Most countries will experience an increase in pharmaceutical spending per capita by 2018

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1 6 Most countries will experience an increase in pharmaceutical spending per capita by 218 Pharmaceutical spending per capita, 213 versus 218 1,6 1,4 Pharmaceutical Spend per Capita 1,2 1, US Japan Canada Germany France Italy Spain UK South Korea Brazil Russia Mexico Turkey China India Source: Economic Intelligence Unit, 214; IMS Market Prognosis, September 214 Growth in the U.S. market will remain strong, disproportionate to its population growth; this is driven by fewer patent expiries than in previous years, innovative product launches and rising prices. Despite high growth in pharmerging countries, there remains a large difference in pharmaceutical spending per capita versus developed markets. Only France and Spain will see a contraction of pharmaceutical spend per capita in 218, due to policies intended to control spending growth. Highest growth is anticipated in China, where per capita spending is anticipated to grow by over 7% in the next five years. As the second largest market in the world, China s spend is expected to be just 9% per capita of that in the U.S. Spending used to calculate spend per capita in US$ at actual and forecasted variable exchange rates.

2 8 Annual global spending growth will spike in and moderate through 218 Global growth, Growth $219Bn Growth $35-335Bn Absolute Growth Const US$Bn Forecast Developed Pharmerging Rest of world Source: IMS Market Prognosis, September 214 In 214, developed markets will see strong growth due to fewer patent expiries, the launch of innovative medicines and price increases. The increased contribution to growth from developed countries seen through 218 is led by the U.S. and Japan, with EU5 (Germany, France, Italy, Spain and U.K.) maintaining relatively low levels of growth. Growth in developed markets will moderate; with patent expiries and pharmaceutical costcontainment measures expected to limit prices, rising volumes will be a significant contributor to overall market growth. Largely driven by China, which represents 46% of the pharmerging market, growth in pharmerging markets will continue, driven by improved access and population increases, but will moderate in the latter years of the forecast. Developed: U.S., Japan, Germany, France, Italy, Spain, U.K., Canada, South Korea. Pharmerging: China, Brazil, Russia, India, Algeria, Argentina, Colombia, Egypt, Indonesia, Mexico, Nigeria, Pakistan, Poland, Romania, Saudi Arabia, South Africa, Thailand, Turkey, Ukraine, Venezuela, Vietnam. Absolute growth in constant US$, excludes the impact of exchange rate changes, which are expected to have approximately -$18Bn impact by 218.

3 9 Off-invoice rebates and discounts will reduce net manufacturer sales growth by approximately 25% Global market growth moderated by rebates and $29-32Bn $6-8Bn $194Bn $63Bn $22-25Bn $132Bn Sales growth Rebate and discount growth Net sales growth Source: IMS Market Prognosis, September 214: IMS Institute for Healthcare Informatics, October 214 Off-invoice discounts and rebates moderate the growth of the global market through 218 but are not reflected in IMS forecasts; the global CAGR net of discounts and rebates is estimated to be.5% lower than IMS forecast. Cost-containment policies in developed and pharmerging markets alike are increasingly driving price concessions, often through offinvoice discounts and rebates. Increases in negotiated discounts are counteracting list price increases, and populations aging into public pay systems may have a higher level of negotiated rebates. Influencing this trend are government-mandated rebates and new caps instituted on total levels of public drug spend combined with manufacturer payback arrangements in some countries. Price concessions for branded products are expected to increase through 218 and those for generics also are expected to grow as generics companies compete with increasing intensity. Estimated net spending adjustment is based on a comparison of company-reported net sales and IMS-reported sales in the U.S., and investigation and modeling of government-mandated or commercially driven supply chain discounts and rebates in other countries. IMS estimates of total spending are based on IMS audits, most often collected at invoice prices from wholesaler transactions and which do not reflect off-invoice discounts and rebates in most markets.

4 1 Global spending growth will peak in 214 at 7%, 4-7% CAGR through 218 Global spending and growth, CAGR, 4-7% 1,4 14% 1,2 12% Spending US$Bn 1, % 8% 6% 4% 2% Growth Const US$% % Sales Growth Forecast Source: IMS Market Prognosis, September 214 Global growth will peak at 7% in 214, the highest growth since 24 when it was 7.7%. Strengthening of the global economy, fewer patent expiries in developed markets, new medicines and growth in pharmerging markets will contribute to a CAGR of 4-7% through 218. Growth will peak in 214, driven predominately by the U.S. market, which is forecast to grow 11-13% in 214 and moderate to CAGR through 218. Price increases, mostly in the U.S., contributed to growth in 214, driven by some specific products and therapy areas where list price increases were above historic norms, and are expected to moderate through the rest of the forecast back to historic levels and be offset by off-invoice discounts and rebates, which are not reflected here. Chart shading indicates forecast, and forecasted growth shows point forecast and high-low ranges. Spending includes retail pharmacy, mail-order, long-term care and institutional drug spending tracked by IMS audits. Total market sales forecasts take into account the audited sales as well as any distribution channel not audited by IMS Health. The unaudited share of the market is assumed to remain constant for the duration of the forecasting period. Spending in US$ with variable exchange rates. Growth in US$ at constant exchange rates.

5 KEY COUNTRIES 18 North America continues to contribute the largest proportion to growth, but Asia is gaining Geographic distribution of medicine spending Spending Source of Growth $989Bn $1,28-1,31Bn $35-335Bn 4% 4% 6% 37% 7% 24% 29% 38% 7% 19% 36% 4% 9% 9% 36% Africa & Middle East Europe Asia/Australia Latin America North America Source: IMS Market Prognosis, September 214 Strong economic recovery in the U.S. and recent healthcare reform have already had a positive impact on the use of medicines and will grow the market through the first half of the forecast period. Drug spending in Europe will remain limited by a weak economic recovery, low population growth and continued efforts to reduce public debt, including healthcare and drug spend. Asian export economies, including South Korea and India, will grow along with global recovery, increasing demand for medicines in Asia. Southeast and East Asia will grow at twice the global average, driven by population growth, rising incomes and improved access to healthcare. Political tensions in Russia, Ukraine, Thailand and Hong Kong pose a threat to economic stability and negative price pressure from government cost-control initiatives may also limit growth. Unrest in the Middle East and North Africa will further weaken Africa and the Middle East (AFME) economies and investment, although medicine spending growth is expected to continue with rising incomes in Africa and continued immigration to the Gulf region. Spending in US$ with variable exchange rates. Growth in US$ with constant exchange rates. Asia/Australia: includes China, India, Russia, Commonwealth of Independent States (CIS), SE Asia, Oceania and Japan. Contribution to growth may not add to 1% due to rounding.

6 TRANSFORMATIONS IN DISEASE TREATMENT 22 Specialty therapies continue to be more significant in developed markets than in pharmerging Spending in 218 Top 2 Classes 73% Others 27% Oncologics Diabetes Autoimmune Pain Respiratory Mental Health Hypertension Dermatology Cholesterol HIV Antivirals Viral Hepatitis Anticoagulants Other CNS Immunosuppressants Antibiotics Antiulcerants Vaccines Other cardiovascular Immunostimulants ADHD Developed Markets Sales in 218 (LC$) $71-81Bn $61-71Bn $47-52Bn $38-43Bn $33-38Bn $33-38Bn $27-3Bn $22-25Bn $21-24Bn $21-24Bn $21-24Bn $2-23Bn $19-22Bn $16-19Bn $15-17Bn $14-16Bn $13-15Bn $12-14Bn $1-12Bn $7-9Bn Specialty Source: IMS Institute for Healthcare Informatics, October 214; IMS Therapy Prognosis, October 214 The emergence of new therapies for hepatitis C have brought that therapy area into the top 2 for both developed and pharmerging countries. Oncology continues to be the largest category in developed countries, and the largest specialty area in pharmerging countries. CAGR % (-4)-(-1)% (-1)-2% 3-6% 36-39% 17-2% 11-14% (-3)-% (-5)-(-2)% (-1)-(-2)% (-3)-% Pain Antibiotics Hypertension Oncologics Diabetes Other Cardiovascular Antiulcerants Dermatology Cholesterol Mental Health Respiratory Immunostimulants Other CNS Viral Hepatitis Antiplatelets Womens Health Nasal Preps Anticoagulants Erectile Dysfunction Immunosuppressants Traditional Top 2 Classes 54% Others 46% Pharmerging Markets Sales in 218 (LC$) $19-22Bn $18-21Bn $16-19Bn $12-14Bn $11-13Bn $1-12Bn $1-12Bn $9-11Bn $8-1Bn $5-7Bn $4-6Bn $4-6Bn $3-5Bn $3-5Bn $3-4Bn $2-3Bn $2-3Bn $2-3Bn $1-2Bn $1-2Bn Leading classes in pharmerging markets are CAGR % 9-12% 1-13% 13-16% 9-12% 18-21% 8-11% 2-23% 1-13% 8-11% 14-17% 1-13% dominated by pain, antibiotics and hypertension, while in developed markets specialty categories such as oncology and autoimmune diseases are more prominent. Six of the top 2 classes in developed markets will face patent expiration in the next five years and therefore declining growth. Spending in US$ with variable exchange rates. Growth in US$ with constant exchange rates. Specialty therapies are defined by IMS as products that are often injectable, high-cost, biologic or requiring cold-chain distribution. They are mostly used by specialists, and include treatment for cancer and other serious conditions, and often involve complex patient follow-up and monitoring. Therapy forecasts from IMS Health Therapy Prognosis Global October 214 adapted by IMS Health Institute for Healthcare Informatics to represent global sales and to include additional therapy classes. Abbreviations: ADHD: Attention-Deficit Hyperactivity Disorder; CNS: Central Nervous System; HIV: Human Immunodeficiency Virus.

7 TRANSFORMATIONS IN DISEASE TREATMENT 23 Consistent high numbers of innovative and orphan medicines expected through 218 Global launch of new molecular entities (NMEs) 4 35 Global NME launches Average per year Novel mechanism Existing mechanism Orphan Source: IMS Institute for Healthcare Informatics, October 214 Through October 214, there have been 31 NMEs approved globally and 26 launched, six of which are classified as orphans in either the U.S. or E.U., and 18 are specialty products. In 214 there have already been 12 drugs approved in the U.S. that have FDA Breakthrough Therapy Designation, including the first biologic (meningococcal group B vaccine). Increasing numbers of orphan and breakthrough designation applications and steady approval rates are expected through the forecast period. New molecular entities include novel small molecule, biologic or novel combination products (where at least one of the ingredients is novel), launched for the first time globally. Novel mechanism therapies are those with novel mechanism of action applied for the first time in the approved indication. Existing mechanism therapies have mechanisms of action already used in their approved indication, though may still represent important clinical advances. Orphan therapies are approved for orphan-designated indications. molecular or biologic entity or combination where at least one element is novel.

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