AstraZeneca 20-F 2008
Documents found in this filing:
Legal & Secretary’s Department
15 Stanhope Gate
For the attention of Justin Hoskins
By fax 020 7304 5196 & by post
Dear Ladies and Gentlemen
IMS DATA DISCLOSURE FOR ANNUAL REPORT AND FORM 20-F INFORMATION 2007
In connection with the anticipated filing by AstraZeneca PLC (“AstraZeneca”) of certain registration statements with the US Securities and Exchange Commission, IMS Health hereby authorises you to refer to IMS Health and certain pharmaceutical industry data derived by IMS Health, as identified on the pages annexed hereto as Exhibit A, a selection of pages from AstraZeneca’s Annual Report and Form 20-F Information for the fiscal year ended 2007 (the “Annual Report”), which is incorporated by reference in the registration statements No. 33-83774 for AstraZeneca and Zeneca Wilmington Inc. and No. 333-145848 and No. 333-114165 for AstraZeneca, each on Form F-3, and in the registration statements No. 333-09060, No. 333-09062, No. 33-65362, No, 33-65366, No. 333-12310 No. 333-12426, No. 333-12428, No. 333-13328, No. 333-13918 and No. 333-124689 on Form S-8 for AstraZeneca. A copy of the relevant pages of the Annual Report has been provided to IMS Health.
Our authorisation is subject to your acknowledgement and agreement that:
IMS Health and certain pharmaceutical industry data derived by IMS Health;
Please indicate your agreement to the foregoing by signing in the space indicated below. Our authorisation will not become effective until accepted and agreed by AstraZeneca.
Very truly yours,
James E. Salltan. Vice President and Associate General Counsel, EMEA Region
For and on behalf of IMS Health
ACCEPTED AND AGREED
this 11th day of March 2008:
2007 was a transformational year for AstraZeneca and I am very proud of the way that my Senior Executive Team and all our employees are adapting to a challenging external environment and addressing the needs of our business.
Strengthening our pipeline continues to be our highest priority and we have made substantial progress over the past twelve months. We have also successfully delivered against our sales targets, whilst continuing to challenge all aspects of our cost base and drive productivity throughout the organisation.
The acquisition of MedImmune in June gave us a leading position in biologics technology and took us into vaccines for the first time. This was a very significant move for the Group. Increased investment in these approaches to fighting disease was key to our strategy of strengthening our ability to deliver the next generation of valued medicines. MedImmune is a leader in both biologics and vaccines and brings expertise and capabilities that span the pipeline from discovery through commercialisation. It is also a vertically-integrated company that has invested for future growth and gives us significant biologics and vaccines manufacturing capability and capacity. By combining our own biologics projects and those of Cambridge Antibody Technology under MedImmunes leadership, I believe we have created a powerful engine to drive future development.
Our key strategic priorities are:
Promoting a culture of responsibility and accountability is a fourth priority that underpins the other three.
As the industry changes and our business evolves, it is important that we have a workforce and style of leadership that can leverage opportunities and adapt quickly to changing circumstances. I believe that a lean infrastructure, combined with an agile mindset and a responsible approach to business, will be a critical success factor in determining our future.
STRENGTHENING THE PIPELINE
It is just as important to gain access to leading science from outside AstraZeneca and our externalisation programme has delivered over 20 major deals in the last two years, as well as the acquisitions of Cambridge Antibody Technology and MedImmune.
We also continue to partner with external organisations that share our commitment to finding novel solutions for important areas of healthcare. During 2007 we formed a number of important new collaborations, including one with Bristol-Myers Squibb Company to co-develop and co-commercialise saxagliptin and dapagliflozin, two products in development for the treatment of Type 2 diabetes.
We remain focused on leveraging the full potential of our range and delivered a growth in sales during 2007 despite pricing challenges in key markets in Europe and the US, where payers and healthcare providers have been wrestling with the dual challenge of a growing demand for healthcare as a result of the ageing population and continued public demand for the benefits that modern medicines provide.
Highlights in 2007 included:
In the emerging markets of Asia, Eastern Europe and Russia, we have continued to build our business focusing on maximising our sales today whilst investing to broaden access to our medicines in future. During the year, we opened a new Process R&D facility
in Bangalore, India, to add to the existing R&D facility and we are investing in a new centre for translational medicine in Shanghai, which will focus on researching medicines especially designed to help patients in China.
In Japan, the worlds second largest pharmaceutical market, we are working with the authorities to increase the range of medicines available to Japanese patients. Mutual recognition of research data generated in other Asian countries means that we are able to progress more quickly with dedicated studies for these markets.
Inevitably, as a successful, research-based pharmaceutical company, this year we have received further challenges to some of our patents, the details of which are set out elsewhere in this report. We will maximise the value of our intellectual property and will vigorously defend our patents in order to protect the many years of research, and the considerable investment, which have delivered the medicines to which those patents relate.
BECOMING LEAN AND AGILE
At the half-year, we announced further job reductions resulting from productivity improvements in other areas of the business. The full implementation of these reductions will take until 2009. However, they reflect important efficiency improvements including: the centralisation of clinical data management to a single approach managed at two locations; re-shaping the sales force in several European countries to be able to better respond to changes in the respective national healthcare systems; the establishment of a single, global contract with IBM for information technology services and support; and the globalisation of functions such as Human Resources and Regulatory Affairs.
Implementing changes that involve the loss of loyal employees is one of the hardest tasks for a Chief Executive Officer and 2007 has been particularly challenging in this respect. Throughout, we have consulted fully with staff representatives and acted in line with local labour laws. We have also provided appropriate support to help individuals to pursue their careers beyond AstraZeneca and have engaged with the communities around our affected sites to mitigate the local impact.
DOING BUSINESS THE RIGHT WAY
In 2007, we further strengthened our CR leadership and governance to make sure that we have appropriate systems in place for identifying the risks and opportunities associated with our CR, together with effective frameworks for managing them and driving compliance with all relevant policies and standards. As part of this, we reviewed and expanded our Code of Conduct to provide clear direction and guidance for all our staff on what is required of them. The new Code is being translated into over 40 languages and will be distributed to all our employees in early 2008. In addition, since the acquisition in June, we are working closely with MedImmune, which has its own long-standing commitment to working responsibly, to make sure that our policies and standards are aligned.
CR targets and measures are included in our business performance management framework and related objectives are being included in personal targets at all levels to support the integration of CR management across the full range of our business activities.
You can read about key aspects of our commitment to doing business the right way, and our performance, throughout this report and further details are provided on our website, astrazeneca.com/responsibility. We are making progress, but in the ever-changing world in which we live, there will always be work to do to ensure that AstraZeneca is not only valued as a source of great medicines, but also trusted for the way in which we do business worldwide.
SENIOR EXECUTIVE TEAM CHANGES
Whilst we cannot predict with precision what the next decade will look like for our business, we do know that the environment in which we operate will continue to present new challenges and opportunities. I am confident that AstraZeneca has the strategy, skills and resources that will enable us to anticipate, and adapt quickly and effectively to the changes that our business faces. Above all, our single-minded determination to succeed will ensure that we will continue to stay focused on our mission to deliver great medicines and a business performance that creates enduring value for our shareholders.
DAVID R BRENNAN
In this Business Environment section, unless otherwise specified, sector-wide market data (those data not specific to AstraZeneca or any of our products) are based on moving annual total (MAT) data for the third quarter of 2007, and the 2006 comparisons are based on MAT data for the fourth quarter of 2006.
GROWING DEMAND FOR HEALTHCARE
The demand for healthcare will be met not only by existing therapies but also by new ones originating from advances in both the understanding of the biology of disease and the application of new technologies. Innovative new products have been launched by the industry in recent years, which are both changing therapeutic approaches and improving the quality of life for patients.
In addition, fast-developing economies such as China and India continue to offer new opportunities for the industry to gain access to an expanding number of patients who can benefit from medicines. Pharmaceutical companies that are able to make efficient investment decisions, fully utilise their intellectual property and manage relationships with their stakeholders should be well positioned to benefit from the demand for healthcare and the new opportunities for the industry.
Europe accounts for 30% of the world market and experienced growth of 6% in 2007, up from 5% in 2006. Growth across major markets in Europe ranged from -1% in Italy to 10% in Spain, with Germany, France and the UK showing growth of 4%, 6% and 5%, respectively.
Asia Pacific and Latin America accounted for 7% and 4%, respectively, of worldwide sales. Notable growth from countries in these regions in 2007 came from China (sales of $13.1 billion, growth of 22%), Brazil (sales of $9.6 billion, growth of 10%), Korea (sales of $9.5 billion, growth of 10%) and India (sales of $6.4 billion, growth of 12%), which ranked ninth, 10th, 11th and 15th respectively in world markets.
BIOLOGICS AND VACCINES
Biological products are, in general, more complex to manufacture compared to small molecule drugs because they are effectively made by generating biological material from cells or other living tissue, rather than through the process of chemical synthesis used for small molecule pharmaceuticals. Essential for this biological manufacturing is a high degree of fermentation, purification and formulation expertise, which biotechnology companies have typically developed as a result of their work and investment over a number of years. The regulatory regimes for biosimilars or follow-on biological products (similar versions of existing biological products) are also far less developed than those for generic pharmaceutical drugs, although in Europe and increasingly in the US, formal paths leading to the approval of biosimilars are being evaluated by regulatory authorities. These factors can help produce longer product life cycles for biological drugs compared to traditional pharmaceutical products. Biopharmaceuticals typically have a higher success rate from when a biological drug is tested in man for the first time until it is approved for marketing. This is particularly the case up to the end of phase I development when biological drugs often have a more predictable pharmacokinetic and toxicity profile compared with small molecule pharmaceuticals at the same stage of development.
THERAPY AREA ENVIRONMENT
Our resources, skills and experience are focused on the following therapy areas, which together represent a significant proportion of the worldwide burden of disease:
In spite of effective treatments with PPIs, around 40% of patients do not achieve full relief from symptoms.
are significant differences in the pattern and severity of disease between Asian and Western populations. Whilst breast, prostate and colorectal cancers are common in the West, gastric and liver cancers are more prevalent in Asia.
Respiratory & Inflammation
Information about the medicines we have or are developing in the above disease areas and our 2007 product performance is set out on pages 50 to 68.
designed to be a selective and durable inhibitor of the DPP-4 enzyme, which regulates hormones that control plasma glucose levels. Phase III clinical trials to evaluate the efficacy and safety of saxagliptin are fully recruited. We plan to file a regulatory application for saxagliptin in the US in the second quarter of 2008. Results from a phase III trial were announced at the American Diabetes Association meeting in June 2007 and demonstrated that saxagliptin, when used as an add-on therapy to metformin, improved glycaemic control in adult patients with Type 2 diabetes, compared with the use of metformin alone, during 24 weeks of treatment.
Dapagliflozin is being studied as a once-daily oral anti-diabetic in the class of sodium-glucose contransporter 2 (SGLT2) inhibitors. Dapagliflozin is a selective SGLT2 inhibitor, and has the potential to be first in this novel class of anti-diabetics. It is designed to be used both as monotherapy and in combination with other therapies for Type 2 diabetes.
Phase IIa data presented at the 2007 American Diabetes Association meeting demonstrated that administration of dapagliflozin reduced fasting serum glucose in patients with Type 2 diabetes when administered for 14 days alone or concomitantly with metformin.
In addition to saxagliptin and dapagliflozin, we have compounds in the area of diabetes and obesity in the cannabinoid receptor inhibitor class, as well as glucose kinase activating compounds in early patient testing.
In April 2007, we terminated our licensing and collaboration agreement with AtheroGenics, Inc. for AGI-1067. AGI-1067, an investigational anti-atherosclerotic agent, was studied in the ARISE phase III clinical outcomes trial involving more than 6,000 patients with coronary artery disease, but the trial failed to meet its primary endpoint.
as drug plasma levels decline. AZD6140 is being developed to reduce the risk of thrombotic events in patients diagnosed with acute coronary syndromes (ACS). AZD6140 is currently being studied in the phase III PLATO clinical trial. This is a head-to-head outcomes study to determine if AZD6140 is superior to clopidogrel for reducing the risk of thrombotic events in patients with ACS. It is being conducted in over 40 countries at up to 1,000 investigational centres and will include approximately 18,000 ACS patients.
In anti-coagulation, our principal project is AZD0837, an oral, direct thrombin inhibitor in late phase II testing. An extended release formulation is being developed, giving the possibility to use once-daily dosing without significant peak-trough variability, in other words reduced variability in anti-coagulation effect throughout the dosing interval.
Global sales of Seloken/Toprol-XL fell by 22% to $1,438 million. US sales of the Toprol-XL product range, which includes sales of the authorised generic were down 30% for the full year, as the full range of dosage strengths were subject to generic competition from August 2007. Generic products accounted for 85% of dispensed prescriptions in the fourth quarter and the Toprol-XL product
range declined by 69% in that period compared with 2006. Sales of Seloken in other markets were up 5% for the full year as a result of growth in Emerging Markets.
Atacand sales in the US were unchanged for the full year whilst sales in other markets increased 12%.
Continued small declines were seen in Zestril (down 10% to $295 million) and Plendil (down 7% to $271 million), with general global falls compensated by increases in discrete markets.
Sales of Toprol-XL in the US were up 7% for the full year to $1,382 million. Total prescriptions in the US increased by 10% versus 2005. The November 2006 launch of Sandozs generic 25mg metoprolol succinate product in the US was followed by an announcement that we had entered into a supply and distribution agreement with Par Pharmaceutical Companies, Inc. to distribute an authorised generic version of the same 25mg dosage strength in the US market. As a consequence, adjustments were taken in respect of pipeline inventory in the marketplace with the effect that sales are now being recognised as prescriptions are written. Sales of Seloken in other markets were down 7% for the full year to $413 million.
Atacand sales in the US were up 12% to $260 million with new prescriptions up 7%. In other markets, Atacand sales were up 14% to $850 million.
Plendil sales were down 24% as a result of generic competition in the US market, where Plendil sales declined by 71% to $24 million.
We continue to have full confidence in our intellectual property protecting Nexium and will vigorously defend and enforce it.
Patients have benefited from over 889 million treatments with Losec/Prilosec (up to the end of October 2007) since its launch in 1988. Continued sales growth of Losec/Omepral was seen in Japan in 2007. Patent protection for omeprazole, the active ingredient in Losec/Prilosec, has expired (the first patent expiration was in Germany in 1999). We continue to maintain formulation patent property in respect of Losec/Prilosec. Further information about the status of omeprazole patents and patent litigation, including details of generic omeprazole launches, is set out in Note 27 to the Financial Statements on page 158.
Our appeal to the European Court of First Instance regarding the European Commissions Decision in 2005 to impose fines on us totalling 60 million ($75 million) for alleged infringements of European competition law relating to certain omeprazole intellectual property and regulatory rights is still pending. Further information about this case is set out in Note 27 to the Financial Statements on page 158.
Entocort is increasingly accepted as first-line therapy for mild to moderate, active Crohns disease and is approved in 44 countries.
For the full year, Losec sales declined by 20% to $1,143 million. Prilosec sales in the US were down 3% to $226 million. Losec sales in other markets were down 24%, although sales increased in Japan and China; sales in these two markets now account for almost 30% of the brands performance.
In the US, Nexium sales increased by 13% to $3,527 million. Dispensed tablet volume for Nexium increased by 17%; all other PPI class brands in aggregate declined by 4%. Nexium volume growth more than offset lower realised prices from contracted sales.
Sales of Nexium in other markets reached $1,655 million for the full year (up 10%) as good volume growth in France and Italy helped mitigate the significant price erosion in Germany. As a result, Europe sales improved by 6% to $1,166 million, whilst Asia Pacific revenues increased by 14% to $195 million, driven by Japan and China.
Losec/Prilosec sales were down 16% to $1,371 million. Prilosec sales were down 12% in the US and Losec sales in other markets were down 17%. Sales in Japan were up 7% at $227 million, whilst sales in China were flat.
For discontinued projects see page 30.
A phase III trial programme, which was initiated in the third quarter of 2007, is evaluating the incidence of gastric ulcers in at-risk patients with chronic pain taking PN400 versus the ulcer incidence in those taking naproxen alone. A regulatory submission for PN400 in the US is currently planned for the first half of 2009.
In October 2007, by mutual agreement with NPS Pharmaceuticals, Inc. we decided to end our collaborative efforts to discover and develop drugs targeting metabotropic glutamate receptors (mGluRs). As part of this agreement, we have acquired certain know-how, intellectual property and technology rights from NPS Pharmaceuticals for our exclusive use.
We have established a partnership with the University of Texas M. D. Anderson Cancer Center to develop platforms and clinical targets for new drugs in chronic pain.
AZD3480, the neuronal nicotinic receptor agent that we licensed from Targacept, Inc. in 2005, has successfully progressed into phase IIb clinical testing in both Alzheimers disease and cognitive disorders in schizophrenia (CDS). We have exercised a right to acquire an option from Targacept to take a licence of TC-5619, which Targacept is developing in CDS.
Zomig sales for the full year increased by 5% in the US (to $177 million) and 4% in other markets, totalling $434 million.
Seroquel sales reached $3,416 million (up 24%). In the US, Seroquel sales were up 24% to $2,486 million. Total prescriptions increased by 12%, well ahead of the market. The Seroquel share of total prescriptions in the US anti-psychotic market increased to 30.2% in December, up 1.7 percentage points over last year. In other markets, sales were up 23%, on good growth in Europe (up 25% to $619 million) and in Asia Pacific (up 15% to $149 million).
Zomig sales increased by 13% to $398 million. Zomig sales comparisons in the US for the full year as compared with 2005 are affected by the resumption of full responsibility from MedPointe, Inc. for US commercialisation in April 2005. Sales for Zomig in the US were up 39%, although total prescriptions declined by 6%. Sales of Zomig in other markets were unchanged.
2007 IN BRIEF
Iressa is used for the treatment of advanced non-small cell lung cancer (NSCLC) in patients who have failed chemotherapy. Following disappointing clinical trial data in 2004 from the ISEL study, in 2005 we voluntarily withdrew the European submission for Iressa and the regulatory authorities in the US and Canada restricted its use to those patients already benefiting from the drug.
In the third quarter of 2007, data from the phase III international INTEREST study comparing Iressa with docetaxel were reported. The study met its primary objective, demonstrating equivalent overall survival for Iressa and docetaxel in patients with pre-treated advanced NSCLC. This is the first time that a drug in this class has shown non-inferior survival to chemotherapy in a head-to-head study in this setting. In addition, Iressa demonstrated a more favourable tolerability profile and superior quality of life for patients compared with docetaxel. Based on these data, we are reviewing options for possible regulatory submissions.
Iressa continues to be marketed in the Asia Pacific region for pre-treated advanced NSCLC. It is currently being investigated in the first-line advanced setting in a large, phase III, pan-Asian trial known as the IPASS study. Further phase II trials are continuing to evaluate the potential benefits of Iressa in NSCLC and other EGF receptor-driven tumours.
Ethyol is used to help prevent certain unwanted side effects of specific types of chemotherapies and radiotherapies that are used to treat cancer. Ethyol was initially approved by the US Food and Drug Administration (FDA) in 1995 to reduce cumulative (kidney) toxicity associated with repeated administration of cisplatin to patients with advanced ovarian cancer. In 1999, the FDA approved the use of Ethyol for the reduction of the incidence of moderate-to-severe dry mouth (xerostomia) in patients undergoing post-operative radiation treatment for head and neck cancer, where the radiation port includes a significant portion of the parotid glands. Xerostomia, both acute and chronic, is a debilitating condition in which saliva production is reduced due to damage caused to the salivary glands by therapeutic radiation. We are the sole marketer of Ethyol in the US. Outside the US we have various distribution and marketing arrangements for the drug. Ethyol has been approved for marketing in 63 countries worldwide, including the US.
MedImmune is continuing the development of CAT-8015 with four phase I dose escalation studies in progress in chronic lymphocytic leukaemia, hairy cell leukaemia, CD22-positive non-Hodgkins lymphoma and paediatric acute lymphoblastic leukaemia. CAT-8015 is an immunotoxin that targets CD22, which is expressed on adult cells, B-cell leukaemia and lymphomas.
Casodex sales increased by 6% to $1,335 million. Sales in the US for the full year were up 1% to $298 million. Sales in other markets, which account for more than 75% of product sales, were up 8%, on 6% growth in Western Europe and 13% sales growth in Japan.
Iressa sales were unchanged for the full year. Sales in Japan increased 4% for the year; sales in China were up 24%.
Faslodex sales increased 10% to $214 million for the full year, on growth of 3% in the US and 18% sales growth in other markets.
In the US, sales of Arimidex were up 29% to $614 million. Total prescriptions increased by 21%. Arimidex share of total prescriptions for hormonal treatments for breast cancer was 37.5% in December, up 2.7 percentage points during the year. In other markets, Arimidex sales grew by 29% due to an increase in sales in Europe (up 30%) and Asia Pacific (up 27%) on strong volumes.
Casodex sales increased by 9% to $1,206 million. In the US, sales were up 23% to $295 million. Sales in other markets were up 5%, with sales in Japan up 10% to $286 million.
Iressa sales in markets outside the US increased by 10%. Sales in the Asia Pacific region were up 15% to $207 million.
Worldwide sales of Faslodex were up 32% to $186 million, largely due to the 74% increase in Europe. Sales in the US were up 12%.
Zoladex sales exceeded $1 billion for the second year in a row with declines in the US offset by growth elsewhere.
We have recorded alliance revenue of $18 million from our co-promotion arrangements with regard to Abraxane®.
The development of Symbicort pMDI for COPD and paediatric asthma in the US is on track, with regulatory submissions for both indications scheduled for the second quarter of 2008. Our existing regulatory filings for Symbicort pMDI in the EU for asthma and COPD are scheduled to be supplemented with data supporting two additional strengths in the second half of 2008.
A regulatory submission in Japan for Symbicort for the treatment of asthma in adults and adolescents (from 16 years and above) was filed in May 2007.
Our three-year partnership with Dynavax Technologies Corporation, which began in 2006, continues to pursue opportunities in the field of toll-like receptor 9 (TLR 9) for use in asthma and COPD. Dynavax has unique competence in generating immunostimulatory DNA sequences that activate TLR 9. The alliance should enable us to expand our portfolio of small molecule and biological drugs to treat asthma and COPD.
In February 2007, we announced a major discovery alliance with Argenta Discovery Limited aimed at identifying improved bronchodilators to treat COPD. A team of scientists from each company will collaborate in order to identify long-acting muscarinic antagonist (LAMA) and dual-acting muscarinic antagonist-ß2 agonist (MABA) candidate drugs.
In May 2007, we agreed to acquire the paediatric asthma business of Verus Pharmaceuticals, Inc., which includes the North American rights to CyDex Captisol enabled budesonide solution and a proprietary albuterol formulation. This deal also includes the North American rights to the agreement Verus Pharmaceuticals has with PARI, the German medical device company that makes eFlow, a novel nebuliser. The transaction will potentially allow us to provide patients and carers with new products that may be administered with a smaller, more portable nebuliser that could administer the medicine in less time than the current therapy, thereby improving treatment adherence in paediatric asthma patients.
In July 2007, we established an R&D collaboration with Silence Therapeutics plc, primarily in the respiratory field. The three-year collaboration is intended to discover and develop proprietary siRNA molecules against up to five specific targets provided by AstraZeneca. Silence Therapeutics and AstraZeneca will jointly collaborate in the early phase of identification and optimisation of novel siRNA molecules. We will retain full responsibility for clinical development and commercialisation.
Our early R&I small molecule pipeline includes novel compounds that target high unmet medical needs with a focus on COPD, but also asthma and musculoskeletal diseases. Compounds are in development for both oral administration and inhalation.
MedImmune is also carrying out a phase I study assessing the safety and efficacy of an anti-interferon-alpha treatment (MEDI-545), which has shown consistent evidence of clinical activity across multiple measures of disease in patients with mild-to-moderate systemic lupus erythematosus.
The first phase I study of CAM-3001 has been initiated to evaluate the safety and tolerability of single doses in patients with rheumatoid arthritis. CAM-3001 is a MAb targeting the alpha sub-unit of the granulocyte-macrophage colony stimulating factor receptor (GM-CSFR). The phase I study is the first clinical trial in which a MAb targeting GM-CSFR is being investigated in this population. During 2007, MedImmune acquired exclusive development rights to the CAM-3001 programme from CSL Limited.
Symbicort sales for the full year were up 22% to $1,575 million. Sales in Western Europe were up 16%, with market share up another point in the last 12 months, aided by the
rollout of the Symbicort SMART regime and growth from use in COPD. Good growth for the year was achieved in Canada (up 25%) and in Emerging Markets (up 26%). Sales in the US were $50 million since launch at the end of June 2007. Specialist physicians have rapidly adopted the product; nearly 75% of allergists and more than 60% of pulmonary specialists in our target audience have prescribed Symbicort. Share of new prescriptions for fixed combination products was 5.8% in the week ending 18 January 2008; market share of patients newly starting combination therapy is over 11.5%.
Pulmicort sales increased by 10% to $1,454 million. US sales increased 15% for the full year to $964 million. Pulmicort Respules sales in the US were up by more than 20% for the full year, on estimated volume growth of 15%. Of the approximately six million children under the age of eight who are treated for asthma, more than one million benefit from treatment with Pulmicort Respules. Sales in other markets were unchanged for the year.
Rhinocort sales fell by 4% to $354 million, with a 9% decline in the US being compensated by small gains elsewhere.
Sales of Symbicort increased by 18% to $1,184 million on continued market growth and share gains in Europe, where sales were $1,018 million. Sales in other markets reached $166 million.
Worldwide sales of Pulmicort were up 11% to $1,292 million. Once again, the primary driver for growth was Pulmicort Respules in the US, where sales were up 24%. Volume growth in the US was approximately 10%, with price changes, managed care rebate adjustments and inventory movements also contributing to the sales growth. Pulmicort sales in the rest of the world were $457 million.
Rhinocort sales were down 7% to $360 million, chiefly on sales of Rhinocort Aqua in the US market (down 9%).
Crestor continued its volume growth in 2007 despite generic pressure, with sales of $1,424 million. In November 2007, the FDA approved Crestor to slow the progression of atherosclerosis in patients with elevated cholesterol. This new indication is an important differentiator from other products in the cholesterol-lowering market. During 2007, Crestor prescription share continued to grow with cardiologists, whose patient population comprises a high proportion of patients with two or more risk factors, indicating that cardiologists understand and recognise the clinical benefits of Crestor. The entrance of generic simvastatin has had a major impact on the branded statin market, significantly greater than that seen in other therapeutic categories in similar situations in the past. We recognise that that there is a place for generics since they play an important role in health care economics, but we believe generics are not the best choice for all patients. As the market continues to evolve, we believe Crestor will continue to perform well in the changing environment and we remain committed to ensuring that appropriate patients have access to Crestor.
Atacand sales totalled $259 million on an underlying and reported basis.
In 2007, generic versions of the remaining three strengths of Toprol-XL were launched. At the same time as the generic entries, we announced that we had expanded our previously announced supply and distribution agreement with Par Pharmaceutical Companies, Inc.. Par began distribution of an authorised generic version of the 50, 100 and 200mg dosage strengths of metoprolol succinate extended-release tablets in the US. Par had begun distributing a 25mg authorised generic of metoprolol succinate in November 2006. In an appeal to a previously reported patent decision, the Federal Court of Appeals for the Federal Circuit upheld the lower court decision regarding double patenting but reversed the decision relating to unenforceability. We requested reconsideration of this decision, but this was denied.
Arimidex continued to perform well with sales up 13% (+13% reported) to $694 million for the full year. Arimidex continues to be the market leader in total and new prescriptions for hormonal treatments for breast cancer in the US market.
Pulmicort Respules, the only inhaled corticosteroid for the treatment of asthma approved in the US for children as young as 12 months, has experienced strong sales growth of 22% over the previous year. In October 2007, a new 1mg strength was launched to provide physicians with an additional option to control paediatric asthma.
Symbicort pMDI was launched in the US in June 2007 to specialists, and in July 2007 to primary care physicians. For the week ending 18 January 2008, Symbicort achieved an overall new prescription (NRx) share of the inhaled corticosteroid/long-acting beta-agonist market of 5.8%. Among allergists, the NRx share was 12.1% of that market. Aided awareness amongst all targeted physicians is high and a broad base of prescribers is being built with more than 30,000 physicians now having used Symbicort. More than 10% of patients who are new to combination therapy have been prescribed Symbicort.
In October 2007, the FDA approved the actuation counter for the Symbicort pMDI and we plan to launch this in the US in the second half of 2008. The paediatric and COPD trials for Symbicort pMDI are on track to support the sNDA submissions planned in the first half of 2008.
In the US, the passage of the FDA Amendments Act (FDAAA) in September 2007 has a potentially wide-ranging impact on the industry. In addition to re-authorising the Prescription Drug User Fee Act, the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act, the FDAAA contains a number of provisions that substantially increase the authority and enforcement options of the FDA, including but not limited to expanded authority regarding pharmacovigilance, post-marketing safety surveillance, clinical trial registration and results posting and review of direct-to-consumer advertising.
Medicare Part D prescription
patient access approach to Medicare Part D contracting, our inclusion on Medicare Part D formularies continues to be strong, allowing a large segment of the patient population access to our medicines.
Although Medicare Part D to date has had a limited effect on pricing in the broader US market, it is difficult to predict fully the longer-term effects of this initiative on our business. Pressure on pricing and access is, however, generally increasing in the US, driven, for example, by an increased focus on generic alternatives. Primary drivers of increased generic use are budgetary policies within healthcare systems and providers and changes in pharmaceutical benefit design.
We continue to support My Medicare Matters, the community based outreach and education programme, in partnership with the National Council on Aging (NCOA). In 2007, My Medicare Matters and AstraZeneca received several awards. These included the NCOA Arthur Fleming Award for Public-Private Partnership, given for the first time to a pharmaceutical company, and the Silver Anvil Award, sponsored by the Public Relations Society of America, for a public relations campaign supporting public service partnerships. Activities in 2007 included demonstration grants to nine community-based organisations piloting innovative and effective outreach strategies to low-income-subsidy beneficiaries and enhancements to the award winning MyMedicareMatters.org website, as well as launch of an online community for professionals.
We maintained our market position as the second largest brand name pharmaceutical company in Canada. Crestor maintained its number two ranking in the statin market and was the fastest-growing product in both new and total prescription segments (39% and 44% growth respectively). Sales growth was supported by the Crestor Healthy Changes Support Program, which helps patients to understand better and improve the management of their cholesterol and to develop a healthier lifestyle.
Seroquel remains the leader in new and total prescriptions within the atypical anti-psychotics market. Atacand continues to outperform the anti-hypertensive market, with new prescription growth of over 15%, compared with market growth of only 5%.
Several key regulatory approvals were achieved in Canada in 2007. Seroquel XR was approved for the management of manifestations of schizophrenia. Nexium received several key regulatory approvals including two paediatric indications (ages one to 11 years and 12 to 17 years), an on-demand indication and finally an indication for Zollinger-Ellison syndrome. Symbicort Turbuhaler and Oxeze Turbuhaler received competitive class-labelling updates to incorporate recent long-acting beta-agonist safety information.
REST OF THE WORLD
of the world
Overall our sales in France ($1,794 million) were maintained at the same level as 2006. We saw good sales growth for our primary care brands Crestor (underlying +41%, +54% reported) and Symbicort (underlying +6%, +16% reported), each of which gained significant market share from competitors.
In Germany, sales of $1,233 million were down 3% (+6% reported), mostly due to the roll-over of last years government interventions. Most affected was Nexium (underlying -17%, -9% reported) where price pressure and drive for generic prescription remained high. Symbicort, however, for the first time achieved value market leadership (15% underlying growth, +26% reported) with 42% of the market for fixed combination long-acting beta-stimulants and inhaled corticosteroids. Seroquel continued to grow well with 13% underlying growth (+24% reported) reaching 20% of the market for atypical anti-psychotics.
In the UK, sales were $1,004 million (up 8%, +18% reported), driven by Crestor (underlying +7%, +18% reported), Symbicort (underlying +42%, +55% reported), Seroquel (underlying +12%, +22% reported), and Arimidex (underlying +15%, +25% reported). Many of our other brands also performed well with Merrem (+32%, +46% reported) being of particular note. Competition in the market remained intense but our key brands gained market share in their respective segments. Especially strong were Seroquel and Symbicort achieving gains of two and one percentage points respectively. The UK Government and pharmaceutical industry have entered into terms of reference discussions concerning potential changes to the pricing and reimbursement scheme. Negotiations are expected to be completed in 2008.
In Italy, Crestor and Symbicort increased the sales by 16% (+27% reported) and 3% (+13% reported) respectively while speciality care brands also enjoyed healthy rises with Seroquel increasing the sales by 6% (+16% reported) with 19% of the market for atypical anti-psychotics and Arimidex increasing sales by 8% (+18% reported) with 53% of the market for aromatase inhibitors and tamoxifen. However, overall sales declined by 6% (+2%
reported) to $1,294 million as a result of reference pricing at the regional level on PPIs and measures to control their prescribing by physicians. Nexium sales fell by 24% (-17% reported) and Losec by 37% (-31% reported).
In Spain, sales of $868 million were driven by Nexium (+46%, +60% reported), Symbicort (+17%, +28% reported) and Seroquel (+21%, +32% reported), whilst Arimidex and Casodex maintained a high share of their respective markets.
A summary of government cost-containment measures in Europe and their impact on our business can be found on page 32.
Synagis sales outside of the US are undertaken on our behalf through a subsidiary of Abbott Laboratories based in The Netherlands. Revenue from this arrangement amounted to $169 million. We estimate that about 40% of the underlying sales arise in Western Europe, about 35% in Japan and over 10% in Canada. Strong growth has been recorded in Latin America in 2007.
There has been a positive move towards the acceptance of non-Japanese Asian data as part of the regulatory approval package for Japanese patients. The Ministry of Health, Labour and Welfare (MHLW) has established a study team, with a remit to propose basic policies for the mutual acceptance of clinical data from Korea, China and Japan within the next two to three years. In addition, MHLW guidance issued in September 2007 facilitates earlier participation by Japan in international clinical studies.
Other Established rest
of the world
Emerging rest of the
Emerging Asia Pacific
Strong growth was seen in India, Indonesia, Malaysia, Singapore and Vietnam, where market dynamics continue to be positive.
In the Philippines and Thailand an uncertain market environment slowed our growth.
This is the result of the investment made to develop our key products in fast-growing markets. Nexium, Seroquel, Crestor and Symbicort all showed strong performance with overall sales of $303 million, which is up 48% versus last year (56% reported). Nexium is our number one prescription product in Latin America with overall sales of $144 million (up 49%, 54% reported). Crestor is now the number four prescription product with overall sales of $84 million (up 40%, 47% reported).
Mexico continued to be our largest market in the region, with sales of $334 million (up 17%, +17% reported). Our share in the prescription market moved up to 4% and we moved up to the number nine position in the rankings.
In Brazil, sales were $330 million with an underlying growth of 19% (+33% reported). The best-selling brand was Zoladex with sales of $47 million, followed by Crestor with sales of $35 million and Nexium with sales of $31 million. Our share in the prescription market in Brazil maintained 3% and we moved up to the number 10 position in the rankings.
Middle East and Africa
gastro-oesophageal reflux disease (GERD)
A condition where gastric juices, containing acid, travel back from the stomach
into the oesophagus.
line extension A new formulation, indication or presentation of a marketed product.
new chemical entity (NCE)
A new, pharmacologically-active chemical substance. The term is used to differentiate
from line extensions and existing drug products.