wyeth 2006 Annual Review

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  • 1. Leading the Way to a Healthier Annual Review 2006 World
  • 2. Financial Highlights Year Ended December 31, 2005 2006 (In thousands except per share amounts) Net Revenue $18,755,790 $20,350,655 Net Income 3,656,298 4,196,706 Diluted Earnings per Share 2.70 3.08 Dividends per Common Share 0.94 1.01 Total Assets 35,841,126 36,478,715 Stockholders’ Equity 11,994,369 14,652,755 Wyeth at a Glance Wyeth is one of the world’s largest medicines and animal health care products research-based pharmaceutical and health that improve the quality of life for people care products companies. It is a leader in worldwide. The Company’s major divisions the discovery, development, manufacturing include Wyeth Pharmaceuticals, Wyeth and marketing of pharmaceuticals, biotech- Consumer Healthcare and Fort Dodge nology products, vaccines, non-prescription Animal Health. A Special Report On the Cover on Alzheimer’s Disease Contents Motivational life coach Meredith Millions of people around the 1 Chairman’s Report to Stockholders Froemke takes Enbrel for her world are coming face to face 7 Wyeth’s Pipeline for Innovation rheumatoid arthritis. “Within six with Alzheimer’s disease, a weeks of therapy, I felt like a new neurodegenerative disorder that 8 An Expanding and Promising human being,” she marvels. “It’s robs sufferers of their memories, Near-Term Pipeline given me back my mobility and my their identities and, ultimately, 12 The War on Alzheimer’s life.” Her daughter, Lauren, also their lives. Wyeth is at the forefront has benefited from an innovative of an extraordinary effort to 32 Selected Products from Wyeth Wyeth medicine after being find new and better medicines to vaccinated with Prevnar to help control this disease’s symptoms 33 Directors and Officers prevent invasive pneumococcal and, potentially, to halt or even 34 Financial Review disease. Wyeth is a leader in reverse its progression. A special innovation through use of report beginning on page 12 36 Corporate Data pharmaceutical, biotech and takes an in-depth look at Wyeth’s IBC Mission, Vision and Values vaccine technologies. war on Alzheimer’s.
  • 3. Chairman’s Report to Stockholders Robert Essner, Chairman and Chief Executive Officer am pleased to report that “We once again delivered on our • Revenue from all of our I 2006 was an excellent year biotechnology products in commitment to expand our for Wyeth. Building on our 2006 reached $5.7 billion, growth, strengthen our position strong performance in 2005, representing about a third we once again delivered on our of Wyeth Pharmaceuticals’ for the future and lead the way commitment to expand our total revenue and making to a healthier world.” growth, strengthen our posi- Wyeth the fourth largest tion for the future and lead biotechnology company in the way to a healthier world. the world. Driven by the steady growth of our key products, Wyeth • In January 2007, we received an approvable letter reported record revenue. We filed four New Drug Appli- from the U.S. Food and Drug Administration (FDA) cations (NDA) for new products, demonstrating solid for Pristiq, a serotonin-norepinephrine reuptake productivity from our research and development (R&D) inhibitor for the treatment of major depressive disor- efforts. Overall, our new product pipeline significantly der, which will be launched with a specific focus expanded and advanced. By maximizing productivity, on women. controlling costs and delivering high value, we helped • Wyeth Consumer Healthcare provided an important position Wyeth to address the economic realities of a revenue contribution and positioned itself for future changing health care environment. And, as we have growth through the introduction of innovative new done every year, during 2006 we continued to listen to products such as Advil PM. our stakeholders, to learn from them and to apply those • Sales for Fort Dodge Animal Health rose 6 percent, lessons to our business. driven by increased revenue from its companion Highlighted below are some of Wyeth’s significant animal and livestock products. The division’s robust achievements during 2006 and in early 2007. These new product pipeline is expected to continue as a demonstrate the success of our efforts and our potential source of strong growth. to build upon them: • We increased our dividend to stockholders for the • Wyeth’s 2006 net revenue increased 9 percent to second consecutive year, demonstrating the confi- nearly $20.4 billion, a record high for the Company. dence we have in our Company’s future and in the Pro forma earnings grew 14 percent, the second strength of its financial resources. consecutive year of double-digit growth. An in-depth In the section that follows this report, you will review of our 2006 performance is provided in read about how we’re striving to improve world health Wyeth’s 2006 Financial Report, the companion piece and sustain our growth through a near-term pipeline to this Annual Review. of innovative products. And in a special feature story • We achieved annual sales of more than $1 billion for on an area of enormous unmet need – Alzheimer’s each of six core product franchises: Effexor, Prevnar, disease – you will read about how Wyeth researchers Protonix, Enbrel, Wyeth Nutrition and the Premarin are seeking critical breakthroughs for patients, their family – demonstrating the breadth and diversity caregivers and society. of our portfolio. 1
  • 4. Wyeth Pharmaceuticals “Our pharmaceutical business Worldwide net sales for Enbrel, the number delivered outstanding results by ur pharmaceutical O one biotechnology product business delivered extending the reach of our products in its category in North outstanding results by America, grew 20 percent and enhancing their potential extending the reach of our to more than $4.4 billion. products and enhancing their for further growth.” This includes sales in the potential for further growth. United States and Canada At the same time, Wyeth that are recorded by our Pharmaceuticals took signifi- marketing partner Amgen Inc. While all regions con- cant steps to increase the efficiency and responsiveness tributed to growth, strongest results came from Europe, of its sales organization and to expand a variety of where sales increased 33 percent, making Enbrel educational efforts for patients. the number one ranked biotechnology product there. Effexor and Effexor XR continued as the world’s Wyeth Nutrition is a world leader in the develop- number one antidepressant franchise. Sales reached ment, manufacture and distribution of scientifically $3.7 billion in 2006, an increase of 8 percent. An based nutritional products for infants and toddlers. additional indication for use of Effexor XR in panic Wyeth Nutrition continued to grow at double-digit disorder contributed to growth while the results of rates in 2006. Global sales grew to $1.2 billion, an the PREVENT study provided further evidence of the increase of 15 percent over 2005. The two regions sustained efficacy of Effexor XR in treating major enjoying the fastest growth were Asia/Pacific, which depressive disorder. comprised nearly 60 percent of global nutritional sales Prevnar (Prevenar outside the United States) was and grew 23 percent, and Latin America, which made the number one selling vaccine in the world, with up 16 percent of global sales and grew 15 percent. 42 million doses manufactured and net sales of nearly Having recently celebrated its 90th anniversary, $2 billion, an increase of 30 percent over 2005. Strong Wyeth Nutrition has evolved into a significant interna- global usage of Prevenar accelerated in 2006 as nine tional player with 60 affiliates selling our products more countries, including Germany, Mexico and around the world. The Company markets its premium the United Kingdom, added Prevenar to their National product line under the Gold banner and, in late 2006, Immunization Programs (NIP). In total, 16 countries was first to market with an innovative new product have incorporated Prevenar into their NIPs, and called Gold with lutein, which seeks to protect the eyes growing evidence of the vaccine’s high value creates of infants. To meet increasing demand for providing opportunities for further expansion. infants and toddlers with high-value products like the Protonix, for erosive acid reflux disease, grew Gold line, Wyeth Nutrition increased its manufacturing 7 percent to approximately $1.8 billion. During the capacity in Mexico and began construction of an year, RENEW, an innovative patient educational expanded facility in the Philippines. program for Protonix, was launched, providing sample starter medications and educational materials to facilitate discussions between patients and their physi- cians and to help ensure patient compliance over the longer term. 2
  • 5. Wyeth remained a global leader in hormone Three growth drivers – Advil, Centrum and therapies and was the U.S. market leader as sales of the Caltrate – benefited significantly from this strategy. Premarin family of products increased 16 percent The Advil franchise grew 7 percent around the world, globally and 21 percent in the United States. New data largely fueled by new marketing efforts. In Canada, published in 2006 helped to further clarify the benefits Advil increased its market share and became the leader and risks of hormone therapy for women, and Wyeth in the analgesic category for the first time. The Cen- currently is working with physicians and their patients trum family of vitamin products achieved 4 percent to appropriately address patient needs based on the sales growth, driven by innovations in Europe and emerging data. growth in the age 50+ population. Centrum Advantage Zosyn (Tazocin outside the United States) contin- was launched in the Canadian market in 2006. ued to be the largest selling I.V. antibiotic worldwide Caltrate grew 3 percent largely due to international with global net sales of $972 million, a 9 percent expansion. increase over 2005. The success of Zosyn is attributa- Overall, international sales increased 2 percent ble to its clinical efficacy and its ability to help while U.S. sales declined 3 percent. The decline in hospitals control the emergence of resistant bacteria. the United States primarily resulted from the ongoing Tygacil, our new antibiotic product, also delivered net impact of legislative restrictions on sales of pseu- sales growth during the year. Since its launch in 2005, doephedrine-containing cough/cold formulations. In it has gained 55 worldwide regulatory approvals response to these restrictions, Wyeth Consumer and now is available in 33 markets. Tygacil is particu- Healthcare transitioned most of its products to an larly important in hospitals for patients infected alternative active ingredient. This reformulation is with common as well as more dangerous resistant expected to impact sales favorably in 2007. Outside infectious pathogens in complicated skin/skin- the United States, a number of major international structure and intra-abdominal infections. markets enjoyed double-digit growth, including All these products require the right selling model Canada, China, Colombia, Mexico, Portugal, Taiwan, for a changing health care environment. We’re pleased Thailand and Venezuela. to report that the new primary care selling model we Wyeth Consumer Healthcare was particularly implemented in the United States last year is working successful in achieving operating efficiencies to fund well. In 2006, we jumped from No. 8 to No. 1 in the new investments and increase net income. Innovation Health Strategies Group’s annual primary care physi- also was a key contributor to growth, highlighted by cian audit, which demonstrates physicians’ initial the successful launch of Advil PM. Opportunities satisfaction with our new structure. for future growth now are being developed, including an innovative Caltrate food-grade line in China, the start of a consumer health care business in Russia, Wyeth Consumer Healthcare and an intense research and development effort to xcluding the impact of revenue from Solgar E deliver new forms of Advil. Vitamin and Herb, which was divested in 2005, sales for Wyeth Consumer Healthcare increased 1 percent to more than $2.5 billion in 2006, spurred largely by a strong focus on supporting our core global brands. 3
  • 6. Fort Dodge Animal Health capture, and the simplification of clinical trial material shipments and processes through a strategic alliance ales of our Fort Dodge Animal Health products S with a leading, worldwide logistics provider. moved closer to $1 billion, reaching $936 million We continued to realize solid results from our and increasing 6 percent over the prior year. In R&D organization, drawing upon our expertise in three 2006, Fort Dodge received pan-European regulatory distinct discovery platforms: small molecules, biologics approval to market ProMeris/ProMeris Duo, products and vaccines. In 2006, Wyeth filed NDAs for Viviant, offering flea and tick protection for dogs and flea protec- for prevention of postmenopausal osteoporosis; Pristiq, tion for cats. Approval in the United States is expected for non-hormonal treatment of moderate to severe in the first half of 2007. Another key achievement was vasomotor symptoms associated with menopause; the U.S. launch of Suvaxyn PCV2 One-Dose, a vaccine Torisel, for patients with advanced renal cell carcinoma, for the prevention of porcine circovirus, a disease that which received priority review status; and bifeprunox – leads to a wasting syndrome in pigs. In the face of global filed with our partner Solvay Pharmaceuticals – for the concerns over avian influenza, Fort Dodge received treatment of schizophrenia. In addition, we submitted approval for Poulvac Flufend, a new inactivated reverse regulatory applications for a reformulation of BeneFIX, genetics vaccine for poultry that addresses the potential one of our hemophilia agents, as well as for a new adult pandemic strain of the avian influenza virus. granule-dose formulation of Protonix, and we received regulatory approval for new dosing recommendations Research and Development for Rapamune in high-risk renal transplant patients. ur greatest challenge at Wyeth is to create O Wyeth also is seeking to expand its presence in the con- breakthrough medicines that serve the needs traceptive market with Lybrel, currently awaiting final of patients in an increasingly competitive envi- FDA approval. Lybrel is a novel, continuous-use oral ronment. From a research and development standpoint, contraceptive that is designed to provide significant that challenge requires thinking and acting differently benefits in terms of menstrual-cycle regulation. in discovering and advancing to market potentially During the year, we successfully advanced 15 new important compounds. That is why we have instituted a molecular entities and two new vaccine constructs new Learn and Confirm paradigm for drug development from discovery into development. In total, over the past – a two-phase approach to streamlining the traditional six years, 75 new drug candidates were placed into devel- multiple phases of development. This effort places opment, the majority having potential to be first- or greater emphasis on high-performing teams, rapid best-in-class therapies. That has made Wyeth a leading decision making and improved clinical trial designs. company within our industry peer group in discovering Other accomplishments include the creation of a global novel molecules and advancing them rapidly into clinical network of 10 early clinical development centers to development. We also believe that our pipeline is among optimize our global patient mix, the streamlining of the most robust in the industry. Others share our positive clinical data collection processes using electronic data views. For example, early in 2007, R&D Directions magazine recognized Wyeth as the company with the best central nervous system product pipeline in the industry. 4
  • 7. In 2007, we expect to “We continued to realize solid results Success will come not submit several important just in the laboratory from our R&D filings, including Viviant, for but also on the regulatory organization, drawing upon the treatment of osteoporosis; front and through the Aprela, for the treatment development of strong part- our expertise in three of menopausal symptoms and nerships with patient distinct discovery platforms …” prevention of postmenopausal groups, government, regula- osteoporosis; methylnaltrex- tory agencies, and scientists one subcutaneous, for opioid- in industry and academia. induced constipation in advanced medical illness; We must encourage additional research, accelerated and methylnaltrexone I.V., for post-operative ileus; and informed new drug reviews, and more aid to caregivers Tygacil, for use in community-acquired pneumonia and who bear the brunt of this health scourge. You will read hospital-acquired pneumonia. about some of the patients and their caregivers in this report. These family members are courageous beyond measure in doing everything in their power to try to care A Special Report on Alzheimer’s Disease Research for their loved ones at home. believe that Alzheimer’s disease is the biggest health I care issue of my generation. More than 4.5 million The People of Wyeth Americans suffer today, and, as the baby boomer generation ages, it is expected that this number will ur Company has exhibited a track record of O grow substantially. Add to that millions more affected consistency, performance and responsibility. by the disease – the families and caregivers of Alzheimer’s The people of Wyeth know that to continue patients – and the billions of dollars in health care costs on this path, we must maintain a relentless focus borne by society, and the nature of the challenge and on improving our Company and running it even more the critical importance of doing everything we can to efficiently. Our people understand that we have an overcome it become clear. Clinical research in this field imperative to change Wyeth fundamentally in order is complex and expensive with outcomes uncertain, to succeed in the years ahead. At its core, this effort is but the impact of success would be enormous. based on two simple ideas. First, every year we will We’re proud that Wyeth is at the cutting edge in aim to grow our revenue through the quality of our seeking new drugs not only to treat Alzheimer’s disease products and their value to the people we serve. And symptoms better than currently available therapies but second, every year we will aim to grow our profit at potentially to stop or even reverse the course of this a faster rate than our revenue by running our Company crippling and ultimately fatal disease. Our goal is to turn more efficiently and productively. These goals drive the corner on this terrible illness and provide new hope. our results and determine how they are evaluated and how we plan to improve upon them in the future. Wyeth Research and Development Expenses Wyeth’s New Product Pipeline ($ in billions) 2001: 49 projects 2006: 77 projects ’06 3.11 LCM 2.75 ’05 LCM 22% NME 45% ’04 55% 2.46 NME 78% ’03 2.09 NME = New molecular entity LCM = Life cycle management 5
  • 8. Changes in Management valued at $160 million, to 250,000 Americans who were without adequate prescription drug coverage or am pleased that we have continued to strengthen the I insurance. Outside the United States, we worked to sup- leadership of our organization in a variety of ways. port maternal health care, ensure access to reproductive In October 2006, we welcomed Raymond J. McGuire and child health resources, and develop a new treatment to our Company’s Board of Directors. Mr. McGuire is option for river blindness. We are working with the a Managing Director and Co-Head, Global Investment Global Alliance for Vaccines and Immunization to find Banking, for Citigroup Global Markets Inc. I know he an affordable and sustainable way to bring vaccines to will provide important perspectives on our business oper- children in the developing world. We also are working ations and strategy. In January 2007, Bernard Poussot hard to help protect and enrich the environment in was elected Chief Oper- the communities where we live and work by steadily ating Officer of Wyeth reducing environmental emissions and ensuring the and joined the Com- safety of employees at all of our facilities. pany’s Board of Direc- tors. Earlier in 2006, he Looking to the Future was promoted to Presi- dent and Vice Chairman s we look to the future, we know that we will A of Wyeth. In his more be operating in a tough environment around than 20 years with our the world. To compete, we will continue Company, Mr. Poussot’s to attract, retain and engage a diverse workforce that leadership has helped us broadens our perspectives, enhances our customer transform our organiza- connections and increases our creativity. The more pro- tion and set it on a ductive and innovative we are in our operations, the course for continual better we will be in addressing concerns about pricing growth. Also in 2006, and access to our medicines. Kenneth J. Martin was We have made important progress in a relatively short promoted to Chief time as part of a longer-term effort to find new and more Kenneth J. Martin, Chief Financial Financial Officer and efficient ways to meet the challenges of the 21st century. Officer and Vice Chairman, left, and Vice Chairman of The momentum we now have can be accelerated. We Bernard Poussot, President, Chief Wyeth. In addition to will continue to foster a high-performance culture where Operating Officer and Vice Chairman. heading our finance every person has a role, every person takes responsibility organization, Mr. Martin took on responsibility for our and every person acts to make a difference. We will infrastructure initiative, which is critical to our operating continue to execute against aggressive plans and develop efficiency and, therefore, to our future success. Further systems to help ensure both success and compliance with supporting our management team, Joseph M. Mahady the highest legal and ethical standards around the world. was named President – Global Business for Wyeth Phar- And we will foster innovation through our creativity, maceuticals and continues as a Senior Vice President of challenging what we do every day and seeking improve- Wyeth. In his new role, Mr. Mahady assumes operational ments and opportunities for the years ahead. Our goal, responsibility for Wyeth’s global pharmaceutical business. over the next decade, is to make Wyeth a stronger With this expanded responsibility, I am certain he will company with an even higher value portfolio of prod- bring significant insights to our worldwide business and ucts to fuel growth. commercial portfolio. In addition, Geno J. Germano was I want to take this opportunity to thank the people named President and General Manager, Wyeth Pharma- of Wyeth for making a difference for our Company ceuticals – United States and Wyeth Pharmaceutical and those we serve. Thanks to their efforts, our growth Business Unit. Robert E. Landry, Jr., was elected Treasurer has accelerated, our pipeline never has been stronger and of Wyeth. we are on the path to deliver important new medicines to a world in great need. Corporate Social Responsibility yeth recognizes its significant responsibilities W as a global corporate citizen. One of the most Robert Essner important actions we can take in this regard Chairman and Chief Executive Officer is to expand access to our medicines. Our patient assis- February 26, 2007 tance programs in 2006 provided free Wyeth medicines, 6
  • 9. Wyeth’s Pipeline for Innovation Since 2004, Wyeth has submitted 11 New Drug Applications (NDA) in the United States, delivering on our goal of filing two NDAs for new molecular entities a year. And, over the past six years, 75 new drug candidates were placed into development, the majority having potential to be first- or best-in-class therapies. This chart presents a snap- shot of new drugs from Wyeth that currently are in human trials or are being reviewed by regulatory agencies. Phase 3 Phase 2 Regulatory Review Phase 2 Phase 3 Regulatory Review Women’s Health and Bone Vaccines and Infectious Disease Lybrel (levonorgestrel/EE) ™ Continuous contraception 13-valent pneumococcal conjugate vaccine Premenstrual dysphoric disorder Prevention of pneumococcal disease in Pristiq™ (desvenlafaxine succinate) infants and children 6 months to 2 years Vasomotor symptoms of menopause Prevention of pneumococcal disease in Viviant™ (bazedoxifene) high-risk individuals and adults > 50 Postmenopausal osteoporosis prevention Tygacil® (tigecycline) Postmenopausal osteoporosis treatment Community-acquired pneumonia Aprela™ (bazedoxifene/conjugated estrogens) Hospital-acquired pneumonia Postmenopausal osteoporosis Resistant pathogens Vasomotor symptoms of menopause HCV-796 Dibotermin alfa (rhBMP-2) injectable Hepatitis C Closed fractures Meningococcal B vaccine Prevention of meningococcal disease in Neuroscience adolescents Bifeprunox Inflammatory Disease Schizophrenia (U.S.) Bipolar disorder TRU-015 Effexor XR® (venlafaxine HCl) Rheumatoid arthritis Major depressive disorder (Japan) Pristiq™ (desvenlafaxine succinate) Oncology/Immunology/ Major depressive disorder Hemophilia Fibromyalgia BeneFIX® (coagulation factor IX – Neuropathic pain recombinant) Bapineuzumab (AAB-001) Reformulation – hemophilia B Alzheimer’s disease Mylotarg® (gemtuzumab ozogamicin) Lecozotan (SRA-333) Relapsed acute myeloid leukemia (EU) Mild to moderate symptoms of Torisel™ (temsirolimus) Alzheimer’s disease Renal cell carcinoma Vabicaserin (SCA-136) Mantle cell lymphoma Schizophrenia Rapamune® (sirolimus) Conversion in liver transplant Gastrointestinal/Metabolic ReFacto® AF (antihemophilic factor – Protonix ® (pantoprazole sodium) recombinant) Adult granules formulation Hemophilia A Methylnaltrexone Bosutinib (SKI-606) Subcutaneous for opioid-induced Breast cancer, chronic myeloid leukemia, constipation in advanced medical illness pancreatic cancer, non-small cell I.V. for post-operative ileus lung cancer Oral for opioid-induced constipation HKI-272 PPM-204 Breast cancer, non-small cell lung cancer Type 2 diabetes Phase 2 Phase 3 Regulatory Review Determination of safe Determination of overall Evaluation of safety and effective dosage for benefit/risk ratio for an and efficacy data an experimental medi- experimental medicine, by governmental cine, generally conducted generally conducted in regulatory agencies in hundreds of patients thousands of patients 7
  • 10. Positioned for Growth: An Expanding and Promising Near-Term Pipeline Important New Drugs Projected for Filing through 2007 Women’s Health Care A t Wyeth, many important new Viviant Aprela drugs have (bazedoxifene) (bazedoxifene/conjugated estrogens) been filed with regulatory Viviant, a selective estrogen receptor During 2007, Wyeth is planning to authorities or are in late- modulator, is undergoing regulatory file an NDA for Aprela for the treat- review for the prevention of post- ment of vasomotor symptoms and stage clinical development, menopausal osteoporosis while vaginal atrophy and for the preven- encompassing treatments continuing in Phase 3 clinical trials tion of osteoporosis, three major for the treatment of postmenopausal complications of menopause. Aprela that span a variety of osteoporosis. The National Osteo- represents the first Tissue Selective therapeutic areas, including porosis Foundation estimates that Estrogen Complex product and approximately 8 million women in seeks to provide the most compre- women’s health care, the United States hensive therapy neuroscience, cancer and have osteoporosis for menopause and another 22 mil- as well as a infectious disease. lion are at risk for new paradigm . developing this for treatment disease. Each year, of osteoporosis. osteoporotic frac- The addition tures cost the coun- of conjugated try’s health care estrogens to system an estimated bazedoxifene $18 billion. for the relief of In August 2006, a wide range the U.S. Food and of menopausal Drug Administration symptoms (FDA) accepted the (including hot Viviant New Drug flushes) is Application (NDA) expected to add for the prevention significant value of osteoporosis. In for patients, 2007, Wyeth plans potentially to submit an additional NDA for making the bazedoxifene family a Viviant for the treatment of osteo- comprehensive approach to treat- porosis. If approved, Viviant will ment of postmenopausal vasomotor represent the first new agent in symptoms and postmenopausal its class in nearly 10 years and will osteoporosis. provide physicians with a new option for patients at risk of osteo- porosis and fracture. 8
  • 11. Pristiq Lybrel (desvenlafaxine succinate) (levonorgestrel/ethinyl estradiol tablets) Pristiq, a serotonin-norepinephrine reuptake inhibitor, is being developed Lybrel is an investigational oral with a specific focus on women. contraceptive that contains a The product will have two indica- well-studied combination of low- tions: the treatment of major dose levonorgestrel and ethinyl depressive disorder and the relief estradiol. Pristiq also has of moderate to severe vasomotor If approved, been studied for the symptoms associated with it is expected treatment of hot menopause. to be the flushes associated with Pristiq is expected to improve only combi- menopause, and the balance of serotonin and norepi- nation oral marketing applications nephrine relative to that provided contraceptive for this use were filed by serotonin reuptake inhibitors indicated for with the FDA and the because of its pharmacologic profile continuous European Medicines as a dual reuptake inhibitor. This usage, 365 Agency in 2006. If balance is thought to be important days a year, approved, Pristiq in depressed women who, when without a will be the first non- transitioning through menopause, placebo phase hormonal treatment often experience a fluctuation or or a pill-free indicated for the decline in estrogen that may directly interval. relief of vasomotor or indirectly diminish both serotonin This product, symptoms. and norepinephrine functioning. when taken Additional clinical consistently, trials now are under is designed to way to evaluate the effectiveness make it possible for many women and safety of Pristiq as a treatment to eliminate the bleeding associated for fibromyalgia syndrome and with the menstrual cycle while pro- diabetic neuropathic pain. NDA viding effective contraception. In the filings for these two indications United States, an approvable letter may occur as early as 2009. for Lybrel was received from the FDA in June 2006, and, in the Euro- pean Union, the marketing applica- tion for Lybrel, under the trade name Anya, also is being reviewed. 9
  • 12. Neuroscience Cancer Torisel Bifeprunox leukemia (CML). CML accounts for (temsirolimus) between 15 percent and 20 percent of all adult leukemia cases in West- An NDA for bifeprunox for the Torisel is a specific inhibitor of ern populations. treatment of schizophrenia was mTOR (mammalian target of submitted to the FDA in October rapamycin), a signaling protein that 2006. Wyeth co-develops and co- regulates cell growth and new blood promotes bifeprunox in the United vessel formation. U.S. and EU filings States, Canada and Mexico with for Torisel were submitted in Octo- Solvay Pharmaceuticals. ber 2006. It is undergoing priority The safety data for bifeprunox U.S. regulatory review and received consistently have shown a favorable fast track status for the treatment of weight and metabolic profile in advanced renal cell carcinoma both short- and long-term studies. (RCC). Torisel currently is in clini- Weight gain is a common and cal trials for several other cancers, serious side effect of older atypical including mantle cell lymphoma. antipsychotics and can cause RCC accounts for about 85 per- patients to stop taking their medica- cent of all renal cancers. Patients tion. While bifeprunox has been with the most advanced form of the shown to have a smaller mean effect disease have a five-year survival rate in acute psychosis when compared of less than 20 percent. Recently, with older atypical antipsychotics, Wyeth reported data showing that HKI-272, also in Phase 2, is a cell it may be especially useful in patients who were treated with tem- signaling inhibitor that focuses on stabilized patients who need to be sirolimus alone experienced a 49 inhibiting tumor cell growth. This maintained on therapy over the percent increase in median overall agent targets a specific growth fac- long term because of its favorable survival time compared with tor receptor signaling molecule, metabolic profile. patients treated with interferon- HER-2, which is found on the sur- alpha alone. In addition to improv- face of some breast cancer cells. It is ing overall survival, Torisel being studied in advanced breast preserved a patient’s quality of life, cancer patients who have failed potentially helping treated patients standard therapy. Early clinical live longer and feel better. data from these very early and very small trials show encouraging Other Oncology Compounds patient responses, including shrink- in Development age of breast and lung tumors. CMC-544 or inotuzumab, Wyeth’s pipeline contains several currently in Phase 1, is using a novel innovative cancer compounds that approach called antibody-targeted are in the middle stages of develop- chemotherapy. Mylotarg, also from ment and are expected to advance to Wyeth, uses similar technology larger clinical trials. and currently is indicated for the SKI-606 or bosutinib, currently in treatment of acute myelogenous Phase 2, is a cell signaling inhibitor leukemia. CMC-544 initially is that targets critical growth path- being developed for treatment of ways in cancer cells that allow cells non-Hodgkin’s lymphoma. to divide. Clinical trial data thus far show activity in imatinib-resistant patients with chronic myelogenous 10
  • 13. Gastrointestinal Infectious Disease and Metabolic Vaccines Methylnaltrexone Tygacil Prevnar 13 (tigecycline) (13-valent pneumococcal Opioid analgesics, such as mor- conjugate vaccine) phine, are among the most widely Tygacil was launched on a global used medicines to treat patients with basis in 2005 for the treatment Since the introduction of Prevnar moderate to severe pain. However, of complicated skin and abdominal pneumococcal 7-valent conjugate their use often results in opioid- infections. Developed as an vaccine in the United States, the induced constipation or OIC, a expanded, broad-spectrum antibi- Centers for Disease Control and common and serious side effect that otic for patients with acute infec- Prevention estimates that invasive can be a barrier to effective pain tions who are admitted to a pneumococcal disease (IPD) management. The constipation can hospital, it offers a high likelihood addressed by the Prevnar serotypes be severe enough to require tempo- of effective treatment when the has been reduced 94 percent in rary discontinuation of the needed pathogen causing an infection is children and 55 percent in adults. opioids – thus leaving the patient unknown and, more important, In addition, the rate of antibiotic- with inadequate pain relief – or when certain resistant pathogens resistant IPD has decreased substan- surgical intervention. Every year, an are suspected. tially in infants and young children estimated 5 million patients suffer Tygacil also was developed to and in adults over age 65. from OIC in the United States alone. combat gram-positive resistant There currently is no approved bacteria, including resistant Staphy- medication that specifically targets lococcus aureus, and gram-negative the cause of OIC without interfering bacteria, including ESBL-producing with pain relief. Klebsiella pneumoniae. It represents Methylnaltrexone is a selective a new weapon in the global battle opioid antagonist being studied as against antibiotic resistance. a treatment to block the peripheral Wyeth is targeting an NDA side effects of opioid analgesics. filing for Tygacil in 2007 to include The drug is designed to reverse OIC community-acquired pneumonia, rapidly and consistently without hospital-acquired pneumonia and reversing analgesic effects or additional evidence of effectiveness inducing withdrawal symptoms. in the treatment of infections caused Methylnaltrexone is being by certain atypical pathogens. developed in subcutaneous and oral Hospital-acquired pneumonias are dosage forms as first-in-class treat- of particular importance because Building on this significant ment platforms for OIC. It also is of the relatively high rate of morbid- advance in public health, Wyeth is being developed in an intravenous ity and mortality associated with developing Prevnar 13, a 13-valent (I.V.) form for post-operative ileus, this condition. In addition, resistant pneumococcal conjugate vaccine that a potentially serious impairment of organisms are becoming more targets 13 strains of S. pneumoniae. gastrointestinal function that can prevalent in pneumonia, further This new vaccine currently is under- delay surgical recovery and prolong increasing the risk of mortality. going worldwide Phase 3 trials in hospitalization. both children and adults, with regu- Wyeth is developing methylnal- latory submissions expected to begin trexone in collaboration with in 2009. If approved, Prevnar 13 Progenics Pharmaceuticals, Inc. The would be the most complete vaccine companies plan to submit NDAs available for the prevention of pneu- for subcutaneous methylnaltrexone mococcal disease and otitis media in in early 2007, I.V. methylnaltrexone young children. For adults, Prevnar in late 2007 or in early 2008 and 13 is expected to extend protection to oral methylnaltrexone in late 2008 persons age 50 and older and to pro- or early 2009. vide them with long-term protection. 11
  • 14. THE WAR on Alzheimer’s “ ach morning, for more years than I wish to caregivers are added to the toll. Treatments cost E remember,” says Meryl Comer, a 62-year- the U.S. health care system more than $100 billion old award-winning broadcast journalist, annually. In the next 20 years, the number of “I reintroduce myself to my husband, Harvey. victims will increase sharply, with the potential to I say, ‘Good morning, love. My name is Meryl. bankrupt our health care system. “There are no I am your wife. We’ve been married for 25 years. cures, no remissions,” says former Speaker of Don’t worry. This is your home. And you are the U.S. House of Representatives and Center for safe.’ His eyes are blank, and mine fill with tears.” Health Transformation founder Newt Gingrich. Dr. Harvey Gralnick, once a leading researcher “You won’t meet an Alzheimer’s survivor because at the National Institutes of Health, has had there are none. The need for medical break- Alzheimer’s disease for 12 years. Meryl, his throughs never has been greater.” caregiver, has been suffering for just as long. Wyeth is on the leading edge of potential Dr. Gralnick is among 4.5 million Americans breakthroughs, having declared an all-out war with Alzheimer’s disease. In the United States, it on the disease. This special report introduces strikes one of every 10 people over age 65 and the faces of Alzheimer’s, the weapons being nearly half of those over age 85. About 18 million developed and the battles that still need to be people suffer worldwide – millions more when waged – and won. 12
  • 15. “Good morning, love. My name is Meryl. I am your wife …” 13
  • 16. Understanding the Enemy A Primer on Alzheimer’s Disease ne hundred years on ways to inhibit tangles, O after Alois though many scientists Alzheimer, a now believe that these German psychiatrist and form later in the disease neuropathologist, first process – perhaps driven characterized the plaques by the amyloid deposition. and tangles in the autop- Symptoms of sied brain of a victim Alzheimer’s disease of this crippling and ulti- include loss of memory – mately fatal degenerative first short term and disease, researchers eventually the ability to still are not fully certain remember the past or what causes Alzheimer’s create new memories; This photomicrograph shows the outermost layer of the brain of or exactly what the right difficulty in speaking and an Alzheimer’s disease sufferer. The red-colored accumulations are beta-amyloid plaques. strategy is to defeat it. reading; disorientation; “Alzheimer’s disease and, ultimately, loss of was widely misunder- capacity to dress, bathe secretase – cut this protein insoluble in some people stood for many years,” or perform what com- in certain ways, normal after six decades of being says Sid Gilman, M.D., monly are called activities amyloid transforms into fluid. The aggregation, professor and Chair of of daily living. Says beta-amyloid peptide. for whatever reason, leads the Department of Neu- Dr. Gandy: “Over time, It becomes sticky and to a misfolding of the rology at the University of all of the outside surface aggregates together in the protein. And once it takes Michigan and Director of of the brain, all of the brain. Eventually, these shape as what basically is the Michigan Alzheimer’s cerebral cortex – the part aggregates accumulate a bobby-pin-like structure, Disease Research Center that’s responsible for between the nerve cells in it becomes locked in that there. “As people aged, thinking – degenerates, parts of the brain respon- structure and accumulates, it was widely believed and patients die bed- sible for memory and forming amyloid plaques. that they simply lost their bound in a vegetative judgment. As that happens, you see memory. Today, some state.” Samuel Gandy, M.D., the characteristic lesions of physicians still think Joel Ross, M.D., has Ph.D., Chair of the Alzheimer’s disease.” memory loss is normal as been a practicing geriatri- National Medical The other you grow older. That’s cian and internist for the and Scientific abnormal pro- not so. You should retain past 20 years and has seen Advisory tein that your memory until you some 1,000 Alzheimer’s Council of the appears in die. Alzheimer’s is a dis- patients during that time. Alzheimer’s the disease is ease process, and aging is “Anger and depression Association, called tau, just one risk factor.” are common in early notes, “The which accu- What may be the disease. Psychosis is not amyloid mulates in primary culprit? Many unusual in later disease. peptide nor- the cells researchers believe it is the And the wandering we mally is found themselves, toxic form of a protein – sometimes see is a func- between nerve leading to the called amyloid precursor tion of disorientation cells in your tangles that protein – that appears and lack of memory.” blood or in your Dr. Alzheimer first naturally in small quanti- spinal fluid. The chal- saw. The tangles develop ties in our bodies. When lenge is why it becomes inside the nerve cells, two enzymes – gamma Left: This CT scan of a brain eventually killing them. shows the atrophy caused by secretase and beta Some drugs are focusing Alzheimer’s disease. 14
  • 17. “I would do anything to keep him Memory problems and confusion at his last job as a chemical salesman contributed to his employment being just the way he is today.” terminated in April 2005. Ted explains: “I made a lot of my sales calls by phone, but I couldn’t remember exactly what people had said to me after I hung up. I was taken June and Ted Roderick: They’re a Couple out of sales and put in other jobs. Was it fair? It’s hard to say.” J une and Ted Roderick are at the leading edge of the Ted finds humor a good defense mechanism. “Actu- baby boomer generation – a time when many think ally, it’s a good excuse if I don’t want to do something about retirement, new hobbies, vacation plans, grand- around the house. I can say, ‘I forgot.’ They’re the children. But June and Ted are too preoccupied for two words I use most.” But sometimes it’s hard. “June that. Ted, age 63, has Alzheimer’s disease and has had will arrive home and ask what I did during the day. it for at least six years. I know I did things, but I don’t know what they were. “We’re fortunate because Ted continues to function It’s frustrating.” at a high level,” his wife June says. “He’s still driving June says, “You take every day and appreciate what and can read short articles in the newspapers and you have. I would do anything to keep him just the magazines.” way he is today. We’ve been married 40 years. I hope Ted also can take apart a faucet and put it back we can continue the way we are. together and make screens for storm windows. He says, “We worry about losing each other,” she adds. “That’s “I feel more competent doing mechanical tasks than why we keep fighting and trying to do everything we mental things. I just forget stuff.” And he speaks ration- can to prevent the disease from getting worse. We won’t ally about his disease. “I can’t remember what I did stop. We do everything together. You see, we’re a couple. an hour ago or yesterday. It’s annoying, but, for now, And we want to stay a couple.” it’s not debilitating.” 15
  • 18. William Utermohlen, an American artist living in London, chron- icled the progression of his Alzheimer’s disease in a series of self-portraits, several Changes in personality Dr. Gandy says, a series of biomarkers, of which are shown also can include anxiety “the medicines or proteins, whose pres- here. The top painting, and apathy or even suspi- we have today ence in the blood or spinal completed shortly after he learned he had the ciousness, agitation or wear off and fluid may indicate the disease, is followed by delusion. With the passing aren’t effective. disease already is at work. others he created as of time, victims may lose They don’t “I would advocate the disease pro- their ability to swallow appreciably slow starting a therapy when gressed and affected his abilities and per- and eat solid foods or the progression amyloid is just beginning ceptions. Today, Mr. become incontinent. of the disease to be deposited – before Utermohlen resides in Often they die from the and don’t attack significant symptoms a nursing home and consequences of being the underlying occur,” adds Ronald Black, no longer paints. bedridden or sustaining pathology.” M.D., Senior Director, a physical injury, like a Most researchers Neuroscience Clinical broken hip. Many don’t now believe Development at Wyeth. at risk factors recover, in part, because toxic amyloid “That is the promise and treat at least a they can’t remember they and tau begin of prevention. It parallels decade in advance are sick or had an accident forming years treatment of breast of cognitive decline. and can’t understand before symptoms cancer: Detect and treat The reason for directions for therapies appear. So even at an early stage.” that length of time to help them get better. as researchers Wyeth is participating is because Mother “We believe there is begin to seek in the Alzheimer’s Disease Nature is very a genetic basis for this new treatments Neuroimaging Initiative, careful. There is so disease,” says Dr. Gilman. for Alzheimer’s, a five-year public/private much redundancy Having the gene called they are focusing partnership that has in the brain that Apolipoprotein E4 puts on how to diag- brought together industry, one has to lose one at greatest risk, often nose the disease academia and the National huge numbers of predisposing a person to at its earliest Institutes of Health to nerve cells before develop the disease sooner possible stages. validate biomarkers and symptoms develop.” rather than later. “If you The basic principle, develop new neuroimag- Standard psychologi- look at the universe of Dr. Gandy notes, “is to ing tools. cal testing, coupled with Alzheimer’s patients,” he target the disease before How do physicians imaging, is about 80 per- adds, “50 percent have permanent damage help patients when so few cent to 90 percent accurate the ApoE4 gene.” to neurons occurs. Part therapies are available? in diagnosing the disease Included among of the reason to target Among other things, and staging it – from mild known physical aspects amyloid is that it is felt “We encourage them to to moderate to severe. of the disease is the loss to accumulate early in participate in our clinical Diagnosis also includes of nerve cells that use the the disease cascade. Once trials for their own sake ruling out other possible neurotransmitter acetyl- there is an effective ther- and for the sake of others physical or psychological choline, a chemical that apy that treats early stages afflicted with this devastat- causes that may be more these cells use to commu- of the disease, the field ing disease,” Dr. Gilman treatable, such as severe nicate with each other. will try to identify patients says. “I tell them what depression, alcoholism, Nearly all the currently earlier and earlier. We they can expect next. thyroid malfunction, approved medicines target hope this information will I prepare them as best I brain traumas or stroke. this aspect of the disease. lead to prevention of can. At least today, we Scientists are making However, as Alzheimer’s Alzheimer’s by identifying have great hope for better progress toward develop- progresses and nerve patients most at risk.” treatments – more than ing simpler tests for the cells become impaired to Dr. Gilman agrees: ever before. This is the disease by identifying the point of degenerating, “It would be ideal to look dawn of a new age.” 16
  • 19. Creating Hope New Therapies from Wyeth Move to the Frontlines or the past 15 years, “Programs have moved from ideas “Wyeth is fully commit- F Wyeth’s research ted to our Alzheimer’s in people’s minds to agents in has been focused programs, and we will clinical testing. This has been a on finding new and better continue to do our part to treatments for Alzheimer’s try to harness scientific huge effort on all fronts.” disease. The science has advances to overcome advanced, and the disease Alzheimer’s disease and researchers are working been a huge effort on process has become better improve the lives of exclusively on the all fronts.” understood. And as patients and families.” disease. And about 2,700 With 23 projects at animal models have been In addition to devel- researchers, or 40 percent various stages of develop- developed to mimic cer- oping drugs to control of Wyeth’s total R&D ment, from early discovery tain aspects of the disease symptoms more effec- staff, have been or to late-stage clinical trials, and thus can be used to tively than those currently presently are involved in Wyeth is the only major test new therapies, this available, the Company some aspect of the Com- pharmaceutical company work has taken on an is expending significant pany’s work in this area that uses increased sense of urgency of clear and significant all available as well as possibility. unmet medical need. technology In 2000, that research Menelas Pangalos, platforms in effort accelerated signifi- Ph.D., is Vice President of its develop- cantly when Wyeth Neuroscience Research ment efforts. entered into a partnership at Wyeth. “We’ve more These include with Elan Corporation to than doubled our small mole- utilize antibodies to allow resources in Alzheimer’s cules or tradi- the body to fight the poi- disease research in the tional drugs, sonous amyloid involved last four years and have biopharma- in the disease process. Menelas Pangalos, Ph.D., Vice President tripled the number of ceuticals and To date, approximately of Neuroscience Research at Wyeth. programs in discovery vaccines. “We $450 million has been and development,” he want to explore invested by Wyeth in says. “Programs have every option available to Alzheimer’s research – resources on a number moved from ideas in peo- us,” says Wyeth Chair- $125 million in 2006 of novel approaches to ple’s minds to agents in man and Chief Executive alone. Currently, more slow, stop or even reverse clinical testing. This has Officer Robert Essner. than 350 Wyeth the progression of the disease. Quite simply, says Dr. Pangalos, “Today, we are drawing our line in the sand for the next generation.” On that battlefront, delaying the onset or modifying the course of Alzheimer’s remains the quest. The impact of achieving this goal would be huge. According to The This series of photos represents how Wyeth is seeking to use specially engineered antibodies delivered Lewin Group, a premier to Alzheimer’s patients to stimulate an immune response that will recognize harmful plaque (in green) national health care con- and allow immune system cells (in red) to engulf the plaque and then begin to destroy it (far right). sulting firm, if therapies 17
  • 20. “My dad gave up on everything – except his music – a long time ago.” 18
  • 21. Gilbert Brown: Until the Music Stops O n Wednesdays, when activities are held at a senior day care center in Montclair, New Jersey, you might hear the strains of “Blessed Assurance,” a classic gospel song, being played. Sitting at the piano – even in the fog of Alzheimer’s – is Michael Brown’s father, Gilbert, a retired salesman who turned 80 years old in 2006 and has had Alzheimer’s disease for at least seven years. He is making music. It’s just about the only thing he can do anymore. Michael and his wife, Diane, moved his father into their home two years ago as the disease steadily pro- gressed. “My dad goes to the senior center five days a week,” Michael says. “But he doesn’t like to participate in any activities that make him think. If he can get away with it, he sits with the group that doesn’t want to do anything. But he still plays the piano – traditional gospel tunes – and some afternoons, he even plays requests. He knows about 60 songs by heart. It’s amazing.” Michael admits, though, that in every other way, his father’s Alzheimer’s disease is dispiriting. “He doesn’t know what to call common items. If you ask him a ques- tion that requires more than a yes or no, his answers are unintelligible,” Michael says. Fearing the next stages and trying to cope, both Michael and Diane attend an Alzheimer’s Association-sponsored support group for caregivers once a month at a local church. “Sometimes you get tips about how to deal with things. And sometimes when you see what others are facing, you realize that your situation isn’t as bad as it could be,” Michael says. For Michael, what hurts most is sitting across from his father. “I wish it weren’t happening, recognizing that the man my dad used to be is gone. The hardest thing is that I’ll never see him laugh or really smile again. He displays agitation, anger – or nothing,” Michael says. “Dad used to have a lot of wisdom. When you spoke with him, you usually learned something. Now he’s just in the room – that’s all.” As with so many Alzheimer’s caregivers, life has changed. “Diane and I had envisioned our lives at this stage to be quite different – taking vacations, being freer,” he adds. “But instead, we’re home by 5 p.m. every day to take care of my dad. Our lives are on hold right now. My wife is very supportive, but we’re both weary.” Gilbert Brown took piano lessons as a child, and he’s been playing the piano and organ his entire life. When Michael and Diane moved him to their home, they arranged for Gilbert’s electric organ to be shipped. “I never see him happy unless he’s playing the piano or organ,” Michael says. “My dad gave up on every- thing – except his music – a long time ago.” 19
  • 22. to delay the onset of “… if therapies to delay the onset of beta-amyloid on neurons. Alzheimer’s became Once the antibody Alzheimer’s became available available in the next five recognizes and attaches in the next five years, estimates are that years, estimates are that itself to the harmful by 2015, there would be plaques, cells in the brain by 2015, there would be 1.6 million fewer Ameri- called microglia, part 1.6 million fewer Americans with cans with Alzheimer’s, and of the body’s immune Alzheimer’s, and by 2050, by 2050, there would be system, engulf the tagged 5.3 million fewer sufferers plaques and dissolve there would be 5.3 million fewer in the United States. At the them. The monoclonal sufferers in the United States.” same time, Medicare and antibodies are delivered Medicaid – and, therefore, to patients through U.S. taxpayers – would periodic infusions, much clinical trials to modify Vaccines and save a half trillion dollars like chemotherapy treat- the disease process, all in Biologics in in health care costs. ments. The hope is that some way seeking to halt Development Ronald Black, M.D., this will slow the progres- or reduce the formation of the Neuroscience sive loss of nerve cells of harmful amyloid Clinical Development in the brain, prevent The most novel plaque deposits. group at Wyeth, notes further loss of memory approach, and some “The dis- and preserve day-to-day believe the most promis- covery that functional abilities. ing, is immunotherapy – amyloid muta- a focus of the Wyeth tions can Active Immunization and Elan alliance. Both cause rare Active immunization passive and active immu- familial cases focuses on the use of the nization approaches are of Alzheimer’s body’s own immune sys- being developed. disease led tem to clear the brain of to the develop- toxic amyloid plaques. Passive Immunization ment of ani- In this case, a vaccine AAB-001 or bap- mal models,” composed of a fragment ineuzumab, which received Ronald Black, M.D., Senior Director, Dr. Black adds. of beta-amyloid is fast track status from the Neuroscience Clinical Development at Wyeth. “These mutant injected, stimulating an U.S. Food and Drug genes have been inserted that because no one immune response in the Administration (FDA), into mice in such a way knows for certain what body and producing is Wyeth’s most advanced that the mice develop amy- causes Alzheimer’s, mul- antibodies that attach to disease-modifying therapy. loid plaques in the brain tiple paths must be taken existing plaques and It is a monoclonal anti- similar to those found in to seek treatments. “We destroy them. The first body that has been Alzheimer’s patients. These try not to be dogmatic human trial with this engineered to target toxic mice have played a critical about the cause of the potentially breakthrough beta-amyloid. Currently role in testing potential disease. Instead, we try to disease modifier, called in Phase 2 clinical trials, therapies. In fact, one of be led by the best science. AN-1792, was halted in the antibody works the reasons treatments tar- Today, the best science 2002 when a small num- by binding to amyloid- geting amyloid are more points to an important, ber of patients developed containing plaques in the advanced than other if not pivotal, role for a serious inflammation brain. In animal models, approaches has been the beta-amyloid in the pro- in the brain. this clears the amyloid ability to test these thera- gression of Alzheimer’s plaques and appears pies in animal models.” disease.” Four of Wyeth’s to neutralize some of drugs currently are in the toxic effects of 20
  • 23. completely different way on beta-amyloid. It is a novel, first-in-class and first-in-therapy approach. Symptomatic Treatments Lecozotan (SRA-333) is an oral symptomatic agent with a novel mechanism of action that modulates neurotrans- mitter pathways to improve cognitive dys- function. The robust improvement of cognitive performance in preclini- This photomicrograph of a brain section shows the neurofibrillary tangles (in black) that are characteristic of Alzheimer’s disease. These tangles develop inside nerve cells, eventually killing them. cal models highlights its potential as a next- generation symptomatic Says Dr. Pangalos, discoveries in Alzheimer’s their own so, in those therapy in Alzheimer’s “We went back to the research to enable us to cases, passive immuniza- disease. This first-in-class, lab to figure out what we begin the trials again tion may be required first-in-mechanism pro- needed to do to reduce with an improved clinical instead.” gram is in Phase 2 trials. the possibility of this side candidate.” This improved Three additional effect so that we could clinical option, ACC- Small Molecules in serotonin antagonists re-enter the clinic. What 001, currently is in Phase the Clinic are in development to we discovered was that 1 clinical trials. treat symptoms of the vaccine was stimulat- The University of Anti-amyloid Disease the disease. SAM-531, ing T cells, an immune Michigan’s Sid Gilman, Modifiers SAM-315 and SRA-444, response that causes M.D., has high hopes GSI-953 is a gamma sec- all in Phase 1, are orally inflammation in the for this strategy. “The retase inhibitor that seeks active compounds that brain. Subsequently, we immunological approach to halt toxic amyloid may enhance memory took a small fragment is the most promising production by inhibiting and reduce the cognitive of the original peptide of those we have seen so one of the two enzymatic deficits caused by used in the AN-1792 tri- far,” he says, “and active scissors important in Alzheimer’s. During als and conjugated it to immunization would the production of beta- 2007, two other agents a carrier protein like the be preferable because we amyloid protein. It is in have potential to enter one used in Prevnar, should start treatment Phase 1 trials. human trials. These are Wyeth’s pneumococcal well in advance of disease PAZ-417 is a disease- SAM-610, another sero- vaccine. We knew the onset. We would be modifying treatment tonin receptor antagonist, carrier protein was safe able to do this by actively currently in Phase 1 that and AAB-002, a mono- and thus much less likely immunizing people at seeks to slow the disease clonal antibody. to do the same thing as risk. But some elderly process and the progres- Both disease modi- AN-1792. So we used people don’t produce a sion of cognitive loss. fiers and symptomatics the technology from our good antibody response The compound is a will be important in vaccine business and to immunization on plasminogen activator combined it with our inhibitor that acts in a 21
  • 24. treating Alzheimer’s dis- “Our plan is to take as many shots 10 and 20 years from the ease. “They will make a time the initial targets on goal as possible using powerful combination,” are identified until the compounds or programs in multiple says Steve Jacobsen, first selective drugs are Ph.D., Associate Director produced,” Dr. Jacobsen areas believed to be involved in of Neuroscience says. Yet, notes Dr. the Alzheimer’s disease process … ” Research at Wyeth. “We Pangalos, “In a few cases, believe that by stopping we have gone from con- the progression of the cept to clinical trials in Researchers also are die of Alzheimer’s last year. disease, the symptomatics as little as three years. seeking to better under- And both Drs. Jacobsen we’re developing can Sometimes that has come stand the role of glucose and Pangalos lost their have more benefit about by looking at metabolism, cholesterol grandmothers to the and a longer duration advanced programs in and inflammation in disease in recent years. of action.” other therapeutic areas the disease process. “We’re not unusual,” at Wyeth and thinking And these scientists are Dr. Reinhart says. “In fact, about how we might Leaving No Stone searching for improved we’re all too common. It is apply them to the treat- Unturned models of disease to a horrible disease. You are ment of Alzheimer’s better predict efficacy forced to watch someone disease. By using models Other studies in earlier and safety in humans. you love fade away. One and insights from other stages of discovery day you realize Wyeth research areas, we include programs that that the person have reduced our time- target tau and ApoE4. you are caring lines by several years.” “Our plan is to take for is not there All agree that even as many shots on goal anymore – as advances are made in as possible using com- only his or her laboratories, progress pounds or programs appearance must be made on the in multiple areas believed remains simi- regulatory front, where to be involved in the lar. In the early the issues, in some ways, Alzheimer’s disease stages, the are unprecedented and process,” Dr. Pangalos victims clearly significant. “For exam- Peter Reinhart, Ph.D., Therapeutic Area Head says. Wyeth researchers understand ple, in short-term studies of Wyeth’s Neurodegeneration Discovery are beginning to look what is hap- Department. in patients,” Dr. Black at the possibility of pening to explains, “it may be regenerating brain cells Like so many others, them, and that can drive difficult to distinguish an lost in Alzheimer’s numerous Wyeth them into depression. It is effect on disease symp- disease, building on neu- researchers themselves as terrible as any disease toms from an effect on roregenerative research have personally wit- you can imagine. And disease progression. now under way at the nessed the devastation few understand the toll it We are exploring new Company to help stroke caused by Alzheimer’s. takes on caregivers.” ways of determining victims. Peter Reinhart, Ph.D., It’s taken a long time to the efficacy of drugs on “We are leaving no who is Therapeutic come up with potentially Alzheimer’s patients, stone unturned. We’re Area Head of Wyeth’s more effective treat- including measurement looking at ways to modu- Neurodegeneration ments. Genes involved of amyloid in the brain late a range of important Discovery Department, in Alzheimer’s first were through imaging. We target classes, including saw his grandmother identified in the mid-to- ion channels, proteases late 1980s. “It normally and kinases,” he adds. would take between 22
  • 25. “At least for now, I think she enjoys In late 2004, Violet was enrolled in a trial for an investigational drug that aims to stop the progression of a good quality of life.” the disease. Since it’s a double-blind study, Steve isn’t sure whether his mom is getting active drug or placebo. But he believes he has seen an improvement. “She’s in a Steve Szucs: Appreciating Every Day happier mood than she was two years ago though her short-term memory seems to be getting shorter. Actually, I t was Violet Szucs’ surprise 80th birthday party, and it’s pretty much nonexistent. Sometimes that’s funny. her family had gathered to celebrate. “Everyone was At other times, it’s trying.” happy,” her son Steve recalls, “with jokes all around. Today, while she spends much of her time with Steve’s But I felt something was odd about my mom. She wasn’t sister, Violet lives on her own and goes to adult day care her normal self.” five days a week – to interact with people. “That seems to Soon the changes became more apparent. “She used have made a difference in her attitude. At least for now, to call me every week. Then the calling just stopped. I think she enjoys a good quality of life,” Steve says. When the holidays came, there was no card, no gift. It But it’s a different life. “She quickly loses interest in was the first time that had ever happened,” he says. television,” Steve observes. “She’ll be laughing one minute “Finally, my mom, who always was a regular church- and then lean her head back and be sleeping the next. goer, stopped going to services. She said, ‘I just don’t feel She has a difficult time focusing. She also doesn’t remem- like it anymore.’ ” ber the year she was born. I’ll tell her it was 1923, but Six months later, in February 2004, a visit to a geriatri- 10 minutes later, she can’t remember it. She’s not what she cian confirmed Steve’s fears – Alzheimer’s disease, in the used to be at all. mild to moderate stage. Steve temporarily moved in with “Still,” he says, “right now, I’m happy for her. She’s his mom the first year after she was diagnosed. “She enjoying every day as much as she can. And my daughter seemed confused and disorganized, and she couldn’t take will know her grandmother. I know it won’t always care of the house the way she always had,” he recalls. be like this so I appreciate the time we have together.” 23
  • 26. “We don’t expect our parents to go through this. They are the people who used to make sure the world was okay for us …”
  • 27. Ana Alvarado: Taking Care of Mom A na Alvarado is 48 years old. She has her work – as a Spanish teacher – and she has her mom – Antonia, age 77, who suffers from Alzheimer’s disease. “My mom lives with my brother and me,” Ana says. “Taking care of her is a 24/7 task. I have to get up at 4 a.m. to go to work so I have a homemaker come to our house in the mornings. Later, an aide stays with my mom until my brother gets home from work.” Ana’s sister lives up the street, and, in between jobs, she stops in to make sure everything is okay. Antonia was diagnosed three years ago after exhibiting sudden changes in behavior. “You would talk with her, and she’d always make excuses for not doing something. That was very unlike her,” Ana reports. “And when our family would get together, she’d get upset because other people were around, and she felt she wasn’t getting enough attention.” Today, even as some of those symptoms have abated, Antonia’s memory loss has advanced. “She knows I’m a familiar face, but now and then she’ll ask, ‘Where’s Ana?’ She’ll talk about events and people from her earliest years, but she doesn’t remember my father, who died 15 years ago, and she doesn’t know what day it is,” Ana says. “I’ve seen her get worse. The mood swings vary from day to day.” And other behaviors have emerged. “When we go out in public, she wants to physically embrace people in the stores, and she thinks everyone understands Spanish,” Ana notes. “Mom used to speak English but doesn’t anymore, and she watches soap operas but doesn’t know what’s going on.” Dealing with this has been painful. “I was angry at the beginning, having a mother but not having a mother,” Ana says. “I had to deal with the fact that I no longer could rely on her as a parent.” Then there are the hardships of caregiving. “At the extreme, I suppose she could go into a nursing home,” Ana adds. “But I don’t want her to do that. I’m Spanish, and we care for our elders. To keep my sanity, I turn a lot of my attention to work.” Antonia once had another life. “My mom always was a pleasant woman. She was a seamstress and was very independent. And she took care of the world,” Ana says. “She was well-dressed, and her makeup was just right. But today, even bathing her is a challenge. “We don’t expect our parents to go through this. They are the people who used to make sure the world was okay for us,” Ana adds. “But she’s my child now – and sometimes not an easy child.” 25
  • 28. “We expect to see failures, but Susan Kundel, Vice President for Neuro- we also anticipate that science New Business at within a relatively short period Wyeth, says, “This is a universally dreaded of time, we will have a disease. And now we clear ability to modify the course have within our grasp the of this disease.” possibility of doing some- thing about it. We are on the leading edge of sci- where we can make sig- Alzheimer’s is a death ence, and that means nificant change in the sentence,” says Dr. Black. there are many uncertain- outcome, along the lines “Similar to cancer patients ties and unknowns. We of the improvements we and their families, they expect to see failures, but saw in cancer and HIV in want effective therapies we also anticipate that Steve Jacobsen, Ph.D., Associate Director of the last decade. If we can to combat the disease and within a relatively short Neuroscience Research show that a drug truly is are willing to accept the period of time, we will at Wyeth. slowing the progression risks that may go along have a clear ability to of a terminal illness, then with these medications. modify the course of this still will examine mem- a higher level of risk may The Alzheimer’s patients disease. The price for ory and quality of life be acceptable. We have and their families who working in this disease is when we evaluate our heard from patients and participate in our clinical uncertainty. But what disease-modifying thera- caregivers over and over trials are our biggest you get in return is a lot pies, but we hope these again that they know allies in this effort.” of hope.” new endpoints will help us get our drugs to patients sooner. If these images show us that our drugs are reducing the amount of amyloid in the brain or are slowing the loss of neurons, it will be important evidence that our drugs are imped- ing the progression of the disease. Will every- one, including regulators, agree that these are proper endpoints?” The discussions continue. As more effective therapies enter clinical trials, Dr. Black believes that attitudes will change. “We should be thinking about Alzheimer’s as a disease In Alzheimer's disease, the cerebral cortex of the brain, shown in this PET scan, is atrophied due to the death of many neurons, and metabolic activity (shown in red) is decreased, leading to cognitive and behavioral dysfunction. 26
  • 29. The Path Forward Forging Partnerships for Progress aby boomers “Our aim is to foster a sense one – a spouse, a parent, B fear Alzheimer’s an aunt, an uncle – who of national urgency disease and the has fallen prey to this about Alzheimer’s disease.” shadow it already is disease,” he told a 2005 casting on the lives of White House Conference people as they age – and on Aging. “A recent on the lives of those Gallup poll found that who care for them. nearly 50 percent of those A survey conducted by responding worry about ACT-AD (Accelerate Cure/ developing Alzheimer’s Treatments for Alzheimer’s disease. However, instead Disease), a recently formed of spurring people into coalition of close to 50 action, this knowledge leading advocacy groups, seems to engender a asked more than 1,000 sense of resignation, of Americans born between inevitability. What we lack 1946 and 1964 about the is a worldwide clamor for disease. immediate action and a solution. I know of no dis- ease in our country where Unprepared for a more patients are waiting Health Care Crisis with so much need and so little hope. It does not Less than 10 percent have to be so.” think current treatments ACT-AD represents Alzheimer’s disease, there Today, in addition for the disease are ade- patients, caregivers, con- was a visceral reaction to its wide-ranging quate. Nearly all say they sumers, older Americans, and an awakening to the research and development would be unprepared or researchers and women’s reality of what could efforts to find better would find life not worth health advocates. It was await them.” and more effective treat- living if they were forced organized in April 2006 Wyeth believes that ments, Wyeth is hard at to face the limitations and received initial patients, industry and work partnering with common to the disease. support through an edu- government must partner patient groups, talking And about 80 percent say cational grant from to help accelerate research with regulators in both the their current savings Wyeth and Elan Corpora- for therapies that halt or United States and interna- would not cover the cost tion. “Many boomers reverse the progression of tionally, and, in essence, of care. Overwhelmingly, currently are focused on Alzheimer’s disease. leaving no stone unturned they express concern other health issues and across many complex about the government’s mistakenly consider The Need for a and difficult battlefronts. ability or even willing- Alzheimer’s a problem of Greater Focus on “Our aim is to ness to address this their elders,” says Daniel foster a sense of national Alzheimer’s looming personal and Perry, Executive Director urgency about Alzheimer’s public health care crisis. of the Alliance for Aging disease,” says Jill Arent, Wyeth Chairman and Wyeth and other Research and Chair Senior Director, Federal CEO Robert Essner groups are making a con- of ACT-AD. “But when Health Policy in Wyeth’s emphasizes the need to act certed effort to help asked to consider them- Public Policy group.“The now – on many fronts – address those fears and to selves at age 70 with successful mechanisms to better mobilize society’s change the landscape of that the U.S. Food and war on Alzheimer’s. treatment and care. “We’ve all known some- 27
  • 30. Drug Administration “We need to develop a dollars.” Currently, (FDA) already has 50 percent of nursing road map that would lay out developed to address the home admissions are due a comprehensive approach urgent need for new to Alzheimer’s disease or AIDS and cancer thera- related disorders. to dealing with the societal costs pies can and should of this devastating illness.” be applied to innovative Demonstrating treatments for the Power of Alzheimer’s disease.” the Human Spirit and applied research A Disease of Speaking at a forum, tracks to outline the Two Victims: Patient “Preparing the Country for The Alzheimer’s Founda- biggest breakthroughs and Caregiver the Alzheimer’s Epidemic,” tion of America (AFA) is still required and deter- Newt Gingrich, Center for one of the founding mining ways to resource Health Transformation Ultimately, Joel Ross, groups of ACT-AD and their development; founder, agreed: “We need M.D., a practicing represents numerous creating an FDA model to develop a road map geriatrician, recognizes organizations around the of operations for the that would lay out a what those involved in the country that focus on brain sciences that cuts comprehensive approach disease know too well. serving and advocating across existing systems to dealing with the Caregiving at home still for patients and their to address the realities of societal costs of this dev- comprises more than caregivers. “What is awe an emerging science; and astating illness. I hope 70 percent of all inspiring is the length and developing optimum this will lead to a con- Alzheimer’s disease care. breadth to which a care- public policies to support gressional hearing and “It is a disease of two giver will go – in the name caregivers. concerted measures by victims: the patient and of love – to provide for a Sid Gilman, M.D., the legislative and execu- the caregiver,” he says. spouse, parent or other of the University of tive branches. Legislators “One dies from or with relative. It says something Michigan, wants a fresh need to be mobilized the disease, and one is about the human spirit,” look at the risk/benefit for Alzheimer’s the way permanently damaged – says Eric J. Hall, Chief ratio. “We need to view they have been for forever scarred by it. Executive Officer of AFA. Alzheimer’s disease AIDS and avian flu.” For years at a time, home “What can we do to help as equivalent to cancer. caregivers work hard the increasing number We need to streamline the Outlining a Plan to cope and deal with of caregivers and their review process for med- Alzheimer’s, yet they try for the Future loved ones with dementia? ication approval as we to remain hopeful and AFA has hundreds of did for cancer therapies, optimistic. Right now, the A former Speaker of organizations across meaning we need to government pays little the U.S. House of Repre- the country that support accept higher levels of or nothing for at-home or sentatives, Mr. Gingrich caregivers and individuals risk. Our medical systems day care for sufferers described specific with dementia who no have not acknowledged but pays heavily for insti- elements for the path longer can speak for them- as yet the full impact of tutional care. If the forward: maximizing selves. AFA gives them a this disease – its severity, government helped home the evolution of imaging united voice, and it gives its consequences, its caregivers pay for the capabilities for inexpen- them hope. The caregivers costs, its horrors.” needed services, then sive and routine early and sufferers desperately nursing home admissions diagnosis; designing basic need champions.” might be avoided or at least delayed, saving the government billions of 28
  • 31. “… there are no magic bullets. But But now he sees considerable memory loss. They have two children, but she can’t remember their names. just give up? I wouldn’t do that.” “Sometimes, however, she still calls me Dick. It’s been awhile since she could read. And she requires assistance with all the functions of daily living,” he says. When Dick Cone: Bringing Dignity to a Disease Dick leaves the house to do volunteer work or to run errands, someone comes in to help. He’s also spent a D ick Cone finds strength through his faith. It has great deal of time remodeling their house to accommo- helped him remain resolute in his determination to date Phyllis’ needs. “Since I like to cook, I expanded keep his wife, Phyllis, at home with him as long as the kitchen so she can be right there with me.” He he can. “A nursing home for my wife? That’s not going admits it’s tough, though. “There’s not a lot of support to happen if I can help it,” he says emphatically. with Alzheimer’s,” he adds. “And there are no magic Phyllis is 77 years old – his age. They’ve been married bullets. But just give up? I wouldn’t do that. 56 years and live in St. Louis, Missouri. It was clear “I know I’ve lost a lot of her,” Dick continues. “The something was wrong with her about 10 years ago. physical relationship is gone. The memories we used “I first noticed it when she failed to remember a major to share are gone. While she can’t have a conversation, construction project we had undertaken,” Dick recalls. I know she’s aware – she responds, she still is here with “When we talked about it, all she could say was, me.” He often invites family and close friends to visit. ‘What project?’ ” A definitive Alzheimer’s diagnosis “Phyllis enjoys being here at home, at the table sur- came in 2002. rounded by others,” he says. “She’s part of the picture. Dick’s perseverance led to finding medications that It’s a comfort being in this house. This is the window “helped push the clock back about two years or so through which we view the world. This is our yard. for her,” he notes, as she found herself unable to partici- These are our flowers. There is a quality of life here. pate in activities she once had enjoyed – music, church There is family here. My prayer is to help me be strong groups, cultural organizations. enough to keep on going … for her.” 29
  • 32. What the Future Holds Where do we hope to be 10 years from now? he power of this answers to crossword T “ disease and the puzzles in ink and he was challenge of con- a long-distance runner. quering it drives us on,” But all those activities Wyeth Chairman and didn’t make a difference.” CEO Robert Essner has She adds, “I saw said. “What we need is a what happened to my sense of urgency analo- husband during a brief gous to that which arose institutional stay, and it around AIDS. In the war made me physically ill. So against AIDS, govern- I elected to do whatever ment, regulatory agencies, was necessary to keep scientists in industry and Harvey from having to academia, and patient leave home for his care. groups worked hand in We still may go bankrupt “We need to reshape the debate hand to develop new after all these years of therapies and to evaluate medical expenses, but I and dialogue around Alzheimer’s. them as rapidly as possi- will have no regrets.” People need to understand the ble. The results were John Dwyer is a neurological holocaust remarkable.” Washington, D.C., In addition to its attorney, health care that Alzheimer’s disease represents wide-ranging research entrepreneur and for society.” and development efforts Alzheimer’s disease advo- to find better and more cate. “We need to reshape effective treatments, the debate and dialogue Wyeth is hard at work around Alzheimer’s,” for the future and how sometimes with help but partnering with patient he says. “People need to best to get new drugs and more often alone – and groups and talking with understand the neurologi- more hope to patients to be on the frontlines as regulators in both the cal holocaust that sooner. an advocate for other United States and interna- Alzheimer’s disease repre- Meryl Comer, pictured patients and caregivers. tionally. The Company is sents for society. But, on page 13 of this report, Meryl is upset about leaving no stone unturned at the same time, we can’t believes that Alzheimer’s how Alzheimer’s is seen across many battlefronts. afford a long slog for disease “should be the by others. “Alzheimer’s Breakthroughs will new treatments. If we baby boomer’s worst too often is portrayed as require the best that want to give hope to nightmare.” It certainly a benign disease of aging. science can offer as more people, the short answer has been for her and her But my husband main- potential advances than is that we need to develop husband, Dr. Harvey tained his mind and his ever appear in the lab a strategic national plan Gralnick, who has suf- body all his life. He had or on the horizon. It will against Alzheimer’s fered with the disease more than 200 research require society taking a disease, and we need to for more than a decade. papers published, he fresh look in the mirror – energize and mobilize Meryl gave up a successful was fluent in three as we age and as our the 50- and 60-year-olds career in broadcast jour- languages, he filled in parents age – to deter- who are at risk – and nalism in Washington, mine the right road map that may be all of us.” D.C., to devote herself to his 24-hour care – 30
  • 33. “I try to offer as much support Doris’ dementia seemed to accelerate. “She didn’t realize she had broken her hip and didn’t know enough to try to as I can, to tell my stories and to get better physically so I could take her home,” he says. “It was bad. She kept falling because she didn’t know she share my experiences.” couldn’t walk.” But through this self-described nightmare, Billings continued to care for her. “I had my own business, but I Billings Fuess, Jr.: Saying Goodbye finally had to dissolve that.” He also started going to a support group. “I found the sessions helpful. It’s tough O ver the past 10 years, as his wife, Doris, deteriorated to deal with this alone. There’s so much heartbreak.” from Alzheimer’s disease, Billings Fuess, Jr., suffered Wanting to help others, Billings still attends the group. alongside her, learning more about loss than he ever “I try to offer as much support as I can, to tell my stories thought possible. “You lose the one you love bit by bit,” and to share my experiences.” the New Jersey resident and retired advertising copy- On January 7, 2006, Billings and his wife exchanged writer recalls. “She was slowly sinking below the water’s wedding bands in the rehabilitation facility. “We were surface, and I couldn’t pull her up. married in 1952, but we didn’t have a double ring cere- “In the mid-1990s, I began to suspect something was mony back then,” he says. “On that special day last year, wrong with her mind,” Billings adds. “Over time, Doris we slipped on our rings and it was all very happy.” The couldn’t read from one line to the next and couldn’t focus next day, with her family at her side, she passed away. on anything. She would get frustrated when watching “When Doris was well,” he says, “our grandchildren movies because she couldn’t understand all the twists and were her great joy. She also worked in the bridal registry turns. And she had trouble reading mystery stories for of a department store and liked to read, visit friends much the same reason. But she never forgot who I was.” and go antiquing. She touched a lot of people along the He believes that after a hip operation two years ago way. I miss her dreadfully.” and a stay in the hospital and rehabilitation facility, 31
  • 34. Selected Products from Wyeth Wyeth Pharmaceuticals Wyeth Consumer Fort Dodge Healthcare Animal Health Cardiovascular and Nutritionals Analgesics Bronchi-Shield Gastrointestinal Bursine Nursoy Advil CYDECTIN Inderal LA Progress Advil PM Duramune Protonix Progress Gold Anadin Fel-O-Vax/Pentofel Protonix I.V. Promil Children’s Advil Fluvac Innovator/Duvaxyn Zoton Promil Gold Robaxin LymeVax Promise Spalt Nolvasan Promise Gold Hemophilia Polyflex S-26 Cough/Cold/Allergy BeneFIX Poulvac S-26 Gold ReFacto Advil Cold & Sinus ProHeart/Guardian Alavert ProMeris Vaccines Children’s Advil Cold Immunology Pyramid Meningitec Dimetapp and Oncology Quest/Equest Prevnar/Prevenar Robitussin Mylotarg Rabvac Neumega Suvaxyn Women’s Health Care Nutritional Supplements Rapamune Synovex Alesse/Loette Caltrate Telazol Lo/Ovral Centrum Infectious Disease ToDAY Minesse Centrum Select ToMORROW Tygacil Premarin Centrum Silver Torbugesic/Torbutrol Zosyn/Tazocin Premarin Vaginal Cream Polase Triangle Premphase Vitasprint B12 West Nile-Innovator Inflammatory Disease Prempro/Premelle Enbrel* Totelle Other Products Triphasil/Trinordiol Anbesol Neuroscience ChapStick Effexor/Efexor FiberCon Effexor XR Preparation H Primatene * Co-promoted with Amgen Inc. The above products are identified as trademarks used by Wyeth and its subsidiaries. 32
  • 35. Directors and Officers Board of Directors Principal Corporate Officers Principal Division and Subsidiary Officers Fort Dodge Animal Robert Essner 1 Robert Essner 7,8,9,10,11 Paul J. Jones 8,9 Health Chairman and Chief Chairman and Vice President Executive Officer Chief Executive Officer and Controller E. Thomas Corcoran 7,9,10 President John D. Feerick Bernard Poussot Jeffrey E. Keisling 2,5 7,8,9,10,11 Wyeth Consumer Professor of Law, President, Chief Operating Vice President – Corporate Healthcare Fordham University Officer and Vice Chairman Information Services and Douglas A. Rogers 7,8,9,10 School of Law Chief Information Officer Kenneth J. Martin 7,8,9,10,11 President Frances D. Fergusson, John C. Kelly Chief Financial Officer and Wyeth Consumer Ph.D. 4,5,6 Vice Chairman Vice President – Healthcare – Finance Operations President Emeritus Thomas Hofstaetter, International Vassar College Eileen M. Lach 8 Ph.D. 7,9 Etienne N. Attar 9 Victor F. Ganzi 2,3,12 Vice President, Corporate Senior Vice President – President Secretary and Associate President and Chief Corporate Business General Counsel Wyeth Executive Officer, Development The Hearst Corporation Pharmaceuticals – David A. Manspeizer 8 René R. Lewin 7,8,9,10,11 Global Business Robert Langer, Sc.D. 4,5,6 Vice President – Intellectual Senior Vice President – Joseph M. Mahady 7,8,9,10 Property and Associate Institute Professor, Human Resources President General Counsel Massachusetts Institute Joseph M. Mahady 7,8,9,10 of Technology Wyeth James J. Pohlman Senior Vice President Pharmaceuticals – John P. Mascotte 1,2,3,5,12 Vice President – Corporate Marily H. Rhudy 7,9 Asia/Pacific and Strategic Initiatives Retired President and Senior Vice President – Nutritionals Chief Executive Officer, Steven A. Tasher 8 Public Affairs Mark M. Larsen 9 Blue Cross and Blue Shield Vice President – President of Kansas City, Inc. Robert R. Environmental Affairs and Ruffolo, Jr., Ph.D. 7,8,9,10 Wyeth Raymond J. McGuire Facilities Operations and Senior Vice President Associate General Counsel Pharmaceuticals – Managing Director, Co-Head, Global Investment EMEA/Canada Lawrence V. Stein 7,8,9,10,11 Justin R. Victoria Banking, Citigroup Global Ulf Wiinberg 7,9 Senior Vice President and Vice President – Markets Inc. President General Counsel Investor Relations Mary Lake Polan, Wyeth Ulf Wiinberg 7,9 Robert E. Landry, Jr. 11 M.D., Ph.D., M.P.H. 4,5,6 Pharmaceuticals – Senior Vice President Treasurer Professor and Chairman Latin America Mary Katherine Wold 10,11 Emeritus, Department of Eduardo G. Nieto 9 Senior Vice President – Obstetrics and Gynecology, President Tax and Treasury Stanford University School Wyeth of Medicine Douglas A. Dworkin 8 Pharmaceuticals – Vice President and Bernard Poussot Technical Operations Deputy General Counsel President, Chief Operating and Product Supply Officer and Vice Chairman Leo C. Jardot Charles A. Portwood 7,8 Vice President – President Gary L. Rogers 2,3 Government Relations Former Vice Chairman, Wyeth General Electric Company Pharmaceuticals – United States and Ivan G. Seidenberg 1,3,4 Wyeth Pharmaceutical Chairman and Chief Business Unit Executive Officer, Verizon Geno J. Germano 9 Communications Inc. President and General Walter V. Shipley 3,5 Manager Retired Chairman of Wyeth Research the Board, The Chase 8 Law/Regulatory Review 1 Executive Committee Robert R. Ruffolo, Jr., Manhattan Corporation Committee 2 Audit Committee Ph.D. 7,8,9,10 9 Operations Committee 3 Compensation and Benefits John R. Torell III 2,4 President 10 Human Resources and Committee Partner Benefits Committee 4 Corporate Issues Committee Core Capital Group 11 Retirement Committee 5 Nominating and Governance 12 Designated to be a “Financial Committee Expert” as defined in 6 Science and Technology Committee applicable SEC rules 7 Management Committee 33
  • 36. Selected Financial Data (Dollar amounts in thousands except per share amounts) Year Ended December 31, 2006 2005 2004 2003 Net revenue $18,755,790 $17,358,028 $15,850,632 $ 20,350,655 Research and development expenses 2,749,390 2,460,610 2,093,533 3,109,060 Net income 3,656,298 1,233,997 2,051,192 4,196,706 Diluted earnings per share 2.70 0.91 1.54 3.08 Dividends per common share 0.9400 0.9200 0.9200 1.01 Capital expenditures 1,081,291 1,255,275 1,908,661 1,289,784 Total assets $35,841,126 $33,629,704 $31,031,922 $ 36,478,715 Number of common stockholders 50,648 54,301 59,181 47,314 Number of employees at year end 49,732 51,401 52,385 50,060 Wages and salaries $ 3,434,476 $ 3,280,328 $ 3,003,555 $ 3,488,510 Company Data by Reportable Segment (In millions) Year Ended December 31, 2006 2005 2004 2003 Net Revenue from Customers Pharmaceuticals $15,321.1 $13,964.1 $12,622.7 $16,884.2 Consumer Healthcare 2,553.9 2,557.4 2,434.5 2,530.2 Animal Health 880.8 836.5 793.4 936.3 Consolidated total $18,755.8 $17,358.0 $15,850.6 $20,350.7 Income (Loss) before Income Taxes Pharmaceuticals $ 4,544.9 $ 4,040.1 $ 3,798.5 $ 5,186.4 Consumer Healthcare 574.3 578.6 592.4 516.2 Animal Health 139.4 134.8 127.4 163.7 Corporate (478.0) (4,883.3) (2,156.7) (436.4) Consolidated total $ 4,780.6 $ (129.8) $ 2,361.6 $ 5,429.9 Depreciation and Amortization Expense Pharmaceuticals $ 682.0 $ 529.5 $ 458.0 $ 719.9 Consumer Healthcare 40.8 45.7 34.9 20.0 Animal Health 30.3 29.9 25.9 32.7 Corporate 33.8 17.3 19.1 30.4 Consolidated total $ 786.9 $ 622.4 $ 537.9 $ 803.0 Expenditures for Long-Lived Assets Pharmaceuticals $ 1,077.9 $ 1,226.5 $ 1,742.1 $ 1,228.3 Consumer Healthcare 28.4 33.2 53.8 35.3 Animal Health 45.0 40.0 28.4 37.2 Corporate 47.1 83.4 126.3 72.0 Consolidated total $ 1,198.4 $ 1,383.1 $ 1,950.6 $ 1,372.8 Total Assets at December 31, Pharmaceuticals $15,770.2 $15,771.2 $14,513.7 $ 17,171.6 Consumer Healthcare 1,463.2 1,701.4 1,742.8 1,492.9 Animal Health 1,326.7 1,340.9 1,328.4 1,430.0 Corporate 17,281.0 14,816.2 13,447.0 16,384.2 Consolidated total $35,841.1 $33,629.7 $31,031.9 $36,478.7 34
  • 37. Worldwide Net Revenue by Product (In millions) 2006 2005 2004 2003 Pharmaceuticals Effexor $ 3,458.8 $ 3,347.4 $ 2,711.7 $ 3,722.1 Prevnar 1,508.3 1,053.6 945.6 1,961.3 Protonix 1,684.9 1,590.6 1,493.3 1,795.0 Enbrel 1,083.7 680.0 298.9 1,499.6 Nutrition 1,040.9 943.3 857.6 1,200.8 Premarin family 908.9 880.2 1,275.3 1,050.9 Zosyn/Tazocin 891.6 760.3 638.7 972.0 Oral contraceptives 525.3 590.1 589.2 454.9 BeneFIX 343.3 301.5 248.1 357.6 Rapamune 300.2 259.0 169.8 336.9 rhBMP-2 236.3 165.3 58.1 308.0 ReFacto 268.4 249.4 224.2 305.6 Zoton 375.7 447.7 363.2 130.8 Tygacil 10.0 — — 71.5 Alliance revenue 1,146.5 789.9 654.4 1,339.2 Other 1,537.7 1,708.3 1,872.0 1,378.0 Total Pharmaceuticals $15,321.1 $13,964.1 $12,622.7 $16,884.2 Consumer Healthcare Centrum $ 634.0 $ 616.6 $ 545.6 $ 657.1 Advil 514.0 490.4 450.9 620.2 Robitussin 253.2 237.9 230.3 225.5 Caltrate 189.2 179.0 153.4 195.1 ChapStick 134.4 123.2 113.9 127.9 Preparation H 104.8 102.3 92.3 103.1 Dimetapp 80.4 87.8 85.2 81.7 Alavert 49.5 56.0 81.6 49.8 Advil Cold & Sinus 122.4 129.7 134.7 61.0 Solgar 58.5 105.5 105.1 — Other 413.5 429.0 441.5 408.8 Total Consumer Healthcare $ 2,553.9 $ 2,557.4 $ 2,434.5 $ 2,530.2 Animal Health Livestock products $ 377.2 $ 351.0 $ 329.2 $ 405.5 Companion animal products 257.8 252.6 226.7 283.9 Equine products 138.2 138.2 147.2 135.5 Poultry products 107.6 94.7 90.3 111.4 Total Animal Health $ 880.8 $ 836.5 $ 793.4 $ 936.3 35
  • 38. Corporate Data Executive Offices BuyDIRECT Stock Purchase and Corporate Citizenship Sale Plan Wyeth Corporate Citizenship 2006 – Living Five Giralda Farms Our Values, a report describing the The BuyDIRECT plan provides stock- Madison, NJ 07940 Company’s efforts in the areas holders of record and new investors with (973) 660-5000 of governance, employee development, a convenient way to make cash pur- support for our communities, and chases of the Company’s common stock www.wyeth.com protection of the environment and the and to automatically reinvest dividends. health and safety of our employees, Inquiries should be directed to The Bank is available on the Web at of New York. Stock Trading Information http://www.wyeth.com/aboutwyeth/ Wyeth stock is listed on the New York citizenship or via written request to: Reports Available Stock Exchange (ticker symbol: WYE). Wyeth A copy of the Company’s 2006 Annual Public Affairs Report on Form 10-K may be obtained Five Giralda Farms Independent Registered Public by any stockholder without charge Madison, NJ 07940 Accounting Firm through The Bank of New York. Addi- PricewaterhouseCoopers LLP tionally, this report and all Company Trademarks 400 Campus Drive filings with the Securities and Exchange Florham Park, NJ 07932 Product designations appearing in Commission can be accessed on our differentiated type are trademarks. Web site at www.wyeth.com. Trademarks for products that have not Annual Meeting received final regulatory approval are The Annual Meeting of Stockholders Equal Employment Opportunity subject to change. will be held on Thursday, April 26, 2007 Our established affirmative action and at the Hyatt Morristown in Morristown, equal employment programs demon- Cautionary Statement New Jersey. strate our long-standing commitment to The information in this Annual Review is provide job and promotional opportu- a summary and does not provide com- nities for all qualified persons regardless Stockholder Account Information plete information; it should be considered of age, color, disability, national origin, The Bank of New York is the transfer along with the information contained in race, religion, sex, sexual orientation, agent, registrar, dividend disbursing the Company’s 2006 Financial Report, status as a Vietnam-era veteran or a agent and dividend reinvestment agent 2006 Annual Report on Form 10-K and special disabled veteran, or any military for the Company. Stockholders of record other periodic filings with the Securities uniformed services obligation. with questions about lost certificates, and Exchange Commission. lost or missing dividend checks, or This Annual Review includes for- notification of change of address should Environment, Health and Safety ward-looking statements reflecting the contact: Information on the Company’s Company’s current views at the time The Bank of New York environmental, health and safety these statements were made with respect P.O. Box 11002 (EHS) performance and its EHS to future events and financial perfor- Church Street Station Policy is available on the Web at mance. All forward-looking statements Design: Arnold Saks Associates Major Photography: Mark Tuschman Text: Max J. Friedman New York, NY 10286 http://www.wyeth.com/aboutwyeth/ address matters involving numerous citizenship/ehs. EHS information assumptions, risks and uncertainties, (800) 565-2067 also is included in Corporate which may cause actual results to differ (Inside the United States and Canada) Citizenship 2006 – Living Our Values, materially from those expressed or (212) 815-3700 which is available on the Web at implied by the Company in those state- (Outside the United States and Canada) http://www.wyeth.com/aboutwyeth/ ments. In particular, the Company For the hearing impaired: citizenship. The EHS Policy also may encourages the reader to review the risks (888) 269-5221 (TDD) be obtained upon written request to: and uncertainties described under the Wyeth heading “Item 1A. RISK FACTORS” E-mail: shareowners@bankofny.com Department of Environment, in the Company’s 2006 Annual Report Internet address: www.stockbny.com Health and Safety on Form 10-K. Accordingly, the Com- Five Giralda Farms pany cautions the reader not to place Madison, NJ 07940 undue reliance on these forward-looking statements, which speak only as of the date on which they were made. 36
  • 39. Mission & Vision Values Mission To achieve our mission and realize our vision, we must live by our values: We bring to the world pharmaceutical and health care products that improve Quality lives and deliver outstanding value to our customers and shareholders. We are committed to excellence – in the results we achieve and in how Vision we achieve them. Our vision is to lead the way to a healthier Integrity world. By carrying out this vision at We do what is right for our customers, every level of our organization, we will be our communities, our shareholders recognized by our employees, customers and ourselves. and shareholders as the best pharmaceutical company in the world, resulting in value Respect for People for all. We promote a diverse culture and a commitment to mutually respect We will achieve this by: our employees, our customers and • Leading the world in innovation our communities. through pharmaceutical, biotech and Leadership vaccine technologies • Making trust, quality, integrity and We value people at every level who lead excellence hallmarks of the way we by example, take pride in what they do do business and inspire others. • Attracting, developing and motivating Collaboration – “Teamwork” our people We value teamwork – working together • Continually growing and improving to achieve common goals is the our business foundation of our success. • Demonstrating efficiency in how we use resources and make decisions
  • 40. Five Giralda Farms Madison, NJ 07940