/FIRST ADD -- NYW043A -- Pfizer Inc Fourth-Quarter 2004 Performance Report/

/FIRST ADD -- NYW043A -- Pfizer Inc Fourth-Quarter 2004 Performance Report/ PFIZER INC SUPPLEMENTAL INFORMATION SHARES OUTSTANDING AND EPS INFORMATION: FY04 FY03 Shares Outstanding (millions) - Basic EPS 7,530.6 7,212.8 Basic EPS $1.51 $.54 Adjusted Basic EPS* $2.14 $1.71 Shares Outstanding (millions) - Diluted EPS 7,613.9 7,285.6 Diluted EPS $1.49 $.54 Adjusted Diluted EPS* $2.12 $1.69 4Q04 4Q03 Shares Outstanding (millions) - Basic EPS 7,461.2 7,585.6 Basic EPS $.38 $.08 Adjusted Basic EPS* $.58 $.51 Shares Outstanding (millions) - Diluted EPS 7,510.6 7,668.3 Diluted EPS $.38 $.08 Adjusted Diluted EPS* $.58 $.50 * "Adjusted income," "adjusted basic earnings per share (EPS)," and "adjusted diluted EPS" are defined as reported net income, reported basic EPS, and reported diluted EPS excluding discontinued operations, the cumulative effect of a change in accounting principle, significant impacts of purchase accounting for acquisitions, merger-related costs, and certain significant items. A reconciliation to reported net income and reported diluted EPS is provided within this document. QUESTIONS: PRODUCT PERFORMANCE / NEW PRODUCT DEVELOPMENT CARDIOVASCULAR / METABOLIC / ENDOCRINE Q1) How is Lipitor performing? A1) Worldwide sales of Lipitor totaled $3.264 billion in the fourth quarter of 2004, reflecting growth of 23% compared to the same period in 2003. It is the best-selling pharmaceutical product of any kind in the world and the industry's first $10 billion product. Lipitor continued to achieve double-digit unit growth worldwide. In the U.S., November represented Lipitor's strongest month of performance in two years, with new-prescription growth of 23% (versus 27% market growth and 25% statin growth) and total- prescription growth of 16%. This impressive performance can be attributed to ground-breaking clinical data, more aggressive treatment guidelines, and increased promotion within the category. Lipitor has a growing body of evidence demonstrating benefit to patients by impacting disease progression and by reducing heart attacks and strokes (the ASCOT, CARDS, REVERSAL, PROVE-IT, and ALLIANCE clinical trials). The safety profile and efficacy of Lipitor have been demonstrated in more than 400 ongoing and completed clinical trials involving more than 80,000 patients and in more than 87 million patient years of therapy. These results further support the outstanding record of Lipitor in cholesterol reduction, proven cardiovascular (CV) outcomes benefit, and patient safety across the full dosing range. Two studies involving Lipitor were stopped early due to the benefits seen in reducing CV outcomes. The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) showed that people with hypertension and normal to mildly elevated cholesterol levels without a history of coronary heart disease had 36% fewer fatal coronary events and non-fatal heart attacks, 27% fewer fatal and non-fatal strokes, and 21% fewer cardiovascular events and procedures when taking Lipitor than patients treated with placebo. The CARDS study, which was presented at the American Diabetes Association meeting in 2004, showed that treatment with Lipitor provided early and significant benefits in prevention of coronary heart disease (37% reduction) and stroke (48% reduction) in patients with diabetes and relatively low LDL-cholesterol levels (median: 118 mg/dL). Exploring atherosclerosis progression, REVERSing Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) is a major comparative trial comparing the benefits of Lipitor 80 mg versus Pravachol 40 mg. Results from this trial were published in The Journal of the American Medical Association in March 2004. In REVERSAL, Lipitor halted the progression of atherosclerosis compared to Pravachol, which only slowed the progression of disease. In addition, Lipitor demonstrated a greater impact on atherosclerosis progression even when the same LDL-cholesterol percentage reductions were achieved compared to Pravachol. The PROVE-IT trial, sponsored by Bristol-Myers Squibb, evaluated the same treatment regimen as in REVERSAL on cardiovascular morbidity and mortality in patients with acute coronary syndrome. The results of this study showed that patients treated with Lipitor 80 mg demonstrated early and significant protection against death and major cardiovascular endpoints versus less intensive treatment with Pravachol 40 mg. As in REVERSAL, the safety profiles of Lipitor 80 mg and Pravachol 40 mg were comparable. The results of PROVE-IT were published in The New England Journal of Medicine. The outcomes data from PROVE-IT complement the results from the REVERSAL trial. Most recently, the January 6, 2005, issue of The New England Journal of Medicine included the publication of a post-hoc analysis of the REVERSAL trial and a pre-specified analysis of the PROVE-IT trial. These analyses examine the effects of statin therapy and the roles of LDL cholesterol and C-reactive protein (CRP) in disease progression and CV outcomes. The results also provide the first evidence to show that reductions in CRP may have clinical importance. This evidence suggests that CV benefits of LIPITOR may not be completely explained by aggressive LDL-cholesterol lowering alone and that other mechanisms may also play a role. In REVERSAL and PROVE-IT, greater reductions in CRP with Lipitor seem to translate into slower disease progression and reduced CV events. Further research is ongoing to explore vasculoprotective effects of Lipitor beyond the benefit from aggressive LDL-cholesterol lowering. There continues to be an opportunity for further growth of the cholesterol-lowering market. Of the tens of millions of individuals around the world that are in need of medical therapy for high cholesterol, only about one third are actually receiving treatment. Worldwide, millions of people with high cholesterol are not diagnosed, are not treated, or are treated with a dose inadequate to achieve their cholesterol goals. Evolving treatment guidelines continue to encourage the broad use of statin therapy. Q2) How is Caduet performing? A2) Worldwide sales of Caduet totaled $15 million in the fourth quarter of 2004. Although Caduet's performance to date has been modest, it is slowly gaining traction due to increased product awareness and acceptance. This is evident in its total prescriptions in the U.S., which were 65% higher in the fourth quarter than in the first six months post-launch. We believe that Caduet is on its way to becoming an extremely useful treatment option as physicians are beginning to alter their longstanding practice of treating high blood pressure and high cholesterol as two distinct conditions. The FDA approved Caduet, the single-pill dual therapy of Lipitor (atorvastatin calcium) and Norvasc (amlodipine besylate), on January 30, 2004, and Pfizer launched Caduet in the U.S. in May. The first E.U. filing was submitted in France, the reference member state for Caduet, in the fourth quarter of 2003. We will be pursuing E.U. approvals for Caduet through the mutual recognition process. Caduet provides an opportunity to simultaneously address two of the most common risk factors of cardiovascular disease with the world's most prescribed branded blood-pressure medication-Norvasc-and lipid-lowering medication-Lipitor-in one pill. In September 2004, the FDA approved changes to the prescribing information for Lipitor and Caduet to include prevention of cardiovascular disease. The results of the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA) bring a critical new insight into the management of hypertensive patients-that hypertensive patients benefit from Lipitor in addition to blood-pressure-lowering therapy. On December 8, 2004, Pfizer announced that the independent ASCOT steering committee had decided to stop the study in its entirety due to favorable benefits being seen in patients receiving the Norvasc-based treatment regimen. The fully analyzed results of the study are anticipated in 2005. By current estimates, each year 9 million deaths around the world, equaling more than 75 million lost years of healthy life, may be attributed to suboptimal blood-pressure or cholesterol levels. Treatment guidelines advocate early and aggressive management of multiple risk factors for patients at increased cardiovascular risk. Q3) How is Norvasc performing? A3) Worldwide sales of Norvasc in the fourth quarter of 2004 totaled $1.253 billion, reflecting growth of 1% compared to the same period in 2003. The slower rate of growth compared to earlier quarters is attributable in part to patent expirations throughout the E.U., except for Italy, France, Sweden, and Switzerland. Norvasc maintains exclusivity in many markets globally, including the U.S., Japan, Canada, and Australia. Norvasc's performance in the U.S. throughout 2004 was strong, and prescription volumes reached a 52- week high in October 2004. Since its introduction in 1990, Norvasc has become the world's most- prescribed branded antihypertensive therapy and the fourth-largest- selling drug in the world. Its success has been driven by its outstanding efficacy, once-daily dosing, consistent 24-hour control of hypertension and angina, and excellent safety and tolerability. Overall, Norvasc has been studied in more than 400,000 patients and has been used in more than 30 billion patient days of therapy worldwide. Hypertension affects about 50 million Americans and one billion people worldwide. Currently 69% of American adults diagnosed with hypertension are not at their blood-pressure goal. Recent guidelines call for early, aggressive blood-pressure management and make clear that the majority of patients may require two or more medications to reach their blood-pressure targets. Recently reported randomized clinical trial results continue to highlight the beneficial effects of Norvasc. In November 2004, outcomes from the Pfizer-sponsored Comparison of Amlodipine versus Enalapril to Limit Occurrences of Thrombosis (CAMELOT) trial were published in The Journal of the American Medical Association. In the two-year study of patients with coronary artery disease and normal or well-controlled blood pressure, Norvasc-treated patients experienced 42% fewer hospitalizations for chest pain and 27% fewer coronary revascularization procedures, such as angioplasty and coronary artery bypass surgery, compared to patients receiving placebo. An intravascular ultrasound (IVUS) sub-study from the CAMELOT trial demonstrated that patients who received Norvasc showed no significant increase in the progression of plaque build-up in coronary arteries. On December 8, 2004, Pfizer announced that early indications from the landmark Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) showed that patients receiving a treatment regimen based on Norvasc experienced favorable cardiovascular benefits. As a result of these findings, the independent ASCOT steering committee decided to stop the trial early so that ASCOT investigators and patients can discuss their optimum hypertension treatment moving forward. Fully analyzed results of the study, involving nearly 20,000 patients with high blood pressure, are anticipated in 2005. Q4) What is the status of Exubera? A4) Exubera (inhaled insulin powder) is under development as a treatment for both type 1 and type 2 diabetes through a collaboration between Pfizer and Sanofi-Aventis. Pfizer is also collaborating with Nektar Therapeutics, developer of the inhalation device and formulation process for Exubera. Exubera has been studied in more than 3,000 patients, some for up to six years. As an effective alternative to insulin injections, Exubera has also been shown in clinical trials to be preferred by patients. This patient preference may encourage patient acceptance of, and compliance with, insulin therapy, thereby improving the health of diabetics and reducing the healthcare costs associated with the disease. An estimated 177 million people worldwide suffer from diabetes, now the fourth-leading cause of death in most developed countries. Annual costs associated with the disease are estimated at $186 billion worldwide. In February 2004, Pfizer and Sanofi-Aventis submitted a regulatory filing for Exubera in the E.U. Q5) What is the status of Revatio? A5) Revatio(TM) (the brand name for sildenafil citrate for pulmonary arterial hypertension) was submitted to the FDA and regulatory authorities in the Netherlands and Spain, the rapporteur and co-rapporteur sponsors, the European Medicines Agency (EMEA) and Health Canada in December 2004 as a treatment for pulmonary arterial hypertension (PAH). Subsequent to the U.S. filing, the FDA approved the company's request for an expedited review. Revatio has been designated an orphan drug by the EMEA. Sildenafil is the same active ingredient in Viagra(R), the world's leading erectile-dysfunction medication, which has been used by more than 23 million men worldwide because of its unsurpassed efficacy and safety. The Revatio dosing regimen is different from that for Viagra, and, to avoid confusion, Revatio tablets will have a color and shape different from those of Viagra tablets. PAH is a rare, aggressive, and life-shortening vascular disease for which new treatment options are desperately needed. Often referred to as high blood pressure of the lungs, PAH affects approximately 200,000 people in North America and Europe. In a large multinational clinical trial (SUPER 1), Revatio 20 mg taken three times daily was found to be effective in treating PAH. Patients treated with Revatio had improved physical functioning as demonstrated by increased walking distance over a six-minute time interval. Patients on Revatio also had a reduction in blood pressure in arteries of the lungs and an increase in cardiac heart output, both of which are critical in treatment of this disease. Q6) What is the status of the torcetrapib/Lipitor program? A6) A combination product of torcetrapib, a cholesteryl ester transfer protein (CETP) inhibitor, and Lipitor is now in global Phase III clinical trials for dyslipidemia that include 12,000 patients and are enrolling 13,000 patients in mortality and morbidity trials. The objective of the Phase III program is to demonstrate improved efficacy and comparable safety of the combination product versus Lipitor alone in a wide range of patients at cardiovascular risk with and without clinically apparent disease and across a variety of lipid abnormalities. The program is comprised of imaging trials that include intravascular ultrasound and carotid ultrasound, as well as a full range of blood-lipid efficacy studies. The program is designed to provide conclusive evidence of the benefits of raising HDL cholesterol through torcetrapib, in combination with the powerful LDL-cholesterol lowering and established benefits of Lipitor, beyond the well-demonstrated effects of Lipitor alone across patients with all types of lipid abnormalities. Demonstration of such benefit would provide support for use to torcetrapib/Lipitor in patients currently being treated with Lipitor and other statins. Additional scientific and mechanistic studies are also underway to broaden our understanding of the effects of CETP inhibition on lipid metabolism and atherosclerosis. These studies represent a major commitment by Pfizer to significantly advance our understanding of lipids and atherosclerosis to provide an important new tool for patients and prescribers in preventing and treating the global burden of cardiovascular disease. Data from a study assessing torcetrapib's impact on atherosclerosis in a rabbit animal model, recently reported at the American Heart Association 2004 Scientific Session, supports its potential efficacy for patients. Torcetrapib was found to inhibit CETP activity and raise HDL cholesterol, which strongly correlated with reduction in atherosclerosis in this rabbit model. Q7) What is the status of varenicline? A7) In 2000, it was estimated that there were 1.25 billion smokers worldwide and that nearly 5 million premature deaths/year globally were attributable to smoking. Seven out of ten smokers are contemplating quitting or actively want to quit; however, only 3-5% of patients can quit on their own. More effective treatments are needed for smoking cessation than are provided by currently available products. Varenicline is an innovative compound for smoking cessation. Neither a nicotine derivative nor an anti-depressant, varenicline was designed to selectively target the alpha 4-beta 2 nicotine receptors in the brain that stimulate the release of dopamine, which in turn results in the rewarding/reinforcing effects of smoking and leads to nicotine dependence. Varenicline is designed to have a unique dual benefit for the smoker to reduce the craving for cigarettes and the related withdrawal symptoms when quitting and to block the rewards from smoking that perpetuate dependence. In an early Phase II trial, almost half of smokers treated with varenicline stopped smoking. In this same trial, only one out of three smokers treated with Zyban stopped smoking. Varenicline complements Pfizer's leadership in providing innovative products to treat cardiovascular risk factors and the complications often associated with smoking. Varenicline is currently in full Phase III development worldwide. RESPIRATORY Q8) How is Spiriva performing? A8) Pfizer co-promotes Spiriva with the product's discoverer, Boehringer Ingelheim. Sales of Spiriva continue to outpace the overall chronic obstructive pulmonary disease (COPD) market. The product is currently available in more than 45 countries and is the best-selling COPD product in seven, including Germany and Australia. It has been introduced in the U.S. (June 2004), Italy (July 2004), and, most recently, Japan (December 2004). An anticholinergic medication, Spiriva is the first inhaled COPD treatment to provide significant and sustained improvements in lung function with once-daily dosing. Clinical trials have shown that patients with all stages of COPD, from mild to severe, can benefit from taking Spiriva. Trials have also demonstrated that Spiriva provided superior and sustained improvements in lung function, breathlessness, health-related quality of life, and exercise tolerance in COPD patients, and that the product provides sustained and significant improvements in lung function compared to ipratropium, the currently recommended first-line therapy outlined in many treatment guidelines. Spiriva has also been shown to significantly reduce COPD exacerbations and related health-resource burden versus usual care. New clinical data presented at the American College of Chest Physicians meeting in October 2004 confirm the role of Spiriva as first-line maintenance therapy in COPD. A double-blind, placebo-controlled study examined patients' reported reasons for stopping exercise in the setting of constant-work-rate bicycling. As a result of Spiriva-induced reductions in exertional dyspnea, patients are more likely to report leg discomfort rather than breathing discomfort as the limiting factor for stopping exercise. After six weeks, significantly fewer Spiriva-treated patients (28%) than placebo-treated patients (42%) identified breathing discomfort as the main reason for exercise limitation. Spiriva therapy also shifted the relative magnitude of both breathing discomfort and leg discomfort at the point of symptom limitation. Q9) How is Zyrtec performing? A9) Worldwide sales of Zyrtec totaled $349 million in the fourth quarter of 2004, reflecting a decline of 3% compared to the same period in 2003. Zyrtec continues to be the most prescribed antihistamine agent in a challenging market. The continued decline in new prescriptions in the antihistamine market is largely due to the wide availability of multiple, low-cost, over-the-counter branded and private-label loratadine (Claritin) products since December 2002 and continued aggressive cost shifting to consumers (such as through higher co-pays) by regional managed-care plans. Pfizer and UCB Pharma, who discovered Zyrtec, have substantial published data demonstrating the superior performance of Zyrtec versus Claritin, including two two-day environmental-exposure-unit studies in which Zyrtec provided twice the overall symptom relief of Claritin. More recently, new data demonstrating Zyrtec's superior performance versus Allegra in a two-day environmental-exposure unit were published in the January/February 2004 issue of Allergy and Asthma Proceedings and presented at the American College of Allergy, Asthma, and Immunology meeting in November 2004. Zyrtec has the broadest range of formulations and treats the widest age range of patients of any prescription antihistamine. Zyrtec is currently the only prescription antihistamine available on the market with both syrup and chewable forms. Q10) What is the status of Daxas (the brand name for roflumilast)? A10) Daxas is a phosphodiesterase-4 inhibitor, a class of compounds that provides anti-inflammatory action for respiratory diseases. The compound is currently being studied for both asthma and chronic obstructive pulmonary disease (COPD), two respiratory diseases associated with substantial morbidity and mortality. COPD affects 600 million people worldwide and kills more than 2.75 million people each year, according to estimates by the World Health Organization. The Global Burden of Disease Studies found that COPD was the sixth-most-common cause of death worldwide in 1990 and predicted that it would become the third-most-common cause of death by 2020. In the U.S., COPD is currently the fourth-leading cause of death (behind heart disease, cancer, and stroke), with death rates having increased 22% in the last decade. Asthma affects more than 300 million people worldwide and kills 180,000 people each year. Pfizer and our co-promotion partner Altana Pharma filed Daxas in the E.U. in February 2004 for both asthma and COPD. For other markets, the product is in late-stage development. UROLOGY Q11) How is Detrol/Detrol LA performing? A11) Worldwide sales of Detrol totaled $285 million in the fourth quarter of 2004, reflecting growth of 22% compared to the same period in 2003. Detrol's robust performance was due to successful launches of the once-daily formulation in Latin America and Asia and strong competitive positioning in the U.S. and E.U. It is the number-1 globally prescribed brand for overactive bladder (OAB), with more than 8.5 million patients worldwide since launch and a 53% market share. Detrol/Detrol LA has proven 24-hour efficacy across OAB symptoms, including urge incontinence, urgency, and frequency, resulting in excellent patient-reported outcomes. Detrol/Detrol LA also offers bladder selectivity with balanced receptor coverage, trusted tolerability, and proven safety profile. OAB is a highly prevalent condition, affecting 50-100 million people worldwide, with approximately 16% prevalence in adults in the U.S. and E.U. The market opportunity remains significant, as OAB is a vastly underreported and undertreated condition. As part of Pfizer's ongoing OAB research worldwide, the first validated screener, called the OAB-V8TM screener, has been developed and launched recently. OAB-V8TM screener is a simple-to-administer, easy-to-score, eight-question instrument that has been studied in 1,260 patients and validated in more than 20 languages. Q12) How is Viagra performing? A12) Worldwide sales of Viagra totaled $469 million in the fourth quarter of 2004, reflecting a decrease of 8% compared to the same period in 2003, due in large part to increased competition. Viagra maintains a strong leadership position, with a 71% worldwide market share of phosphodiesterase-5 inhibitors. Outside the U.S., where about half of Viagra sales are generated, the fourth quarter marked a competitive turning point, with 19% growth versus the third quarter of 2004. It remains one of the world's most recognized pharmaceutical brands. More than 130 clinical trials worldwide and more than six years of real-world experience have shown that Viagra provides hard, long-lasting erections that instill confidence in men, while maximizing both patient and partner satisfaction. Studies have shown that Viagra improves erections in up to 82% of men with erectile dysfunction (ED). Men taking Viagra also report a 77% improvement in their confidence to get and maintain an erection, compared to only 18% taking placebo. After four years of treatment, 96% of Viagra users and 92% of their partners report being highly satisfied with the product, with 95% of partners expressing a desire for their men to continue with Viagra treatment. A recently published study demonstrates that men taking Viagra under constant visual sexual stimulation reported a hard erection lasting on average for 33 minutes, compared to seven minutes for men on placebo. No other ED therapy has been proven to work better or faster than Viagra. Pfizer is confident that Viagra is uniquely positioned to retain its leading position. NEUROSCIENCE Q13) How is Aricept performing? A13) Aricept, approved for the treatment of symptoms of mild-to-moderate Alzheimer's disease (AD), continues to lead the AD market with a 59% worldwide market share and more than one billion cumulative patient days of therapy. In its eighth year on the U.S. market, the product continues to show strong new- and total-prescription growth, despite the launch of a new competitor, and achieved revenue growth of 21% in 2004. The product achieved record weekly new- and total-prescription volume of more than 30,000 and 94,000, respectively, in early December 2004. About 10% of people over 65 suffer from AD, including 4.5 million Americans. Aricept's strong market leadership has been built on a large body of clinical evidence supporting its excellent efficacy and tolerability and a keen customer focus. Cognition is typically the first area affected by AD. The benefits of early intervention with Aricept were confirmed in a study published in December 2004 in the Archives of Neurology. In this 24-week study of patients with early-stage or mild AD, Aricept significantly improved cognitive performance compared with placebo. Q14) How is Geodon performing? A14) Worldwide sales for Geodon totaled $143 million in the fourth quarter of 2004, reflecting growth of 36% compared to the same period in 2003. In the U.S., the product's new- and total-prescription shares continue to grow, with Geodon achieving its highest new-prescription share of 5.5% in October 2004. The product's October new-prescription growth of 36% compares to 6% growth of the overall U.S. antipsychotic market. Geodon is available in both an oral capsule and a rapid-acting intramuscular dosage form. Approximately 1% of the population suffers from schizophrenia. In the treatment of schizophrenia, clinical trials have demonstrated Geodon to be as effective as risperidone (Risperdal) and olanzapine (Zyprexa) in controlling both positive and negative symptoms, with a lower incidence of extra-pyramidal side effects than risperidone and significantly less weight gain and adverse changes in other metabolic indices than olanzapine. In a recent head-to-head study versus Zyprexa published in October 2004 in the American Journal of Psychiatry, Geodon demonstrated efficacy equivalent to Zyprexa in treating schizophrenia, while being associated with a lower incidence of weight gain and more favorable effects on lipid profile and other metabolic parameters. The Journal of Clinical Psychiatry published a head-to-head study comparing Geodon to risperidone in in-patients with schizophrenia or schizoaffective disorder. The study found that Geodon improved psychotic symptoms, was generally well tolerated, and demonstrated less effect on prolactin and weight than risperidone. Geodon is approved for acute bipolar mania in six countries, including the U.S., where the new indication was launched in November 2004. Pfizer filed for bipolar mania in the E.U. during the fourth quarter of 2004. As much as 3.5% of the population suffers from bipolar disorder, which, like schizophrenia, is a life-long illness. The use of Geodon in bipolar disorder represents a large and growing opportunity. In clinical trials for the treatment of bipolar mania, Geodon has been shown to control manic symptoms rapidly without inducing depression. A recent study published in the American Journal of Psychiatry showed that Geodon rapidly controls acute mania in as little as two days, with sustained control throughout the study. Geodon was found to be safe and well tolerated, with a low incidence of movement disorders. Q15) How is Lyrica (the brand name for pregabalin) performing? A15) Worldwide sales of Lyrica totaled $10 million in the fourth quarter of 2004, its first full quarter on the market. Lyrica was approved in July 2004 in the E.U. for treatment of peripheral neuropathic pain and as adjunctive therapy for partial epilepsy. The subsequent launches in Germany and the U.K. represent the most successful introductions of any neuropathic-pain or adjunctive-epilepsy product to date in those markets. Strong initial adoption is attributable to the significant unmet medical need in both conditions, the compelling clinical evidence supported by the Lyrica clinical program (the largest ever for a neuroscience compound, with more than 9,000 patients in clinical trials), and the positive initial results experienced by patients and physicians. Lyrica offers outstanding efficacy-demonstrated by rapid and robust pain reduction across its entire dose range of 150-600 mg-and favorable tolerability. New evidence-based guidelines for treatment of post-herpetic neuralgia from the American Academy of Neurology, published in the September 2004 issue of Neurology, endorsed Lyrica as a recommended first-line treatment. Another study, published in the December 2004 issue of Neurology, demonstrated Lyrica's efficacy in diabetic peripheral neuropathy. Lyrica was approved in Mexico in September 2004 for neuropathic pain and as adjunctive therapy for partial seizures. In the U.S., Lyrica was approved on December 30, 2004, and is the first FDA-approved product for the treatment of neuropathic pain associated with diabetic peripheral neuropathy and post-herpetic neuralgia. The product will be available to patients and physicians in the near future. In September 2004, Pfizer also received an approvable letter for Lyrica as adjunctive therapy in the treatment of partial seizures in adults and a non-approvable letter for the treatment of generalized anxiety disorder. Pfizer is working closely with the FDA to resolve open issues for both indications. Q16) How is Neurontin performing? A16) Worldwide sales for Neurontin totaled $481 million in the fourth quarter of 2004, reflecting a decline of 39% compared to the same period in 2003. This decline in sales is due to the at-risk launch of generic gabapentin by Ivax, Alpharma, and Teva in the U.S. Pfizer's Greenstone subsidiary followed suit by launching its own generic version of gabapentin. Pfizer has sued these and other companies for patent infringement, and if the court determines that these companies have infringed Pfizer's Neurontin patent, Pfizer will seek all available remedies and damages, including damages based on Pfizer's lost profits. Neurontin continues to be available in more than 100 countries and has been prescribed by more than 12 million patients since its initial approval in 1994. It is approved for adjunctive therapy in epilepsy in more than 100 countries and for treatment of a range of neuropathic-pain conditions in more than 60 countries. Q17) How is Relpax performing? A17) Worldwide sales of Relpax totaled $54 million in the fourth quarter of 2004, reflecting growth of 91% compared to the same period in 2003. Launched in more than 25 countries, the product continues to gain market share rapidly in the $2.3 billion global oral triptan market. In the U.S., Relpax new-prescription volume has grown by 73% versus December 2003, achieving 10.8% new-prescription share. Relpax has become the number-2 triptan in both switch prescriptions and new-to-market prescriptions, second only to sumatriptan. Relpax was launched in Canada, the fifth largest triptan market, in November 2004. Published data demonstrate that Relpax 40 mg provides better and more sustained relief from the symptoms of migraine than the market leader, sumatriptan (Imitrex), even if patients wait to treat and the pain is more intense. Relpax 40 mg also provides significantly more sustained relief than zolmitriptan (Zomig) or naratriptan (Amerge) based on two controlled studies. In addition, Relpax 40 mg has demonstrated efficacy in patients who have previously failed to obtain adequate relief with other prescription or with over-the-counter migraine medications, such as Imitrex, Maxalt, Excedrin Migraine, non-steroidal anti-inflammatory drugs, and Fiorinal/Fioricet. Recent data presented at the European Federation of Neurological Societies and the Migraine Trust International Symposium show that treating a migraine attack early with Relpax provides greater efficacy for migraine sufferers than waiting until the pain becomes more severe. The highest two-hour pain-free rates were seen among patients with mild pain taking Relpax 40 mg within 30 minutes of pain onset, and sustained pain-free rates were higher for patients treated with Relpax 40 mg when the pain was mild versus moderate-to-severe. The migraine market still represents a large untapped opportunity and a significant opportunity for continued Relpax growth. The prevalence of migraine is estimated to be 12% globally, with fewer than 50% of these patients being diagnosed and fewer than 20% receiving prescription medicine. Q18) How is Zoloft performing? A18) Worldwide sales of Zoloft totaled $959 million in the fourth quarter of 2004, reflecting growth of 7% compared to the same period in 2003. This strong performance in the fourth quarter followed a 6% decline in the U.S. in the third quarter, compared to the same quarter in 2003, which resulted from proposed regulatory changes to Zoloft's prescribing information and media coverage of the use of antidepressants in children and adolescents. Zoloft has been the number-one prescribed antidepressant in the U.S. since 2000. Physicians have written approximately 250 million Zoloft prescriptions for a variety of psychiatric disorders, accounting for more than 13 billion patient days of therapy. A large body of clinical data supports Zoloft's safety and effectiveness in its indicated uses. Zoloft is approved for six mood and anxiety disorders-major depression, panic disorder, obsessive-compulsive disorder (OCD) in adults and children, post-traumatic stress disorder, pre-menstrual dysphoric disorder (PMDD), and social anxiety disorder. For each of these indications except PMDD, Zoloft is approved for both acute and long-term use. Regulatory agencies in the U.S. and U.K. recently examined the safety of SSRIs in the treatment of depressed children and adolescents. In the U.K., clinical data in the adult population was also reviewed. The U.K. Medicines and Healthcare Products Regulatory Authority (MHRA) mandated that all SSRIs and serotonin/norepinephrine receptor inhibitors (SNRIs) except fluoxetine (Prozac) be contraindicated in children and adolescents with major depression. An advisory panel reaffirmed that Zoloft is safe and effective in children and adolescents with OCD. In December 2004, the MHRA proposed new prescribing information for SSRIs and SNRIs on suicidality and withdrawal of treatment in adults. In the U.S., following the recommendations of an advisory panel, on October 15, 2004, the FDA directed the makers of 33 currently marketed antidepressants, including both SSRIs and non-SSRI antidepressants, to include a black-box warning that antidepressants may increase the risk of suicidal behavior in children and adolescents. In the nine completed clinical trials of Zoloft in pediatric and adolescent patients, which included studies of Zoloft in children diagnosed with depression, OCD, or both, no suicides occurred. The trials found no statistically significant differences between Zoloft-treated patients and placebo controls in their rates of suicide attempts or ideation. Q19) What is the status of indiplon? A19) Indiplon is a unique GABA-receptor modulator for insomnia being developed by Pfizer and Neurocrine Biosciences. Indiplon has been developed in both immediate-release and modified-release forms to address multiple aspects of insomnia. Neurocrine Biosciences has announced that it will resubmit U.S. regulatory filings for both forms, previously submitted in the fourth quarter of 2004, to update the electronic formatting of the filings. Q20) What is the status of asenapine? A20) Asenapine is a novel psychotropic agent currently in Phase III development in more than 3,000 patients for the treatment of the acute symptoms and maintenance therapy of schizophrenia, as well as for treatment of the acute manic episodes associated with bipolar disorder. The compound is being developed in partnership with Organon. Based on Phase II results, asenapine has demonstrated strong efficacy and good toleration, with no clinically significant side effects. If approved, asenapine will enter a global antipsychotic market currently estimated at more than $13 billion in annual sales and growing about 13%. INFECTION Q21) How is Vfend performing? A21) Worldwide sales of the antifungal Vfend totaled $83 million in the fourth quarter of 2004, reflecting growth of 35% compared to the same period in 2003. Strong growth can be attributed to sustained demand and global launches. Vfend has been launched in 51 countries, including the U.S., and it is now the leading hospital antifungal product in France and Germany. Vfend is a new-generation azole antifungal with an extended spectrum of activity against both yeasts and moulds. The risk of serious fungal infections in hospitalized patients is growing. Fungal infections, especially in immunocompromised patients, are associated with high morbidity and mortality and require prompt and effective treatment. Vfend is approved in the U.S. for primary treatment of acute invasive aspergillosis, salvage therapy for rare but serious fungal infections caused by the pathogens Scedosporium apiospermum and Fusarium spp., and treatment of esophageal candidiasis. In Europe, Vfend is also approved for the treatment of serious, invasive, fluconazole-resistant Candida infections (including C. krusei). Vfend is available in oral tablets, powder for oral suspension, and intravenous forms and shows excellent bioavailability. As a result, there is the potential that some patients may be discharged from the hospital sooner, with orally administered therapy continuing at home. In the first quarter of 2004, Pfizer filed regulatory submissions in the U.S. and E.U. for use of Vfend in treatment of candidemia. In October 2004, European regulators issued a positive opinion on the application. In December 2004, the FDA approved Vfend for treatment of candidemia in non-neutropenic patients, for disseminated Candida infections in the skin, and for Candida infections in the kidney, abdomen, bladder wall, and wounds. Data presented at the American Society of Hematology meeting in December 2004 demonstrated that patients with invasive aspergillosis who were treated with Vfend as primary therapy required fewer days of intensive care compared to patients receiving standard treatment. Q22) How is Zithromax performing? A22) Worldwide sales of Zithromax, the world's largest-selling antibiotic, totaled $675 million in the fourth quarter of 2004, reflecting a decrease of 15% compared to the same period in 2003. This sales performance in part reflects a 6.7% reduction in global new-prescription demand for antibiotics. In the U.S., Zithromax remains the number-one branded product in all key indications in the respiratory-tract-infection market, with more than three times the market share of the second-leading branded competitor. Zithromax prescriptions in sinusitis, its newest indication in the U.S., grew 22% since launch and increased to 17.5% of all prescriptions for this indication in 2004. Zithromax is first-line therapy for a number of key indications, including acute exacerbations of chronic bronchitis, community-acquired pneumonia, sinusitis, and otitis media. Zithromax has a proven track record of clinical efficacy across the spectrum for mild/moderate RTI, unsurpassed safety, and a short therapeutic course that contributes to patient compliance and is cost effective. A novel microsphere formulation of azithromycin has been developed that allows for delayed release of drug in the small intestine instead of the stomach, maintaining tolerability. This delayed release, together with the long half-life of Zithromax microspheres, allows delivery of two grams of the product as a single dose. Data for this new formulation have been submitted to the FDA and other regulatory authorities for review. Zithromax is included among the Pfizer medicines being provided to aid the victims of the earthquake and tsunami that struck Asia and Africa on December 26, 2004. Q23) How is Zyvox performing? A23) Worldwide sales of Zyvox totaled $135 million in the fourth quarter of 2004, reflecting growth of 73% compared to the same period in 2003. While days of therapy for all anti-staphylococcal products have increased 14% worldwide in the past year, days of Zyvox therapy have increased more than 50%. Zyvox is now marketed in 62 countries. The clinical value of Zyvox is growing, due to the rising incidence of infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and multi-drug-resistant enterococci and their associated morbidity and mortality. Zyvox has proven efficacy in the treatment of patients with pneumonia and skin and soft-tissue infections, including diabetic foot infections, often caused by MRSA. The product has a unique mechanism of action that stops the initial stage of bacterial protein production, without which bacteria cannot multiply. This results in no cross-resistance with other antibiotics. Zyvox is available in intravenous and oral formulations. This allows for earlier discharge for some patients, who can switch from the intravenous Zyvox in the hospital to the oral form at home and thereby reduce their hospital costs. Zyvox is also approved for pediatric use. Data showing advantages of Zyvox continue to emerge. In October 2003, important data were presented at the Infectious Diseases Society of America meeting showing that Zyvox was more effective than vancomycin in treating patients with complicated skin and soft-tissue infections due to suspected or proven MRSA, with lower costs compared with vancomycin due to shorter intravenous therapy and reduced hospital stay. A post-hoc analysis of these MRSA patients with surgical-site infections was published in the American Journal of Surgery in December 2004. Patients treated with Zyvox had microbiologic success rates of 87% compared to 48% for patients on vancomycin. Q24) What is the status of UK-427,857? A24) UK-427,857 represents a novel mechanism of action, CCR-5 co-receptor antagonism. CCR-5 co-receptor antagonists form a sub-class of a broader group of HIV antiretrovirals known as entry inhibitors. Unlike current antiretroviral agents that work by inhibiting HIV replication within white blood cells, UK-427,857 works by blocking the human chemokine co-receptor CCR-5, which is expressed on the surface of human white blood cells, thereby preventing the virus from entering host cells. UK-427,857 has been shown in vitro to be effective against HIV strains resistant to the current classes of HIV antiretroviral agents, potentially addressing a significant unmet medical need in HIV therapy. Phase I studies have shown UK-427,857 to be well tolerated across a range of potential doses, and Phase II studies have shown UK-427,857's efficacy and safety as monotherapy in HIV patients. A clinical program is now underway in pursuit of an indication for the treatment of patients with HIV infection in combination with other antiretroviral agents. The global HIV/AIDS epidemic killed more than 3 million people in 2003. An estimated 5 million people acquired HIV during the year, bringing to 38 million the number of people living with the virus around the world (UNAIDS Report, July 2004). Pfizer is committed to bringing meaningful improvement to the lives of people living with HIV/AIDS and to those at risk around the world. OPHTHALMOLOGY Q25) How is Xalatan/Xalacom performing? A25) Worldwide sales of Xalatan/Xalacom totaled $353 million in the fourth quarter of 2004, reflecting growth of 23% compared to the same period in 2003. Xalatan/Xalacom outpaced the growth of the total anti-glaucoma market. Xalatan/Xalacom together hold leadership of the glaucoma market in dollar sales. Worldwide annual sales of Xalatan, the number 1 prescribed anti-glaucoma medication in the world, achieved the $1 billion milestone in sales in 2004. An estimated 67 million people suffer from glaucoma worldwide. Each year, more than 100,000 people in the U.S. are diagnosed with glaucoma, a group of eye diseases characterized by damage to the optic nerve, visual-field loss, and/or elevated intraocular pressure (IOP). Xalatan, a prostaglandin analogue used to lower the intraocular pressure associated with glaucoma and ocular hypertension, continues to lead the worldwide anti-glaucoma market and has displaced beta blockers as the accepted gold standard. It provides comprehensive IOP management by combining the benefits of powerful efficacy, superior tolerability and patient persistency, five-year safety data, and physician preference so physicians can achieve the outcome of preventing or delaying optic-nerve damage that can lead to blindness. Xalacom, a combination of Xalatan and the beta-blocker timolol, provides incremental efficacy for patients who have an insufficient response to monotherapy while maintaining the simplicity of a single daily dose. Future opportunity exists as, in the U.S., approximately one third of the diagnosed glaucoma patients are untreated and only 10-15% of the ocular hypertensive patients received treatment. An article published in the September 2004 issue of the American Journal of Ophthalmology compared the nocturnal effects of the once-daily beta-blocker timolol and Xalatan on IOP in patients with ocular hypertension or early glaucomatous changes. Although both treatments were effective in lowering IOP during the day, only Xalatan reduced IOP at night. These results provide support in our efforts to accelerate share gain from the large, remaining beta-blocker segment. The article "Risk Assessment in the Management of Patients with Ocular Hypertension," published in the September 2004 issue of the American Journal of Ophthalmology, addresses physicians' decisions about when to treat an ocular-hypertensive patient. The article establishes the concept of global risk assessment and translates the findings from the Ocular Hypertension Treatment Study into practical guidelines for initiation of treatment in ocular-hypertensive patients. As in cardiovascular disease, the concept of global risk assessment, when applied to glaucoma, may enable ophthalmologists to identify and treat patients earlier in the disease continuum to prevent the onset of glaucoma, further irreversible damage to the optic nerve, and loss of visual function. Q26) What is the status of Macugen? A26) Pfizer and Eyetech Pharmaceuticals, Inc., the discoverer of Macugen, are jointly developing and will jointly commercialize the product. Macugen is an aptamer that selectively binds to, and neutralizes, vascular endothelial growth factor for the treatment of age-related macular degeneration (AMD). The FDA approved Macugen for the treatment of neovascular (wet) age-related macular degeneration in December 2004. The product has been filed in the E.U., Canada, Australia, and Brazil. AMD is the leading cause of irreversible vision loss among Americans over 55 and occurs in both wet and dry forms. In wet AMD, blood vessels grow abnormally into the area beneath the retina. The wet form accounts for approximately 200,000 new cases annually, with a prevalence of 1.2 million cases in the U.S. alone. Positive Phase III results for Macugen in AMD, announced at the American Academy of Ophthalmology meeting in 2003, demonstrated benefit to a broad group of wet AMD patients irrespective of lesion subtype or size, unlike existing therapies. PRNewswire-FirstCall -- Jan. 19 SECOND AND FINAL ADD -- Q&A CONTINUES -- TO FOLLOW Source: Pfizer Inc Web site: http://www.pfizer.com/ ------- Profile: International Entertainment