Infection

Synagis (palivizumab) is a humanised MAb used for the prevention of serious lower respiratory tract disease caused by respiratory syncytial virus (RSV) in paediatric patients at high risk of acquiring RSV disease.

Merrem/Meronem¹ (meropenem) is a carbapenem anti-bacterial used for the treatment of serious infections in hospitalised patients.

FluMist (influenza virus vaccine live, intranasal) is a live, attenuated, trivalent influenza virus vaccine approved for active immunisation of people two to 49 years of age against influenza disease caused by influenza virus subtypes A and B contained in the vaccine.

H1N1 influenza (swine flu) vaccine was successfully developed and delivered to the HHS and is indicated for the active immunisation of individuals two to 49 years of age against influenza caused by pandemic H1N1 virus.

Cubicin™² (daptomycin) is a cyclic lipopeptide anti-bacterial used for the treatment of serious infections in hospitalised patients.

¹

Licensed from Dainippon Sumitomo Pharma Co., Ltd.

²

Licensed from Cubist Pharmaceuticals, Inc.

¹

Acquired in June 2007.

We aim to build a leading franchise in the treatment of infectious diseases through continued commercialisation of brands such as Synagis, Merrem and FluMist, effective use of our structural and genomic-based discovery technologies and antibody platforms, and continued research into novel approaches in areas of unmet medical need.

World demand for antibiotics remains high due to escalating resistance and the increased risk of serious infections in both immunosuppressed patients and ageing populations. Many bacterial infections currently have few satisfactory treatment options prompting demand for new and better therapies. The in-licensing from Forest of ceftaroline, ceftazidime/NXL-104 (CAZ104) and ceftaroline/NXL-104 (CEF104) adds to the strong AstraZeneca portfolio and reinforces our commitment to treating resistant bacterial infections.

Our focus

Our key marketed products

Merrem/Meronem is the leading carbapenem anti-bacterial and has a growing share of the intravenous antibiotic market because of its activity against bacteria resistant to many other agents. Cubicin™ is used for the treatment of serious Gram-positive infections in hospitalised patients and is sold by AstraZeneca in selected territories in Asia and the Middle East.

In the pipeline

During 2009, we licensed ceftaroline from Forest and will be responsible for its registration and marketing outside the US, Canada and Japan. Four Phase III studies have been completed for ceftaroline, with NDA filings made in December and MAA filings anticipated in 2010. Ceftaroline has demonstrated activity against a number of infections and multi-drug resistant pathogens, including MRSA.

In December we acquired Novexel (completion of the acquisition is subject to the expiry or termination of the applicable waiting period under the US Hart-Scott-Rodino Antitrust Improvements Act), a private infection research company in France, and we will collaborate with Forest on the future co-development and commercialisation of two antibiotic development programmes, CAZ104 and CEF104. CAZ104 is a combination of NXL-104 and ceftazidime, a third generation cephalosporin to which resistance has emerged. It is expected to move into Phase III development in late 2010 for serious infections requiring intensive care unit stays such as intra-abdominal, urinary tract and hospital acquired pneumonia. CEF104 is a combination of NXL-104 and ceftaroline, which is expected to move into Phase II development in late 2010 in indications where a mixed Gram-negative and Gram-positive profile can be of use, such as skin and diabetic foot infections.

To meet the high and growing need for new and better therapies for resistant bacterial infections we have also built an anti-bacterials discovery capability that places AstraZeneca among the industry leaders with the capability to create novel mechanism anti-bacterials. Out of this work, a candidate anti-bacterial drug, AZD9742, with a novel mechanism of action entered Phase I testing late in 2009.

Approximately half of all infants are infected with respiratory syncytial virus (RSV) during the first year of life and nearly all children in the US have been infected by the time they reach their second birthday. Unlike other viral infections, there is no complete and durable immunity created by RSV, so repeated infection is likely and common. Premature babies (earlier than 36 weeks gestational age, especially those less than 32 weeks) and babies with chronic lung disease or congenital heart disease are at an even greater risk of contracting severe RSV disease than full-term babies.

Our focus

Our key marketed products

Synagis is used for the prevention of serious lower respiratory tract disease caused by RSV in children at high risk of the disease. It was the first MAb approved in the US for an infectious disease and since its launch in 1998 it has become the standard of care for RSV prevention. Synagis remains the only immunoprophylaxis in the marketplace indicated for the prevention of RSV in paediatric patients at high risk of RSV. Synagis is administered by intra-muscular injection.

In the pipeline

We filed a biological licence application with the FDA for an improved anti-RSV MAb, motavizumab, and received a Complete Response Letter in 2008. We filed a formal regulatory reply to the Complete Response Letter in December 2009. We do not believe that further clinical studies will be required by the FDA for marketing approval.

In addition, an intranasal vaccine is being developed for the prevention of lower respiratory tract illness caused by RSV and parainfluenza virus-3 (PIV3) in infants. There are two RSV vaccine programmes: MEDI-559 and MEDI-534. We are conducting several Phase I and Phase I/II studies for these vaccines, both alone and in collaboration with the US National Institute of Allergy and Infectious Diseases.

Influenza is the most common vaccine-preventable disease in the developed world. According to WHO estimates, seasonal influenza results in three to five million cases of severe illness and up to half a million deaths globally each year, primarily among the elderly. Rates of infection are highest among children, with school-aged children significantly contributing to the spread of the disease. Influenza also has socio-economic consequences related to both direct and indirect healthcare costs, including hospitalisations, work absence and loss of work productivity when either a caregiver or child is sick with influenza.

Our focus

Our key marketed products

FluMist is the first live, attenuated nasally delivered vaccine approved in the US for the prevention of disease caused by influenza virus subtypes A and B in eligible children and adults, two to 49 years of age. Beginning in the 2009/2010 season, the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices in the US voted to expand recommendations for routine seasonal influenza vaccination to include all school-age children up to 18 years of age. In 2009, FluMist was approved for marketing in South Korea, Hong Kong and Israel. Applications are under review in Canada, Mexico and the EU. The total product supply of approximately 10 million seasonal FluMist doses sold out in 2009.

In response to the novel H1N1 influenza (swine flu) pandemic need in 2009, the US Department of Health and Human Services (HHS) awarded AstraZeneca a contract to develop and manufacture 42 million doses of influenza A (H1N1) 2009 monovalent vaccine. The total contract value is approximately $389 million. The monovalent H1N1 influenza vaccine, which is made using the same technology and process as FluMist, was approved by the FDA in September for the same patient population as FluMist. AstraZeneca began shipping product to the HHS in September.

In the pipeline

We continually strive to seek ways to improve our influenza vaccine. Each year we conduct clinical studies enabling us to develop and release a new vaccine for that year's influenza virus. In addition, we are investigating the potential of a quadravalent live attenuated influenza vaccine and have two studies for this underway.

Hepatitis C virus (HCV) infects an estimated 170 million people worldwide and the current market for HCV therapy exceeds $2 billion annually. However, therapy for the strains that predominate in the US and Western Europe requires 12 months' treatment and produces a durable cure in only 50% of patients. Key opinion leaders expect the current standard of treatment (interferon plus ribavirin) to change to a form of combination therapy involving one or more new mechanism of action direct-acting anti-virals and there are several small and large pharmaceutical companies with varying HCV pipelines focused on such therapies. A future paradigm of combinations of anti-virals as standard care offers the opportunity for several new therapies to be widely used.

Our focus

In the pipeline

Projects in development include AZD7295, a novel HCV compound, currently in Phase II.

Sepsis is a life-threatening condition resulting from uncontrolled severe infections, which affects an estimated three million people a year worldwide. Few industry pipelines are focused on the development of products specifically for registration for the treatment of sepsis or septic shock.

Our focus

In the pipeline

The development programme for CytoFab™, an anti-TNFα polyclonal antibody, our potential treatment for severe sepsis licensed from Protherics Inc. (now part of the BTG plc group), continues in Phase II development. CytoFab™ has the potential to be one of a limited number of medicines specifically developed for patients with severe sepsis.

Tuberculosis (TB) remains a worldwide threat and is newly diagnosed in over eight million people worldwide every year. It is one of the greatest causes of death from infectious disease in the developing world.

Our focus

As part of our commitment to make a contribution to improving health in the developing world, we are working to find a new, improved treatment for TB. We have a dedicated research facility in Bangalore, India that is focused on finding a treatment for TB that will act on drug-resistant strains, simplify the treatment regime (current regimes are complex and lengthy, meaning many patients give up before the infection is fully treated) and will be compatible with HIV/AIDS therapies (TB and HIV/AIDS form a lethal combination, each speeding the other's progress). Over 80 scientists in Bangalore are working closely with our infection research centre in Boston, US as well as with academic leaders in the field, and they have full access to all AstraZeneca's platform technologies, such as 'high throughput screening' and compound libraries. It is a complex area of research but a candidate drug, AZD5847, entered Phase I studies late in 2009.

Detailed information about material legal proceedings relating to our Infection products can be found in Note 25 to the Financial Statements.

Performance 2009

Reported performance

Total Infection sales increased on a reported basis by 7% to $2,631 million. H1N1 influenza vaccine sales were $389 million.

Performance - CER growth rates

Infection sales were up 10% at CER. This was driven by sales of $389 million for the H1N1 influenza vaccine to the US government and continued growth in Merrem/Meronem (5%) and FluMist (39%), which more than offset the 12% decline in Synagis sales.

Worldwide sales of Synagis in the fourth quarter were $401 million, a 21% decrease from the same period in 2008, driven by a decrease of 31% of US Synagis sales for the fourth quarter. This decline in the US is a result of the adoption of new guidelines published by the American Academy of Pediatrics restricting the usage of Synagis at the start of the 2009/2010 RSV season.

FluMist sales were $145 million for the full year.

Performance 2008

Reported performance

Total Infection sales increased on a reported basis by 43% to $2,451 million as a full year of Synagis and FluMist sales were taken in the Group for the first time, and Merrem/Meronem sales enjoyed another year of good growth.

Performance - CER growth rates

Infection sales were up 41% at CER.

For the full year, Synagis sales were $1,230 million. Synagis sales in 2007 were $618 million, but this only reflected sales since the acquisition of MedImmune in June 2007. Worldwide sales of Synagis in the fourth quarter were $506 million, a 5% increase over the same period in 2007 when the product was included in sales.

FluMist sales were $104 million for the full year. In contrast to 2008, all of 2007's FluMist sales of $53 million were realised in the fourth quarter as a result of the timing of regulatory approvals for the new formulation and expanded label.