EX-15.5 10 a19-3601_1ex15d5.htm EX-15.5

Exhibit 15.5

 

AstraZeneca PLC

Legal & Secretary’s Department

1 Francis Crick Avenue

Cambridge Biomedical Campus

Cambridge CB2 0AA

 

For the attention of Adrian Kemp

By email & by post

 

March 5, 2019

 

Dear Ladies and Gentlemen

 

IQVIA DATA DISCLOSURE FOR ANNUAL REPORT AND FORM 20-F INFORMATION 2018

 

In connection with the anticipated filing by AstraZeneca PLC (“AstraZeneca”) of a Form 20-F with the U.S. Securities and Exchange Commission, IQVIA Solutions HQ Limited (“IQVIA”) hereby authorizes AstraZeneca to refer to IQVIA and certain pharmaceutical industry data derived by IQVIA, as identified (highlighted in yellow) on the pages annexed hereto as Annex A, a selection of pages from AstraZeneca’s Annual Report and Form 20-F Information for the fiscal year ended December 31, 2018 (the “Annual Report”), and the sixth  sentence in the fifth paragraph under the heading “Item 4. Information on the Company—Business Overview—Geographical Review—2017 in brief” and the third sentence in the fourth paragraph under the heading “—2016 in brief” in this Form 20-F dated March 5, 2019, each of which is incorporated by reference in the registration statement No. 333-214756 for AstraZeneca on Form F-3, and in the registration statements No. 333-226830, 333-216901, No. 333-170381, No. 333-152767, No. 333-124689 and No. 333-09062 on Form S-8 for AstraZeneca.

 

IQVIA’s authorization is subject to AstraZeneca’s acknowledgement and agreement that:

 

 

1)  IQVIA has not undertaken an independent review of the information disclosed in the Annual Report other than to discuss our observations as to the accuracy of the information relating to IQVIA and certain pharmaceutical industry data derived by IQVIA;

 

2)  AstraZeneca acknowledges and agrees that IQVIA shall not be deemed an “Expert” in respect of AstraZeneca’s securities filings, and AstraZeneca agrees that it shall not characterize IQVIA as such; and

 

3)  AstraZeneca accepts full responsibility for the disclosure of all information and data, including that relating to IQVIA, set forth in the Annual Report as filed with the SEC and agrees to indemnify IQVIA from any third party claims that may arise therefrom.

 


 

Please indicate your agreement to the foregoing by signing in the space indicated below. Our authorization will not become effective until accepted and agreed by AstraZeneca.

 

Very truly yours,

 

/s/ James E. Salitan

 

 

James E. Salitan

Vice President and Associate General Counsel,

For and on behalf of IQVIA Solutions HQ Limited

 

ACCEPTED AND AGREED

 

This fifth day of March 2019

 

AstraZeneca PLC

 

/s/ Adrian C N Kemp

 

 

Name: Adrian C N Kemp

Title: Company Secretary

 


 

A changing world > NCDs kill41 million people each year, disproportionately affecting low-and middle-income countries > Growing and ageing populations, with increasing urbanisation > Breakthroughs in digital and other technologies transforming the pharmaceutical industry Increasing demand for healthcare > The USis the largest pharmaceutical market, with 47% of global sales > Pharmace\ltic sale growth of 4.4% in 2018, led by emerging markets > Expected growth to 2022 will be led by the US and developing markets but with slower growth in China Pharmaceutical sector opportunities and challenges > Pricing, regulation and patent exclusivity present opportunities as well as challenges Society is changing $47tn The WHO estimates that NCDs kill41 million people each year and could cost the global economy $47 trillion by 2030. Increasing burden of chronic disease An ageing population and changes in soctety are contnbuting to steady increases in non-communicable diseases (NCDs) with developing countries particularly affected as their populations grow. As the burden of NCDs grows, so do public expectations while governments' ability to meet them is constrained as finances are under stress.Low­ and middle-income countries are also disproportionately affected by issues such as air pollution and climate change, thereby exacerbating social, economic and demographic inequalities. 75°/o NCDs disproportionately affect people in low-and middle· income countries where more than three quarters of global NCO deaths -32 million -occur. Growing societal expectation of businesses Society's views of business are changing with organisations no longer valued solely on the quality of products and services and financial performance, but also thetr engagement with employees, customers, communities and society as a whole.Workforce dynamics are also changing for many as working for a single employer is replaced by working independently in a number of different roles. 57°/o Between 2001and 2020, the WHO estimates that chronic diseases will have increased by 57%. 11 A.straZeneca Annual fUport & Form 20-F Information 2018/ Marketplace > The sector is reshaping itself at the same time as it seeks to develop trust with key stakeholders A changing world

 

I 2• "'' ", g• Increasing demand for healthcare Global pharmaceutical sales As shown in the c hart on the ri ht local pliarmaceutica sales grew by 4.4% in 2018 2018 2017 2016 2018 2017 2016 stablished Markets saw a average revenue increase o 3.9% and Emerging Market evenue grew at 6.4%. The U China, Japan, Germany and France are the world's top five harmaceutical markets by 2018 1/ Dtnotes a scale break. Data based on worldmarkesales using AstraZenmarketdefinitions as set oot in the Marketdefinitionson page 239. Sowce: JQVIA, IQVIA Midas Quantum Q3 2018 (including US data}. Reported values and growthare based onCER. Value figures are rounded to the nearest billion and growth percentagesare rounded to the neare•t tenth. sales. In 2018, the US had 4 of global sales 2017' 47.2% : 47.7°!. ''''(mj' $2llbn Estimated pharmaceutical sales and market growth-2022 The table on estimated pharmaceutical sales and market growth to 2022 on the right also illustrates that we expect the established markets in North America and developing markets, inclucling Africa, CIS, Indian subcontinent and Latin America, to fuel pharmaceutical rowth.Market growth in China: orth Oilier Europe Non-EU countries ·· · .§5.biii. •.#&¥§). 5.410 Oceania . ......................... i$i§.il ..... .. .. .. .. .. [ 1.5% 1.1% ·s expected to remain belo historical levels at a compound annual growth rate of 4.6%. This ·s due to the continued slow.,... .., of the rna·or os ita!sector -·-·-·-·-·-··-··· .-.....-. . 8.. .. -----............a...o.. .. Iestimated pharmaceutical $8IU-2022. Data is based on ex·manufacturer prices at CER.Sowce: JQVJA. estimated pharmaceutical market growth. Data is based on the compound annual growth rate from 2017 to 2022. ............... CMlddle EaSi) ····· ••·•·••·•·••·•·••·•·••·•·•• I§ W. Sourc e:IQVIA. 13 AstraZeneca Annual Report & Form 20·F Information 2018/ Marketplace 2018 2017 2016 2018 2017 2016

 

Marketplace continued Pharmaceutical sector opportunities and challenges In addition to the global trends set out on the previous pages, we also face a number of opportunities and challenges within the pharmaceutical sector, as set out below. Our strategy reflects our response to this environment and, where applicable, the relevant strategic response to each trend is highlighted below. [0 Potmore mformalion,SC(! Strategy from page 18, Key Performance Indicators from page 20, Achieve Scientific Leadership from page zs.Return to Growth frompage 29 and Be a Great Place to Work frompage 38. Advances in science and medicine Scientific innovation is critical to addressing unmet medical need.Thedelivery of new medicines will rely on a more advanced understanding of the underlying biology of the disease, and the use of new technology and approaches. These include genomics and digital healthcare.Scientific and technological breakthroughs in small molecules and in biologics are also helping accelerate innovation. Innovation will be accelerated through the use of large volumes of biological data from disease biology and genomics which is driving precision medicine, while advances in data management and data integration are improving the speed and quality of clinical trial processes. Such advances have resulted in increased numbersof FDA Priority Reviews and Breakthrough designations. e cost of developmg new medicmes continues t rise with annual global R&D investment estimate $1 illi n Regulators and payers are demanding greater evidence of the comparative effectiveness of medicines. On the other hand, a greater emphasis on Proof of Concept is helping to improve productivity and reduce costs by showing the potential efficacy of drugs earlier in the development process. gainst this background, 59 The FD:oaApp_r_ove-.d-c59'""nov"e"l" drugs in 2018 compared witli 46 in 2017 and 22 in 2016. the FDA approved 59 novel drugs in 2018 com with 46 in 201 and 22 in 2016.Nevertheless, the e risk of any products failing at the development or launch stages, or not securing regulatory approvals, continues. Link to strategy 0Achieve Scientific Leadership CD Formoreinformation, see Ri..sk f:rompage 220. Regulatory environment "We believe that transparency enhances the scientific understanding of how our medicines work and is in the medical interest of our patients." The public's expectation of safe, effective and high·quality medicines is reflected in a highly regulated biopharmaceutical industry. At the same time, weare seeing instances of government policy and regulation being introduced to stimulate innovation in drug development, and of regulatory health authorities implementing programmes intended tospeed up patient access to transformative medicines. Examples include the 21st Century Cures Act of 2016 and the FDA Reauthori2ation Act of 2017 in the US, a new conditional early approval system in Japan and proposed changes to regulations in China. The implementation of the EU Clinical Trials Regulation has also been delayed. Nevertheless, paediatrics and use of digital tools in clinical development, as well as patients'access to innovative medicines and stakeholders' interactions to improve drug development, are high on the EU agenda. In biosimilar development, regulatory requirements for the registration of biosimilar products are becoming better defined. However, significant areas of regulatory policy are still evolving. Among these are transparency of data regarding the level of evidence to support approval of claims for biosimilarity in labelling, standards lor interchangeability and pharmaceutical substitution, and traceability of pharmacovigilance reports through naming conventions that permit differentiation of products. In addition, international harmonisation of regulatory requirements is being advanced in many areas through organisations such as the International Council for Harmonization ([CH), the Pharmaceutical Inspection Cooperation Scheme (PIC/S), the Pan American Network lor Drug Regulatory Harmoni2ation (PANDRH), and the International Conference of Drug Regulatory Authorities (ICDRA). Increased transparency of data used for regulatory decision making continues to be an area of interest to regulatory authorities in the EU and the US. It has recently attracted interest elsewhere, such as in Canada. We believe that transparency enhances the scientific understanding of how our medicines work and is in the medical interest of our patients. There are also uncertainties. In Europe, they include how the UK will work with the EU regulatory system following its planned exit from the EU, the approach the UK will take to establishing its own regulatory system outside the EU, and the relocation of the EMA from London to Amsterdam, Netherlands (and the likely disruption this will cause to regulatory processes). Link to strategy 0Achieve Scientific Leadership [0 For more information,see Rl.sk frompage 220.Por more mfonnationabout biosimilars, see Loss: of exclusivity and generictsationopposite. 14 AstraZeneca Annual Report & Form 20-F fnformation 2018/ Strategic Report

 

I 2• "'' ", g• Pricing of medicines "We continue to see examples where healthcare services (including pharmaceuticals) are highly regulated by governments, insurers and other private payers through various controls on pricing and reimbursement." Pricing and reimbursement remain challenging in many markets. We continue to see examples where healthcare services (including pharmaceuticals) are highly regulated by governments, insurers and other private payers through various controls on pricing and reimbursement. Implementation of cost-containment reforms and shifting market dynamics are further constraining healthcare providers, while difficult economic conditions burden patients who have out·of·pocket expenses relating to their medicines.Pharmaceutical companies are now expending significant resources to demonstrate the economic as well as the therapeutic value of their medicines. Pricing controls and transparency measures remain a priority in key markets such as China, where the National Reimbursement Drug List (NRDL) was updated in 2017. In Europe, governments continue to implement and expand price control measures for medicines, and the EU has committed to introducing a harmonised HTA review. In other markets, there has been a trend towards rigorous and consistent application of pricing regulations, including reference pricing and group/alliance purchasing. There is also pressure on pricing in the US.For example, federal and state policymakers are considering legislative and regulatory efforts to lower drug prices and to implement transparency measures. While legislative efforts to repeal and replace the Affordable Care Act (ACA) have not been successful, the current administration and members of Congress remain focused on healthcare policy priorities, including efforts to increase competition and generic drug use in government programmes, which could create downward pressure on pricing. The healthcare industry may also be used as a means to offset government spending. US federal agencies continue to propose and implement policies and programmes with the goal of reducing costs, increasing transparency, transforming the delivery system, and improving quality and patient outcomes. The need and desire for payers to manage drug expenditure has been heightened by the shift over the last decade from a primary care to a specialty care focus.Specialty drugs are used for the treatment of complex, chronic or rare conditions such as cancers, and pricing for these products reflects the higher value they bring to patients and payers, as well as the smaller patient numbers as a result of targeted treatment options. Link to strategy 0Return to Growth [)] for more information,sec Risk from page 220. Loss of exclusivity and genericisation Patent protection for pharmaceutical products is finite and, after protection expires, payers, physicians and patients gain greater access to generic alternatives (both substitutable and analogue) in many important drug classes. These generic alternatives are primarily lower priced because generic manufacturers are largely spared the costs of R&D and market development. Biologics typically retain exclusivity for longer than traditional small molecule pharmaceuticals, with less generic competition. With limited experience to date, the substitution of biosirnilars for the original branded product has not followed the same pattern as generic substitution in small molecule products and, as a result, erosion of the original biologic's branded market share has not been as rapid. This is due to biologics'complex manufacturing processes and the inherent difficulties in producing a biosimilar, which could require additional clinical trials. However, with regulatory authorities in Europe and the US continuing to implement abbreviated approval pathways for biosimilar versions, innovative biologics are likely to face increased competition. Like biologics, some small molecule pharmaceutical products are in complex formulations and/or require technically challenging manufacturing and thus may not follow the pattern of generic market erosion seen with traditional, tableted pharmaceuticals. For those products, the introduction of generic alternatives (both substitutableand analogue) can beslower. 84.8°/o or prescriptions"d'is.'p,.e"n'"s""e""' in the US in 2018, generics constituted 84.8% of the market y olume (2017: 84.9% . As a result, demand for generics is high. o rescriptions dispensed in the US in 2018 enerics constituted 8 Jll.lW:JiliS1JW..Q olume 2017·84.9% . Generic competition can also result from patent disputes or challenges before patent expiry. Increasingly, generics companies are launching products 'at risk', for example, before resolution of the relevant patent litigation. This trend, which is likely to continue, creates significant market presence for the generic version while the litigation remains unresolved. Given the unpredictable nature of patent litigation, some companies have settled such challenges on terms acceptable to the i nnovator and generic manufacturer.While competition authorities generally accept such agreements as a legitimate way to settle these d isputes, they have questioned some settlements as being anti-competitive. Link to strategy eReturn to Growth [0 For more mformation, see lnteJlectual Property from page 3S. 15 AstraZeneca Annual Report & Form 20·F Information 2018/ Marketplace

 

Business Review Return to Growth continued Regional Product Sales 1. EmergingMarkets 3.Europe ?2C .:::. 12°/o in the year :!!!1:£! .!!iir r 12% growth in the year a.!:..:.::&: (13%at CER) to $6,891m 2. us 11°/o 11% growth in the year (11% at CER) to $6,876m (10% at CER) to $4,459m .:!Eli!!!!!:. •.a=a:-=ia: iii= ·:::.· D . ·; 4.Established Rest of World (8)0/o 8% decline in the year {9% at CER) to $2,823m AU numbers asat 31 December 2018. us Pricing and delivering value Our medicines help treat unmet medicalneed, improve health and create economic benefits. Effective treatments can lower healthcare costs by reducing the need for more expensive care, preventing more serious and costly diseases and increasing productivity. We are committed to a pricing policy for our medicines based on four principles: > We pursue a flexible pricing approach that reflects the wide variation in global healthcare systems. We have developed patient access programmes that are aligned with the ability to pay of patients and healthcare systems. We are committed to the appropriate use of managed entry schemes and the development of real-world evidence and we are investigating innovative approaches to the pricing of medicines, such as payment for outcomes received by the patient and healthcare system. tile s1xteentli largest prescrgi lion-as. 'e"-­ (pharmaceuticalcompany in the US, we have a (?. '1'9 market share of US pharmaceutical Gaie§ valueln 2018, Product Sales in the US increased by 11% to $6,876 million (2017:$61, 69 million). The US healthcare system is complex with multiple payers and intermediaries exerting pressure on patient access to branded medicines through regulatory and voluntary rebates.Regulatory rebates are statutorily mandated chargebacks and discounts paid on government-funded programmes such as Medicaid,Department of Defense (including TRICARE) and Department of Veteran's Affairs. Voluntary rebates are paid to managed care organisations and pharmacy benefit managers for commercially insured patients, including Medicare Part D patients.In the Medicare Part D programme, in addition to voluntary negotiated rebates, branded pharmaceutical manufacturers are statutorily required to pay a percentage of the patient's out-of-pocket costs during the ·coverage gap' portion of their benefit design.From the beginning of 2019, the mandatory coverage gap discount increased to 70% from its fonmer amount of 50%,as a result of the passage of legislation in 2018. As part of the Affordable Care Act {ACA),we also pay a portion of an overall industry Patient Protection and Affordable Care Act Branded Prescription Drug Fee. > We determine the price of our medicines while considering their full value for patients, payers and society. The agreement on price involves many national, regionaland local stakeholders, reflecting factors such as clinical benefit,cost effectiveness,improvement to life expectancy and quality of life. > We aim to ensure the sustainability of both the healthcare system and our researchl·ed business model. We believe we share a collective responsibility with healthcare providers and other stakeholders to work together to enable an efficient healthcare system for patients today and support a pipeline of new medicines for patients tomorrow. > We seek to ensure appropriate patient access to our medicines. We work closely with payers and providers to understand their priorities and requirements, and play a leading role in projects to ailgn better the requirements of regulatory and health technology assessment (HTA) agencies or other organisations that provide vaul e assessment of medicines. For example, we have a leading rolein the European IMI ADAPT-SMART programme for exploring adaptive licensing. By way of example of our approach, we apply Tiered Pricing Principles globally. This defines price levels commensurate with affordability based on a country's ability to pay. We believe that this approach to pricing is sustainable and fair, and that it will increase access and improve patient outcomes in Emerging Markets. More generally, we remain committed to exploring innovative solutions to improve patient access and affordability, focusing on the value our medicines bring to patients and the healthcare system.We are collaborating with payers to conclude value-based pricing solutions that improve patient outcomes and have entered into 37 such agreements across our therapy areas.For more information,see the case study on page 17. In 2018,the overall measurable reductionin our prof t before tax for the year due to discounts on branded phanmaceuticals in the Medicare Part D Coverage Gap and anindustry-wide HealthCare Reform Fee was $432 million(2017: $119 mlilion;2016;$471million). 30 AstraZeneca Annual Report & Form 20-F fnformation 2018/ Strategic Report

 

I 2• "'' ", g• Established Rest of World (ROW)' In 2018,Product Sales in Japan decreased by 9% at actual rate of exchange (11% at CER) to $2,004 million (2017: $2,208 mlilion), as a result of the biennialgovernment price cuts and increased intervent on from the government to rapidly increase the volume share of generic products.Qii.SOe tejjj6e("201(jjere£i® uthorised generic entered the market an ·n cember 2017 we saw more tha g n ric c rumies enter thpw;;e;s:;:e:;s"t '"t"i"j"jl market with generic rosuvastatin which ha strongJyJmpacted Crestor Product Sale with a decrease of 60%.Leaving aside these generic restraints, a(:!an is presenting stron growth from the brands in our Growl (Piat!Qijjj§)and Nexium. In addition,there were particularly strong performances from Tagrisso,Fasenra, tmfinzi, Lynparza and the Diabetes franchise. e now old twel (ijOSitionin the ranking of pharmaceutic 9mpanies by sales of medicines in,)Man at::>an remains an attraclil! e market foq In the US,there is signif cant pricing pressure driven by payer consolidation, restrictive reimbursement policies and cost controltools. such as exclusionary formularies and price protection clauses.Many formularies,which specify particular medicines that are approved to be prescribed in a healthcare system,or under a healthinsurance poilcy,employ 'generic first' strategies and/or require physicians to obtainprior approval for the use of a branded medicine where a generic alternative exists. These mechanisms canbe used by intermediaries to limthe use of branded products andput pressureonmanufacturers to reduce net prices.In 2018 84.8% o We understand that our medicines will not benefit patientsif they are unable to afford them and that is why we offer a number of resources and programmes that can help increase patients' access to medication and reduce their out-of-pocket costs. We focus our formulary access on affordability for patients through rebate payments as well as savings cards for eligible patients when the out-of-pocket costs are not affordable. AstraZeneca has one of the longest-standing patient assistance programmes in the industry, AZ&Me,which provides eligible patients with AstraZeneca medicines at no cost. AstraZeneca has provided prescription savings to four million patients across the US and Puerto Rico over the past 10 years. rescriptions dispensedin the, US we@Jleneric with 84.9% in 201 In add ion, patients are seeing changes in the design of their health planbenefits andmay experience variation, ncluding increases,in both premiums and out-of-pocket payments for their branded medications. The pat ent out-of-pocket spend is generally in the form of a co-payment or co-insurance,but there is a growing trend towards high-deductible healthplans which require patients to pay the fulllist price untilthey meet certain out-of-pocket thresholds. [!] Formore informahon, see Community mveatment on page48. Europe The totalEuropean pharmace uticalmark et; o h $196 billionin 2018. We are the · ee Oargest_prescription-basedpharmaceuti mpanyin Europe (see Market definiot innovative harmaceuticals Canada has a mixed public/private payer system for medicines that is funded by the provinces, insurers and individual patients. It has also now become common for public payers to negotiate lower non-transparent prices after they have gone through a review by the Canadian Agency for Drugs and Technology in Health, a health technology assessment body.Most private insurers pay full price,although there is increasing pressure to achieve lower pricing. Overall,the split for AstraZeneca's portfolio is 62% funded by private payers and 38% by public plans. am_page 239) ith a 2.0% market shar harmaceutical sales bval ue. o Ongoing scrutiny of the US pharmaceut cal industry, focused largely on pricing,has been the basis of multiple policy proposals in the US.In May 2018, the Trump Administrat on issued its 'Blueprint to Lower Drug Pr ces and Reduce Out-of-Pocket Costs', which included a wide range of policy proposals that would impact the US pharmaceuticalindustryif implemented. Proposed changes under consideration include,but are notlimited to, fundamentally changing the role of rebates in the pharmaceutical supply chain,reforms to the 3408 Drug Pricing Program,and policies to increase competit on in the Medicare programme and encourage generic drug use. The Trump Administration has already taken action on several of the policies discussed in the Blueprint, and more policy actions are pending.In addition, lawmakers at both the federal and state level have sought increased drug pricing transparency and have proposed and implemented poilcies thatinclude measures relating to the submission of proprietary manufacturer data,establishment of price parameters that are indexed to certain federalprogrammes. and reporting of changes in pricing beyond certain thresholds. In 2018, our Product Sales in Europe decreased by 6% at actualrate of exchange (10% at CER) to S4,459 million (2017:$4,753 million).Key drivers of the decline,leaving aside theimpact of divestments such as Seloken, Atacand,Nexium and Zomig, were cont nued competition from Symbicort analogues, loss of exclusivity for Crestor, and the cont nued impact of early generic entry in certain markets for Faslodex, which we expect to continue in 2019. The continued macroeconomic environment, pricing pressure from payers and parallel trade across markets also affected sales. Our sales in Australia and New Zealand declined by 16% at actual rate of exchange (14% at CER) in 2018.This was primar ly due to the continued erosion of Nexium and Seroque/ by generic medicines, further price reduct ons on established brands and entry of an analogue for Symbicort in Australia, which had an impact onboth price and volume. Consequently, sales in 2018 declined at a greater rate compared to that seen in 2017.However, the pace of generic erosion has moderated notably with Crestor and Atacand, while the sales growth from new products such as Brilinta, Lynparza and the Diabetes portfolio has continued. Brilinta, Lynparza and the Diabetes portfolio grew by 4% at actualrate of exchange (6% at CER), 41% at actual rate of exchange (43% at CER) and 4% at actual rate of exchange (6% at CER),respectively. Despite these condit ons, we continued to launch innovative medicines across Europe and saw encouraging performance for certain products across our Growth Platforms, in particular with Forxiga, Brilinta, Fasenra, Lynparza and Tagrisso. Oncology sales in Europe grew by 19% {14% at CER},partly driven by the approval of Tagrisso for the treatment of patients in the 1st line EGFRm setting in June 2018. Lynparza sales grew by 46% {41% at CER), partly benefiting from the approval in May 2018 for its use as a tablet­ based treatment for platinum-sensiti ve ovarian cancer,regardless of BRCA status.Brilique sales growth of 18% (13% at CER) was accompanied by Forxiga sales growth of 30% (24% at CER).Fasenra was successfully launched in several European countries, with a strong initial uptake. Though widespread adoption of a broad national price control scheme in the near future is unlikely,we continue to comply with new state-levelregulations in this area and we recognise the sustained potential for substantial changes to laws andregulations regarding drug pricing that could have a significant impact on the pharmaceutical industry. EstablishedROW comprises Australia and New Zealand. Canada and Japan. 31 AstraZeneca Annual Report & Fonn 20-F Information 2018/ Business Revtew

 

Business Review Return to Growth continued Emerging Markets Emerging Markets, as defined in Market definitions on page 239, comprise various countries with dynamic, growing economies. As outlined in Marketplace from page 11, these countries represent a major growth opportunity for the pharmaceutical industry due to high unmet medical need and sound economic fundamentals. Emerging Markets are not immune, however, to economic downturn. Market volatility is higher than in Established Markets, and various political and economic challenges exist. These include regulatory and government interventions. In selected markets, governments are encouraging local manufacturing by offering more favourable pricing legislation and pricing is increasingly controlled by governments with price referencing regulations. for both brands in 2019. This evaluation is being applied retrospectively, so several existing generic products may fail and be withdrawn which could lead to a consolidationin the sector. This would leave fewer,higher-quality generics in the market thereby putting pressure on any originator brand price premiums and driving a reduction in overall medical costs. ll% increase in Product Sales in the US in 2018 (ll% at CER) to $6,876 million The Industry-wide growth rate is expecte e a moderate single digit percentage following the u dates of the NRDL and (iXOinding health insurance coverag . Nevertheless,the healthcare environment in China remains dynamic.Opportuntiies are arising from incrementalhealthcare investment, strong under1ying demand for our more established medicines and the emergence of innovative medicines such as Tagrisso and Lynparza. 28% increase in Product Sales in China in 2018 (25%at CER) to $3,795 million "AstraZeneca was the fastest-growing top 10 multinational phannaceutical company in Emerging Markets in 2018." Growth drivers for Emerging Markets include new medicines across our Oncology,CVRM and Respiratory portfolios. To educate physicians about our broad portfolio, we are selectively investing in sales capabilities where opportunities from unmet medical need exist. We are also expanding our reach through multi-channel marketing and external partnerships. DJ For more inform3tion on our work inChina, $ee page 37. Emerging market healthcare We continue to make our medicines affordable to more people on a commercially and socially sustainable basi s. As,on average, almost half of medicine funding in emerging countries is paid for by the patient or their families, we base our approach in these markets on an understanding of their economic circumstances and the burden placed on them by health costs. We are aiming to enable our Emerging Markets to deliver better and broader patient access through innovative and targeted equitable pricing strategies and practices. With revenues of $6,891 million, straZeneca was the fourth largest multinationao:..-.-­ harmaceutical compai')Y, as measure ("prescription sales, and the fastest-growing) p 10 mult nationalpharmaceuticalcom an 1n Emerging Markets in 2018 China In China, AstraZeneca is the second largest h rmaceut cal company by valu in h (hospital sectora. s measured,by saieS)Sales in China in 2018 increased by 28% at actual rate of exchange (25% at CER) to $3,795 We have a variety of access programmes around the world,each tailored to meet the needs of the localcommunity,which include a patient's ability to pay.These include patient assistance programmes.such as Terapia Plus in Ukraine,Karta Zdorovia in Russia and FazBemin Brazil. Through these programmes, we help qualifying patients with discounts and donations. We provide these programmes in markets wtih limited or no public reimbursement system, no coverage beyond the most basic therapies,or where it is unlikely or only after an extended period that public reimbursement is a possible consideration. million (2017: $2,955 million). e delivere sales growth above the growth rate of the m ital market sectOQthrough strategic brand investment, systematic organisat onal capability improvements and long-term channel expansion programmes in our main therapy areas. In addition, Tagrisso was listed in the Nat onal Reimbursed Drug List (NRDL) and we launched Lynparza during 2018. Pricing practices remain a priority for regulators, and new national regulations, in addition to provincialand hosptial tenders, continue to put increasing pricing pressures on pharmaceutical companies in China. In addition, the planned roll-out of the Generics Quality Consistency Evaluation (GQCE) will have an impact on pharmaceuticals budgets and pricing through setting new standards for bioequivalence that generic products must adhere to.The outcome of the latest round of tenders involving Crestor and lressa were announced in December 2018 with implementation from early 2019. This is expected to result in a level of sales decline AstraZeneca also aims to partner with countries' healthcare systems to optimise access to healthcare.For example.in South Africa, Phakamisa supports the heahhcare system by bringing together different organisations to strengthen healthcarecapabilities andimprove access to treatment and support networks. It aims to reduce the burden of breast and prostate cancer through the promotion of primary prevention and early detection. AstraZeneca AnnualReport & Form 20-F fnformation 2018/ Strategic Report 32

 

Unmet medical need and world market > Cancer is the second leading cause of death globally. > Lung cancer has the highest cancer mortality rate, responsible for the deaths of 1.7 million people worldwide in 2018, followed by colorectal, stomach, liver and breast cancer. > Breast cancer is among the most common types of cancer, affecting 4.6 million people worldwide. Other common cancers include prostate and ovarian cancer. Estimated annual cancer cases (m) ''Z04o· ································ 29.5 2030 2018 22 18 l.7m Lung cancer was responsible for the deaths of 1.7 million people in 2018. 70°/o Approximateyl 70% of the world's cancer deaths occur in low-and middle-income countries. Tlieral!y area world marKet (MAT/Q3/18) $106.6bn Annual worldwide marJ('e"t' v-a.lu-e' I £bsmgt2.Sbn I Honnooal thempios $12.5bn I Monodonal antibocbes (mAbs) $27.3bn $3:0:il@ I Small mole I ·-Cl<M<oncology the!ap>e.s SO.Ibn Source-: JQVlA &tra:Untea focuseu on peclfic t eom nt.o;, within this overall therapy are.:markel 50 AstraZeneca Annual Report & Ponn 20·F tnformatton 2018I Strategic Report

 

 

Unmet medical need and world market 20m Number of deaths from CVRM diseases worldwide every year. >93°/o Proportion of people with type-2 diabetes that have at least one other CV, renal or metabolic condition. $183.8bn Annual worldwide market value I · I CKDr;&iW#d er eem m $2. $0.3bn 0. r C:V $3B.abn Source-:JQVlA &tra:Untea focuseu on peclfic t eom nt.o;, within this overall therapy are.:markel CVRM total sal stXthtdet. parUoJ.ldouble counting o1 hyperkalaemlaand CKOassociated .tuaem.!.a markru.alt-s, wlu<:h rt1iultt>!Jow deti.mhons overlapping wlth CKO andotherCV AstraZeneca Annual Report & Ponn 20·F tnformatton 2018I Strategic Report 56

 

Unmet medical need and world market Today, more than 700 million people have asthma or chronic obstructive pulmonary disease (COPD). About 250 million of these people are in our 12 largest commercial markets, but more than 175 million of these individuals do not receive maintenance treatment for these chronic diseases.Despite currently available medicines, therapeutic advances are needed to reduce morbidity and mortality. 339m Some 339 million individuals worldwide haveasthma, with prevalence expected to rise. Severe asthma accounts for about 10% of asthma patients but 50% of the physical and socio·economic burden of asthma. Millions of patients underuse their anti-inflammatory maintenance controller treatments (which treat the underlying inflammation of thedisease) and are reliant on reliever medications. We estimate that new medicines and Emerging Markets will drive 7% annual growth over the next decade, reaching $47 billion by2028. 384m Globally, some 384 million people have COPD, and it is predicted to be the third leading causeof death by 2020. COPD exacerbations represent a significant burden for patients, carers and society. Even one severe exacerbation can significantly reduce lung function and is associated with higher mortality. Therapy are jMAT/QJ/18) orld market $68.4bn Annual worldwide market value IIAl!ihiT>iS20.Sbn' I l6.2bn OUlt'r$31.7bn Sot1rce:IQV!A. Al>lraZto.n«-a focuseon spcc fic seom<'ntli withm this o\•erall tl1erapyarea market. 62 AstraZeneca Annual Report & Ponn 20·F tnformatton 2018I Strategic Report

 

I 2• "'' ", g• Our strategy for Respiratory Respiratory is one of our main therapy areas, and our medicines reached more than 18 million patients as maintenance therapy in 2018.We have a strong pipeline with more than 33,000 patients participating in Phase I-IV respiratory clinical trials across the world. Our ambition is to transform outcomes for patients with respiratory diseases through: mber 20 JZ.Easenra alrea y lea the IL-5 classinnew rescri tions"'"n'""th''"' S and Ran In the future, tezepelumab, a potential first-in-class anti-thymic stromal lymphopoietin (TSLP) mAb that blocks a key upstream driver of inflammationin asthma, has the potential to become "the broadest biologic for the treatment of persistent uncontrolled asthma seen to date"' if the Phase Ill programme ref ects the positive Phase lib data, as noted in the New England Journal of Medicine. 1. Our strength in inhaled combination medicines. 2.A leading biologics portfolio. 3.A robust early pipeline where our goal is to achieve disease modification, early intervention and cure. In inhaled medicine, our focusis on two key areas of clinical care.In asthma, we are working to prevent attacks by reducing over-reliance on reliever monotherapy and advancing anti-inflammatory reliever therapy, whichis now under regulatory review for a licence extension based on the landmark Symbicort Turbuhaler SYGMA trials.We continue to invest inSymbicort given its value in the treatment of asthma and COPD, also reflected by its continued leadership in the ICS/ LABA class.In COPD.we are advancing our next generation inhaledAerosphere portfolio with the ambition of reducing exacerbation rates using our invest gational triple therapy, PT010,earlier in the course of the disease than recommended in guidelines today. Our early pipeline continues to grow and includes new drug modalities allowing us to address hard-to-reach targetsin the lung that were previously seen as inaccessible, for example: the Anticalin protein AZD1402, an inhaled IL4Raantagonist currently in Phase I development for asthma,in collaboration with Pieris Pharmaceuticals. Our respiratory market leadership in China positions us well to support improvements in acute treatment using our leading nebulisation portfolio and establishing maintenance inhaled treatment as the standard of care in asthma and COPD. Each day the paediatric nebulisation programme we support treats 300,000 patients, enabling them to receive guideline-recommended acute care for their condit on. In biologics,we aim to transform outcomes among pat ents with the greatest unmet medical need and relegate chronic oral steroid use to last resort, given its association with adverse events. Our first respiratory biologic,Fasenra, is for severe eosinophilic asthma and is being investigated for other eosinophil-driven diseases.lpproved · ElisabethH. Bel.Moving Upstream-Anti·TSLP in Pennstent UncontroiJed AsthmJ. New England Jot mal ofMedtcine. 2017: 377:10. AstraZeneca Annual Report & Form 20-F Information 2018 / Therapy Area Revtew 63

 

• ;• • '• help patients with severe asthma Eosinophils,a t ype of white blood cell,are a normal part of the body's immune system, but for some people with severe asthma, they can make inflammation in the airways worse. Fasenra is the only biologic to directly target the 1L-5a receptor and deplete eosinophils by recruiting natural killer cells. Early clinical trialsshow Fasenra depletes blood eosinophils within 24 hours after a single dose. granted Orphan Drug designation by the FDA for the treatment of eosinophilic granulomatosis with polyangiitis and more recently, hypereosinophilic syndrome. Since its approval in November 2017, more than 21,000 asthma patients have received Fasenra, whic now leads the IL 5 class innew prescriptions in the US and Japan. A feature of Fasenra•s launch has been the anecdotal stories clinicians have shared with us about the positive difference it is having on their patients' lives. Severe asthma is a debilitating disease, which impacts many aspects of a patient's life and these stories reflect the difference an effective biologic medicine can have for these patients. Fasenra isnow approved and launched in 35 markets as an add·on maintenance treatment for patients with severe, eosinophilic asthma. Patients receive Fasenra as a fixed·dose subcutaneous injection via a pre-filled syringe every eight weeks after initial loading doses. Fasenra has been investigated for self-administration and in an autoinjector device; regulatory submissions were made in 2018 and we anticipate decisions in 2019. In addition, Fasenra is being investigated for indications in other eosinophil·driven diseases. including severe nasal polyposis, and has been 2018 review -strategy in action Strength in inhaled combination medicines Our strength ininhaled combination medicines was reflected in 2018 with Symbicort, whoch retainedits gosotion as the number one ICS/ LABA combination lo9a!!till..volume terms and is a cornerstone of current asthma and COPD care. We continue to invest in Symbicort, which remains AstraZeneca's number one medicine inProduct Sales in 2018. The launch success of Fasenra also supports our view that biologic treatment rates will significantly increase in the coming years in line with the evolution of treatment in other inflammatory diseases. Pricing pressure contonues to impact Symbicort performance but was in line w h expectations as prices rebase ahead of anticipated generic entries. This trend continues to be offset by Emerging Market growth.led by demand for acute and maintenance care in China.In March, the NMPA approved Symbicort Turbuhaler as a maintenance and reilever therapy, designed for the treatment of asthma in adolescent patients (12·17 years) in China. controller treatments,resulting in preventable exacerbations.In China, the Chinese Journal of General Practitioners guidelines were updated to incorporate the SYGMA data. This update recommendedSymbicort as a potentialtreatment for all asthma seventies. During the first half of 2018, the Phase Ill SOPHOS trial read out, which compared two doses of PT009 to PTOOS.PT009 met its primary endpoint and delivered superior efficacy to PTOOS at morning pre-dose through forced expiratory volume (FEV) 1 at Week 24.In September 2018, the TELOS Phase Ill trial, which investigated the efficacy and safety of PT009 in patients with moderate to very severe COPD,regardless of whether or not they had had an exacerbation in the prior year, showed that PT009 is an eff ective maintenance treatment for patients with COPD and a suitable comparator for PT010. The data were presented at the European Respiratory Society Congress and were published in the European Respiratory Journal.SOPHOS and TELOS were designed to quailfy PT009 as an active comparatorin the PT010 clinicaltrial programme. We significantly progressed all Phase Ill trials supporting PT010-KRONOS, SOPHOS, TELOS and ETHOS. The Phase Ill KRONOS trialwas published in September in The Lancet Respiratory Medicine.KRONOS evaluated the efficacy and safety of triple combination therapy, PT010, versus dual combination therapies Bevespi Aerosphere, Symbicort Turbuhaler and PT009.In the trial, PT010 met six of seven primary endpoints versus dual comparators and PToog met two non-inferiority endpoints to support the qualification of PT009 as an active comparator. In a key secondary endpoint, PT010 showed a statistically significant 52% reduction in the rate of moderate or severe COPD exacerbations compared with Bevespi Aerosphere In a patient population that was not required to have had an exacerbation in the previous 12 months.The adverse events profile was consistent with that observed in previous trials and the incidence of adjudicated pneumonia was low and comparable in all treatment arms. In May 2018, positive results from the Phase Ill SYGMA trials of Symbicort Turbuhaler were published in the New England Jovmal of Medicine and presented at the American Thoracic Socoety International Congress. The trials,which met their primary objectives, evaluated the efficacy of Symbicort Tvrbuhaler, taken only as needed without maintenance therapy, as an anti-inflammatory reilever compared with standard of care medicines for mild asthma.In November, we announced that the Swedish Medical Products Agency had accepted our regulatory submission for the EU to expand the indication for Symbicort Turbuhaler, as ananto·inflammatory reliever as needed,in patients with mild asthma.Millions of patients with asthma are reliant on their reliever medications. which improve symptoms but do not treat the inflammation of this disease. and they underuse ant -inflammatory maintenance In July 2018, the ETHOS Phase Ill trial,which further investigates the efficacy and safety of PT010, completed enrolment of 8,400 paltents across 28 countries. In addition,during the second half of 2018, the regulatory submissions for PT010 were accepted by the Japan MHLW and the China NMPA, based on the KRONOS Phase Ill trial. In January 2019,PT010 receoved Priority Review designation from China's NMPA. AstraZeneca AnnualReport& Form 20-f' Information 2018 / Therapy Area Review 65 Science

 

I 2• "'' ", g• Synagis has become the global standard of care for RSV prevention and helps protect at risk babies against RSV.Synagis is approved in more than 80 countries and we continue to work with our worldwide partner,AbbVie, outside the US, to protect vulnerable infants. We are progressing MEDI7352 in painful diabetic neuropathy, which is in Phase II and continue our collaboration with Takeda on MEDI1341for Parkinson's disease, which is in Phase I. Gastrointestni al se of Nexwm continued to grow 1n a lim1te umber of markets such as China and a i 2018.This growth is expected to continue following additional approvals in China for high-dose treatment of peptic ulcer bleeding and in Japan for paediatric patients from the age of one, with the innovative Nexium sachet formulation. The re-examination periods for adult indications/dosage of Nexium capsules and Nexium sachets have been extended for two years in Japan,until 30 June 2021. This enables the completion of another clinical trial for long-term treatment in the new paediatric population. Nexium is subject to generic competition globally, except for Japan. In May 2018, we announced an agreement with Luye Pharma for the sale and licence of the rights in the UK, China and other international markets to Seroque/ and Seroque/ XR. We had previously partnered the rights to Seroquel and Seroque/ XR in Japan and Venezuela under prior agreements. Seroquel, used primarily to treat schizophrenia and bipolar disease,has lost its compound patent protection globally. The Seroque/ XR formulation patents have now also expired in the majority of markets. In November 2018,we announced the divestment of Synagis' US rights lo Sobi. Sobi will commercialise Synagis in the US and around 130 AstraZeneca employees will transfer to Sobi as part of the transaction. Sobi also has the right to participate in payments from the US profits and losses for MEDI8897. MEDI8897, an extended half-life RSV mAb being investigated for the prevention of LRTI caused by RSV in infants and young children, is progressing in collaboration with Sanofi. It is being developed for use among a broad population of late pre-term and healthy full-term infants, so that they may only require one dose during an RSV season. In November 2018,we announced that the primary analysis for the pivotal, Phase lib trialto evaluate the safety and efficacy of MEDI8897 showed that the trialmet its primary endpoint. Following these results, in January 201g, the EMA granted MEDI8897 access to its PRIME (PRiority MEdicines) scheme and in February 2019,the FDA granted Breakthrough Therapy designation for MEDI8897. In October 2018, we announcedIhat we had entered into an agreement with Grunenthal for the rights to Nexium in Europe and Vimovo worldwide (excluding the US). Autoimmunity and inflammation In February 2018, six molecules from our early-stage inflammation and autoimmunity programmes were spun out into an independent biotech company,Viela Bio. The new company will focus on developing medicines for severe autoimmune diseases by targeting the underlying causes of each disease.The molecules include inebilizumab, currently in Phase II trial development for the treatment of neuromyelitis optica spectrum disorder, a rare condition that affects the optic nerve and spinal cord in approximately five in 100,000 people. In January 2019,Ironwood announced they had received marketing authorisation from the NMPA in China for Linzess for the treatment of patients with irritable bowel syndrome with constipation. We entered into a collaboration in China with Ironwood in 2012. Neuroscience In June 2018,we announced with Lilly, the discontinuation of the Phase Ill clinicaltrials of lanabecestat, an oral beta secretase cleaving enzyme (BACE) inhibitor, for the treatment of Alzheimer's disease.The decision was based on recommendations by anindependent data monitoring committee,which concluded that both the AMARANTH trial,in early Alzheimer's disease, and the DAYBREAK-ALZ tria,l in mild Alzheimer's disease dementia,were not likely to meet their primary endpoints upon completion and therefore should be stopped for futility. As a result of this decision, the related AMARANTH extension trial was also discontinued.High-levelresults in December 2018 of the AMARANTH and DAYBREAK-ALZ trials confirmed no significant disease slowing was observed in any of the Phase Ill trials, confirming that the action to discontinue the trials was the correct decision. We announced in August 2018 that anifrolumab, a developmental mAb that inhibits the activity of all type Iinterferons (IFN), did not meet the primary endpoint in the TULIP 1 Phase Ill trialin systemic lupus erythematosus (SLE).A full evaluation of the combined TULIP 1 and TULIP 2 data will be conducted to determine next steps for anifrolumab in SLE. The Phase II trials in lupus nephritis and for a subcutaneous route of administration in SLE remain ongoing, as does the long-term extension trial in SLE. Our product$ While this Therapy Area Review concentrates on our key marketedproducts., tntmY of ourother product$ are erucial to our bu.sine.ss in certain countries in Emerging Markets. In April2016, AstraZeneca licensed its US rights to develop and commercialise Zurampic and Duzallo to Ironwood. In August 2018, Ironwood notified AstraZeneca of its intent to terminate the licence for convenience. In November 2018, Ironwood notified the FDA that it had discontinued the manufacturing of the products and contemporaneously informed AstraZeneca that it is working on withdrawing the NDAs for these products and terminating the FDA required post-marketing study.This process is expected to take several months. [0 Formore informationon our potenhal new productsand product life..cycle developments, pleutthe Therapy Area pipehne tables on pages 52,58, 64 and 68 and the Development Pipeline table rrom Pf.Qe 212. forinform-.tion on Patent Bxpines of our Key Marketed Products, see from page 217. lndlcations for each productdescribed in thisTherapy Area Reviewmay vary among countries. Please t ee local prescnbmg informahon foroountry· specific indications for any particular product. Forthose of our products subject to litigation.information about material legal proceedings can be found in Note 29 to the Financial Statements from page 194. Details of relevant risks are set out in Risk flom page 220. We also collaborate with Lilly on MEDI1814, an antibody selective for amyloid-beta 1-42 (A 1-42) that is currently in Phase I trials as a potential disease-modifying treatment for Alzheimer's disease. AstraZeneca Annual Report & Form 20-F Information 2018/Therapy Area Revtew 69

 

I 2• "'' ", g• Growth Platforms In the periods under review, our Growth Platformsincluded products in our three main therapy areas,and a focus on the Emerging Markets and Japan.Our Growth Platforms grew by 13% (CER: 12%), representing 84% of Total Revenue after removing the effect of certain Product Sales which are included in more than one Growth Platform. Externalsation Revenue Details of our significant business development transactions which give rise to Externalisation Revenue are given below: monotherapies or combination therapies will be shared equally.MSD will fund all development and commercialisation costs of Keytruda in combination with Lynparza or selumetinib.AstraZeneca will fund all development and commercialisation costs of lmfinzi in combination with Lynparza or selumetinib.AstraZeneca will continue to manufacture Lynparza and selumetinib. As part of the agreement,MSD will pay AstraZeneca up to $8.5 billion in total consideration, including $1.6 billion upfront, $750 million for certain licence options and up to $6.2 billion contingent upon successful achievement of future regulatory and sales milestones. Of the upfront payment of $1.6 billion,$1.0 billion was recognised as Externalisation Revenue on deal completion in 2017,with the remaining $0.6 billion deferred to the balance sheet. AstraZeneca will book all Product Sales of Lynparza and selumetinib; gross profits due to MSD under the collaboration will be recorded under Cost of Sales. > In November 2017, MSD exercised the first licence option resulting in Externalisation Revenue of $250 million. > In January 2018. the FDA expanded the approved use of Lynparza to include the treatment of patients with certain types of breast cancer.The approvaltriggered a $70 million milestone payment from MSD to AstraZeneca. > In June 2018, net sales of Lynparza reached $250 million cumulative sales threshold, triggering a sales-related milestone of $100 million to fall due to AstraZeneca. > In November 2018, MSD exercised the second licence option resulting in Externalisation Revenue of $400 million. In addition to the exercise of this option, net sales of Lynparza reached the $500 million cumulative sales threshold, triggering a sales-related milestone of $150 million to falldue to AstraZeneca. > In December 2018, AstraZeneca was notified of an FDA approvalof Lynparza,which triggered the SOL0-1$70 millionmilestone payment to AstraZeneca. > In March 2017, AstraZeneca announced an agreement to develop and commercialise MEDI8897 jointly with Sanofi. Under the terms of the globalagreement, Sanofi made an upfront payment of €120 million and will pay up to €495 million upon achievement of certain development and sales-related milestones. All costs and profrts are shared equally.The US element of this collaboration is the subject of a participation agreement with Sobi, entered into in November 2018 and effective 23 January 2019. > In November 2018,AstraZeneca entered into an agreement with Swedish Orphan Biovitrum AB (Sobi) to sell the US rights to Synagis. Under the agreement Sobiwill also have the right to participate in AstraZeneca's share of US profits and losses related to MEDI8897.The deal was completed on 23 January 2019 and AstraZeneca received an upfront consideration of $1.6 billion, including cash of $966 million and ordinary shares in Sobiwith aninitial market value of $600 million.This income was recorded in 2019. AstraZeneca will also receive up to $470 million in sales-related payments for Synagis, $175 million following the submission of the Biologics License Application (BLA) for MEDI8897,potential net payments of $110 million for other MEDI8897 profit-related milestones and $60 million innon-contingent payments for MED18897 during the period from 2019 to 2021. > In December 2017,AstraZeneca entered into an agreement effective January 2018 with Almirall, under which Almirall is granted an exclusive and perpetual licence to distribute and undertake certain manufacturing activities related to Crestor and Provisacor in Spain. Almira!! made an upfront payment of €51 million on completion of the deal and will pay additionalsales-related milestones of up to €55 million plus a royalty for ten years. > In July 2017,the Group announced a global strategic oncology collaboration with MSD to co-develop and co-commercialise AstraZeneca's Lynparza for multiple cancer types.Under the collaboration, the companies will develop and commercialise Lynparza jointly, both as monotherapy andin combination with other potentialmedicines. AstraZeneca and MSD will also jointly develop and commercialise AstraZeneca's selumetinib, an oral. potent, selective inhibitor of MEK,part of the mitogen­ activatedprotein kinase (MAPK) pathway, currently being developed for multiple indicationsincluding thyroid cancer. Independently, AstraZeneca and MSD will develop and commercialise Lynparza in combination with their respective PD-L1 and PD-1 medicines, lmfinzi and Keytruda. Under the terms of the agreement, the two companies will share the development and commercialisation costs for Lynparza and selumetinib monotherapy and non-PD-L1/ PD-1combination therapy opportunities. Gross profits from Lynparza and selumetinib Product Sales generated through Product Sales in Emerging Markets grew by 12% compared to 2017 (CER: 13%) to $6,891 million partly driven by a strong performance from Tagrisso with growth of 157% (CER: 159%). Product Sales in China increased by 28%in 2018 (CER: 25%), representing 55% of Emerging Markets Product Sales in the year. Product Sales of Respiratory medicines increasedby 4% (CER:3%),with the impact of pricing pressure in the US for Symbicort being more than offset by a strong performance by Respiratory in Emerging Markets and higher demand for Pulmicort in China. New CVRM grew by 12% (CER:12%) with revenue of $4,004 million (2017: $3,567 million). Within New CVRM, sales of Brilinta in the year were $1,321 million,an increase of 22% (CER: 21%). rilinta salhwere up 16% to $588 million, as it emained th lillii!j"Qed oral anti-platelet market leaae;l Our Diabetes Product Sales were 8% higher than in 2017,driven primarily by growth of 30% on Farxiga (CER: 30%) with globalsales of $1,391 million as it continued to be our largest-selling Diabetes medicine and SGLT-2 class growth was supported by growing evidence around cardiovascular benefits, including data from the CVD-REAL study that was published in March 2017. Japan Product Sales declined by 9% (CER: 11%) with growth on Tagrisso and Forxiga, outweighed by the impact of the entry of generic competition to Crestor in 2017. Product Sales of Oncology medicines increased to $6,028 million in 2018 (2017: $4,024 million), $1,860 million of which came from Tagrisso (2017: $955 million), which continues to be our leading medicine for the treatment of lung cancer and received regulatory approval in more than 55 countries by the end of 2018. AstraZeneca Annual Report & Form 20·F Information 2018/ Financial Revtew 79

 

RuudDobber Executive Vk·•P'ruldent, BioPharmac:euticals Business Ruod was appOinted £xecubW v David Fredrickson Exteutive Vice·President. OncoloQy Business Dave was appooted i:x&Cutwe Vit4!1:•Presidenl, GlobalHeadOncology Busi"'ess nOctober 2017 and 1S responsible fet dt1w•g growthand maxim1snglMcommercialper'ormance ol thegtobatoncologyandhaernatology portfobo.Inaddlbon.he plays a critical l adat&hiP tole in satmg tM Oncology portfoltoandproduct strategy fOf' the org3fllsatJOn.PteVlously.Dave servedas P1esk16tlt of A:.lutZeneca K.K.11'1 Japan.and Vice-President.Speciatfy Care1nthe US, spann•ngoncology, lnfecl;ous d1sease. andneuroscience. m&dJCines.Oaw join d Al'ltraZeMca ftom Roclle/Gena'ltec-...h in 2014,where he was 8U$.1lleSS Vnl1Manager. OncOlogyr1Spain.and htJki gfowilg commerc'-'31responsibilities ;nstrategy, marketingandsales10 the US.Me also served tornino yGdl'& at U1eMOI\riDr GrQup,LLC {now Monrtor OeJoitte Group.LLC).a globalstrategy consuttancy. Hehas' ervedas Vlee ChaJfman of theEur anF-cterat.on ot Pharmaceutical Industries arv.:l Associations (EFPIA).Japan and was amember of theBo3f<f of theJapar PharmaceuticalManulacturors ASS<:Ic.a:Uon {JPMA).He is a graduate of C:Jf'lorgl!town UoMm;ny (DC) •nGo\o-etnment. Menelas Pangalos Executive Vice·Prtsident.Re$Utch & Development BioPbarmaceuticals ManaPangaloswas appor.tedasExecutive Vice-PresidentR. &D S.OPharmaceutcals in Ja,...,ary 2019 andIs responstlle for R&D from diS.CO\Iary through toJatewst.agedewbpme:nl for CVRM andRespiratQfy.Pnorto th1sh, e served asExecu1,\•e VICe-Presidentof AstraZ neca·s IMED BiotechUnit and Gk>baiBusiness Development.S1nce j0l'11ng AstraZeneca in2010 Mene hasled a translorrt.atiOnof ourA&O prOductivity andhl!l c:l"amp1onedanopen appro.1ch to working Vlith aca::lemlc anct otherextemaJl )&'tnets,Mene pfl:J\'IOU Iy heldseniOI'FI&.O roles at Pflzar, 11\f •ethandG--SK.Mene hok:ls.mHonOfary PI"D fromGlasgow lkll-..etSityandIs aFellow olthe Academy 01MedicalSciooces,theRoyal Socie yof Btologyand Clare Hall, \Jr1i\ rsity of C3/T'Ibt.OgeH. e sits oo theMedteat Research Council,co chalrs theUfe Soiu!'lces Couoc• Expert Group on lnnovabon,Cbr.calRese.vch anciData andIS amemberof the Life Sciences IndustrialSttategy1mpiiJmanldtJOn Board andNatiooalG!!lnomics Board.He1s alsoa 6cJIOmember ot the BntiSO PhatlllaCeuncal GfoupandCarnbt'JIJgtJUnrverscty'sJud!)e Bmnne-ssSchool Jeff Pott Gener31 Counsel Jeff was app01r1tecJ GeneralCounselInJanuary 2009 andhas o...wallresponsibi!lty tor all aspectsof A.c;traZeneca's Legala.dIP func:tJon. He JOined Astraleneca In t995and has worked nvarious litigatiOn r s.Vltlere hehas had responsibliity for IP,ant:Hrus.t andprodl..;et llabllo1)' lrttgatoo.Before,o!nng AWaZeneca. he:;pent fc\ltl years at theUS legaJ htrn Omker Sidcle and Reath UP.where he specialised1n phannaceu11cat product liability lltlgatloo and anti..UUsal dvice and lllig.at.on.H& teCENYed h b.'lchelor's degee inpolr.•cal science from \Ahleatoo College andhis Jur.s OoctOt Degree frol'l'l VlanO\ItlUnlv&rsity Sct\oool llaw. I Presldant. BicPharmac:e-Jticals Business in January 2019 Met Is respons.-oforproructstra1egy af\d cornrnen:1al&111/ef'tor CVRM andFtaspiratory. Prior to Ihis,Ruudheld theroleofExecutive VIce-President,NonhAmerica andvi3.S nsib l IOf drrvnggrowthand!T".axtmi$ing the contribu ion of the CQmmei"C\31Cf!E!ra110ns InNOfth A"ner-ca.Rvud joined Zeoecan1997 andMs held va11ous seniOr cornmerctaland leader htproles includingExecutive VIce-President.EuropeR. wd was also l'lsibla for lha davalopmentolour late-stage,smallmoleculeontibiotlc ppeine as wellasIts globalCOf'Mierc!<lliSatlcnand was RaglortalVlce-Pr1:1Sident few-l::.uropean.Middla East andAfncanregton, RegJonillVce­ Prestdeot #or the Asia PaCJfic region and tmenm E:xee<JtlvaVica..Prestc9'1t. GPPS.Awd wa a memberof the BoardandExeo..rttYB C'A!mmltieE" of theEuropeanFede.raticn ofPharmaceutical IndustriasandA.ssoci;)tlons and was 'f'tJVioudy Ch.3irman of the Asa civision of Pharmaceutical Research andManufacturers of Amenca.Ruvd holds a dOCIOratQ In trmut'otogylro•n lha Un'fl/efsrty otLeiden.Ne:herlands and began Illscareeras arese31'Cfl scientist In il'ntounologyandageing. Appointed p<>st ye.ar end Leon Wang Extcut ve Vice Pre$iden , International and China Pres dent Leon Wang :s Executcve Vcce·PrGMfGnt. Internationaland Ch naPresidem.He is responsible for the overallstrategy and1or dr1VW'IQ sustatnaele growth acro$S the r&gtOf"l. Leon jmned AsttaZeneca China in March 2013 and waspromoted oo Presu ert of AstraZen&ca Chif\a .n 2014.Under Leon's Jose Baselga Exe¢·utive Viot·Pre$ident, Research & Development Oncology Jos6 JOined Astral$neca 11"1JarliJary2019 as. ExectJtive Vic&-?resicen;.R&D Oocobgy and ISrespons1ble fOt theoncotogyportfollo from d!scOVtl'y lhrou<,Jh to ta:e·staga development. Ha was fotmerty Physician-in-Chief a!Mel'fl<:lfl.'!.l SIOO.'lKettertngCafi.CerCe"lter,whichbecame tne f&ad!MIneatly-phasecl!nclaJ trials ror cancer therapies and diagnostic genetic sec;venc1nf1under his leaQership.In addrtlon, hG wasProlessor 01MediCine.at W&UIComelt MedicalCollege andPre:so::lerrt of1he American ,.\ssoccahon forCancer esearctl"'AC. Jose JS anll'lternabonalUlought loaduronit•ncv.·allcn in \..ancercare ar.dctnicalresearch.Hiswork has Sed to the approvalof llfe-sav109tancer tnorapies and the etoatwn of Stl\<Gral b«>pharmaceut1calcompanies.Joseis an electedmember of ttleNa110nat Academy ot MUd1C1ne.tt'IO AmtHicanSociely Of Cllnlool Investigaton.the Assoeiaoonof Amencan F'tlyslc,ans.andanefec1edFelow of tne AACFI Academy.He iS aPt!St P10Sident ot the EuropeanSociety foe MedicalOncoklgv and recentlyreceivedlhelrLifeume A<:h-evement Award.He serveon the BoardCWcctors of the American SocietyoiClinicalOnc:ok>gy andAACR. IskraReic Executive Vic<t Pruiden1,Eu ro.pt ls.qa wappolniedEx twe Vic esiOem. Europe1nApril2011and tSrespon$1ble for our BioPharrnaceoticaJ salss,mart<.etin.g and commerctalope.-at1cns acrosso...-businesses !n30 8Jrn oountrl8$l.skra lra1necJ as a Doctor o;dentalsurgery at theMedical Urwerslty cf Zagreb,Croatta.SheJOined AstraZenbca tn 2001 andhas helda va tyo4 ii'Hllarket,regionalsatesandmarketingand generalf'l".anagement roles •ncl.tdng•nEurope as1-!et:td01Com rclatOperabonsfor Croatia a,d Headof Specially <'..are CentraJ& Eastern EuropeMOMddleEas1&Afnca.ln2012,she jolntKI Asts!l:Zcneca Auss!aa$Marketing& Stratagy Oi'ectmS. he was appontedGeneral Managef'Rvssta in 2014 and,unaer her fe.aaership, siTalanoca ·uevod a leadng share tn it& three man theracv.veas and ecame a top-s()(pescn ti ExecuHve VK:e-President. AsiaPacific Reg•on.Pnor to!Oln•ng AslraZeneca,l..eon heldpoSit.ons of I"'C,eas!ng 1tsp0nsibil ty •n market.ingand business leade>.rship at Roche, where he wa-s. a B:.rslle-s.s Ur.lt Vlce­ PrMidenL In additiOn, Leon holds several positions in localtrade assooia!:iOns and o1tler prom1nent organ1sattons •n Ch•na. Leonholds an EM9A fromChina E'uropc InternationalBusiness School,anda Bacheior of Amfrom Shanghailntema+l onaJ StudtM University. bN'a's responsibilitei s W9t'8 expanded n2016 to CO\?! bolhR o ss1a and the €1)fasla AIeaI.skra was at:POntod Area Vice Prestdentot Rtrssia and Eurasia area in 2016,whereshe dmve strong pe.-fonnance ftom a 1,500-strong1eam •n a complex anddynai'!'MC region.. tskfaI".as an International Executive MBAfrom the IE IedSchoot of Management,Slovenia. AstraZeneca Annua1 Report & Fo-rm 20-F Information 2018/ Senior Executive Team 97

 

Audit Committee Report continued Committee site visit to Shanghai and Wuxi, China In October, m mb rsof the Audit Committee visited the Group's sites in Shanghai and Wuxi, China. China is AatraZeneca's &econd-largest national market, with abaolute growth that has out-performed other multinational pharmaceutical companies for,AAMr!!J years. We have approximately 13,000 employees in China. The Committee en joyed several meetings with our local management to discuss the opportunities, challenges and ris)(S being managed by senior leaders across a range of activities including R&D, commercialisation, manu.facturing, supply and distribution. The Committee also undertook a tour of AstraZeneca's Wuxi manu1acturing plant and held an informal •questionsand answers' session with a wide group of employees based in Shanghai. The Committee met physicians and patients at a large hospital in Wuxi and visited the China Commerdal Innovation Centre (an open strategie platform designed to promote innovative healthcare practices in China) as well as Oizal Pharmaceutical, a recently formed joint venture with the Chinese SDIC Fund Management Company (an innovative biopharmaceutical enterprise}, which demonstrated how innovation and its interconnectivity with smart healthcare has the potential to transform China's healthcare industry. Phttip Broadley, who will become Chatrm.a.n of the AuditCommittee in March 20l.9. dunnn the Commht41e•:; vl.$11 toChina. Further information on the Committee's visit to China can be found above. The Committee also met informally with employees from the Finance, Investor Relations,Corporate Affairs, lA.HR and Global Business Services teams. Finally,inlight of the fact that I will formally step down from the Board at the conclusion of the Company's AGM in April 2019, the Company announced that Philip Broadley has been chosenby the Board to succeed me as Chairman of the Committee.Philip,who jo•ned the Board andCommittee in April2017,is well-attuned to the working of the Comm1ttee and, with his significant lntemational business and financialexperiencehaving served as Finance Otrector at large financial institutions, the Boardbelieves he is well placed to lead the Committee in thecoming years. During 2018,Iparticipated in the UK Competition andMarkets Authority's statutory audmarket study,wh1chhas the objective of considering whether that market is operating as well as it should.Ialso participated in the Department for Culture,Media and Sport's annualFTSE 350 Cyber Security Health Survey. Changes to the membership of the Committee ShritiVadera stepped down from theCommittee in June 2018,and I thank her for her invaluable insight and significant contribution since she joni ed the Committee in 2011.We welcomed Deborah DiSanzo as a member of the Committee in November 2018.While Deborah has only served for a short period of time, her long career working at the intersection of healthcare and technology has been shown to be of particular benefit to the Committee as it continues to increase its focus on cybersecurity, the use of 'big data' andprivacy matters. We hope that you find this information helpful in understanding the work of the Committee. Our dialogue with our shareholders and other stakeholders is valued greatly and we welcome your feedback on this Audit Committee Report. Yours sincerely, «vo\Q__ ,._ _,_-- Rudy Markham Chairman of the Audit Committee 112AstraZeneca Annual Report & Ponn 20·F tnformatton 2018/ Corporate Governance

 

Glossary Market definitions uro e (CzechRepubh !lii0gary} (Luxembourg (Serbia and Montenegro @enmar@ lfstonia7 lf1nlan(t/ @iS§ Uceland) Qre§Cl1 (ISfae!) (j§iy) CLa§1 (Siovakoa) (Siovema2 ®>.ill (Swedei1J (Switzerland) 0 (§lg§ \Netherland# Q'lorway) (fO!angl (portughl) {Romania {New Zealand) (Bosma and Herzegovina? @g@! (GermanY) (Greece) (Canada} stablished RO ({QVfA1. QV1A.Mida.:t Quanlum 03 2018 daLa1§no!.ava.ilablc o.a: AsUaZcn"fa doc:;; :wL.iu.b:itl!ht;let lQVL\aYatlelh• da1..a fa; ' he:;rcoUAii1ii) The above table is not an exhaustive list of all the countries in which AstraZeneca operates,and excludes countries with revenue in 2018 of less than $1 million. Established Markets means US EuroQe andEstablished ROW. orth America means US and Canada. @iNr Established.ROW.means Australia andNew.Zea}lifid) (Oth"if Emergmg Mi rkits means all Emerg!Q_Q Mirkits except Cfitna1 ther Africa includes Angola, Botswana EthioQia Ghana, Kenya Maurit us Mozambique Namibia, Nigeria,SwazilanTanzania U anda !La'ii}bia and Zimbab\Ni) USequivalents Terms used In this Al1nual Report US equivalent Of bnef descnptton Accruals Accrued expenses C alled-up share capital Issued share capital I Creditors Uabilities/payables Debtors Receivables and prepaid expenses Earnings Net income Employee share schemes Employee stock benefit plans Fixed asset inveslments Non-current investments Freehold Ownership wilh absolute nghts in perpetuity Loans Long-term debt Prepayments Prepaid expenses Profit Income Share premium account Addiltonal paid in capitalor paid in surplus (not distributable) Shor t-term investments Redeemable securities and short-term depostts 2.39 AstraZeneca AnnualReport & Form 20·Flnformahon 2018/ Glossary