wyeth 2006 Annual Review


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wyeth 2006 Annual Review

  1. 1. Leading the Way to a Healthier Annual Review 2006 World
  2. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 15. “Good morning, love. My name is Meryl. I am your wife …” 13
  16. 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. 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. 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