia and the commencement of an exploratory study to evaluate the use of CSL362 in systemic lupus erythematosus patients by our partner Janssen Biotech Inc.
The combined influenza vaccine portfolio derived from bioCSL and Novartis influenza vaccine business (NVS-IV) involves several late stage projects, mostly involving the development of quadrivalent versions to replace/supplement trivalent vaccines. All seasonal and pandemic influenza vaccine projects are either in Phase III or registration/launch, with five regulatory agency approvals received in 2016 alone.
In May 2016, the FDA approved FLUCELVAX QUADRIVALENT™, a quadrivalent influenza vaccine (QIV) for use in people aged four years and above in the US. FLUCELVAX QUADRIVALENT is the first and only FDA approved QIV that is manufactured using cell-based technology. In November 2015, the FDA approved FLUAD™, an adjuvanted trivalent influenza vaccine (TIV) for use in adults aged 65 years and older in the US. FLUAD is the world’s only licensed adjuvanted seasonal influenza vaccine.