This annual report summarizes Amgen's performance in 2000 and outlines goals for the future. Key points include:
- Amgen achieved strong financial results in 2000 and aims to more than double revenues and products on the market in the next five years.
- The company reaffirmed its commitment to its core values and adopted a shared aspiration to become the world's best human therapeutics company.
- Amgen hopes to launch four new products in the next 18 months, including ARANESP, anakinra, abarelix-depot, and SD/01, to treat conditions like anemia and cancer.
- The company expanded its R&D capabilities, grew its product pipeline, and plans to
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
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Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
2. Contents
Selected Financial Information 2
Letter to the Shareholders 4
Chronic Kidney Disease 14
Cancer 16
Rheumatoid Arthritis 18
Products and Product Candidates 20
Management’s Discussion and Analysis
of Financial Condition and Results of Operations 22
Quantitative and Qualitative Disclosures about Market Risk 27
Consolidated Financial Statements 28
Report of Ernst & Young LLP, Independent Auditors 45
Operating Subsidiaries 46
Board of Directors and Executive Officers 47
Corporate Information 48
3. We aspire to be
the best human
therapeutics
company. We will
live the Amgen Values
and use science
and innovation to
dramatically improve
people’s lives.
4. Selected Financial Information
Research and Development Expenses Amgen Staff
Net Income Stockholders’ Equity
Total Revenues Diluted EPS
($ in millions)
($ in millions) ($ in millions)
($ in millions)
00 $845.0 00 $4,314.5 00 7,326
00 $1.05
00 $3,629.4 00 $1,138.5
99 $822.8 99 $3,023.5 99 6,355
99 $1.02
99 $3,340.1 99 $1,096.4
98 $663.3 98 $2,562.2 98 5,585
98 $0.82
98 $2,718.2 98 $ 863.2
97 $630.8 97 $2,139.3 97 5,372
97 $0.59
97 $2,401.0 97 $ 644.3
96 $528.3 96 $1,906.3 96 4,709
96 $0.61
96 $2,239.8 96 $ 679.8
95 $451.7 95 $1,671.8 95 4,084
95 $0.48
95 $1,939.9 95 $ 537.7
94 $323.6 94 $1,274.3 94 3,396
94 $0.29
94 $1,647.9 94 $ 319.7
93 $255.3 93 $1,172.0 93 3,109
93 $0.33
93 $1,373.8 93 $ 383.3
92 $182.3 92 $ 933.7 92 2,363
92 $0.30
92 $1,093.0 92 $ 357.6
91 $120.9 91 $ 531.1 91 1,751
91 $0.08
91 $ 682.0 91 $ 97.9
91 92 93 94 95 96 97 98 99 00 91 92 93 94 95 96 97 98 99 00 91 92 93 94 95 96 97 98 99 00
91 92 93 94 95 96 97 98 99 00 91 92 93 94 95 96 97 98 99 00 91 92 93 94 95 96 97 98 99 00
Consolidated Statement of Operations Data
(In millions, except per share data)
Years ended December 31, 2000 1999 1998 1997 1996 1995 1994 1993 1992 1991
Revenues:
Product sales1 $ 3,202.2 $ 3,042.8 $ 2,514.4 $ 2,219.8 $ 2,088.2 $ 1,818.6 $ 1,549.6 $ 1,306.3 $ 1,050.7 $ 645.3
Other revenues 427.2 297.3 203.8 181.2 151.6 121.3 98.3 67.5 42.3 36.7
Total revenues 3,629.4 3,340.1 2,718.2 2,401.0 2,239.8 1,939.9 1,647.9 1,373.8 1,093.0 682.0
Research and development expenses 845.0 822.8 663.3 630.8 528.3 451.7 323.6 255.3 182.3 120.9
Selling, general, and administrative expenses 826.9 654.3 515.4 483.8 470.6 418.4 359.8 328.4 292.2 202.6
Other items, net2 (18.8) (49.0) (23.0) 157.0 — — 116.4 (13.9) (77.1) 129.1
Net income 1,138.5 1,096.4 863.2 644.3 679.8 537.7 319.7 383.3 357.6 97.9
Diluted earnings per share 1.05 1.02 0.82 0.59 0.61 0.48 0.29 0.33 0.30 0.08
Cash dividends per share — — — — — — — — — —
Consolidated Balance Sheet Data
(In millions)
At December 31, 2000 1999 1998 1997 1996 1995 1994 1993 1992 1991
Total assets $ 5,399.6 $ 4,077.6 $ 3,672.2 $ 3,110.2 $ 2,765.6 $ 2,432.8 $ 1,994.1 $ 1,765.5 $ 1,374.3 $ 865.5
Long-term debt 223.0 223.0 223.0 229.0 59.0 177.2 183.4 181.2 129.9 39.7
Stockholders’ equity 4,314.5 3,023.5 2,562.2 2,139.3 1,906.3 1,671.8 1,274.3 1,172.0 933.7 531.1
1
Due to Year 2000 contingency planning in the fourth quarter of 1999, the Company offered extended payment terms on limited shipments of EPOGEN® (Epoetin alfa) and NEUPOGEN®
(Filgrastim) to certain wholesalers. These Year 2000 related sales totaled $45 million, or $0.02 per share, in 1999.
2
Amounts primarily comprised of benefits and expenses related to various legal proceedings. The amounts in 2000 and 1994 include write-offs of acquired in-process research and
development of $30.1 million and $116.4 million, respectively. The amount in 2000 also includes a charitable contribution of $25 million to the Amgen Foundation. See Notes 4
and 11 to the Consolidated Financial Statements for a discussion of the amounts in 2000, 1999, and 1998. Other items, net, increased/(decreased) earnings per share by $0.00
in 2000, $0.03 in 1999, $0.01 in 1998, ($0.09) in 1997, ($0.10) in 1994, $0.01 in 1993, $0.04 in 1992, and ($0.08) in 1991.
2 3
5. DEAR FELLOW Amgen Values
Be science-based
•
SHAREHOLDER: Work in teams
•
Compete intensely and win
•
Create value for patients, staff, and stockholders
•
Trust and respect each other
•
Collaborate, communicate, and build consensus
•
Ensure quality
•
Be ethical
•
The year 2000 was one of accomplishment and growth for thought, we agreed on a shared aspiration to become the
Amgen, and the future has never looked more promising. world’s best human therapeutics company.
This year is off to a great start with our recent victory in the There is no single definition that captures what we mean
Aventis/TKT litigation regarding erythropoietin in the U.S. by “best.” We know it includes delivering a stream of innova-
District Court. In the next five years, we hope to more than tive products that dramatically improve people’s lives, being a
double the size of the company in terms of revenues and place where the best people choose to work, and outperform-
products on the market. We also will substantially expand the ing our peers in delivering value to shareholders. By adopting
number of patients we serve and the size of Amgen’s staff. such a broad aspiration, we are committing ourselves fully to
There are challenges, to be sure, in meeting our goals, but improving continuously along every important dimension of
we are confident that we have the people, the strategy, and Amgen’s activities.
the resources necessary to make our future even brighter The second goal was to prepare to launch a stream of
than our past. new products beginning in 2001, with a particular focus on
Reviewing the significant progress Amgen made toward ARANESP™ (darbepoetin alfa). Depending upon regulatory
each of the six goals established by our executive manage- approvals, we could launch four new products in the next 18
ment team after I became CEO last May provides a good months — ARANESP™, anakinra, abarelix-depot, and SD/01.
summary of our recent progress and plans for the future. That is why we have spent heavily on clinical development to
The first goal was to align the company around a ensure our products’ characteristics are widely and thoroughly
shared aspiration built from a common set of values. We tested and documented. We have prepared and submitted
reaffirmed our commitment to eight fundamental Amgen regulatory filings around the world to obtain the fastest and best
values developed several years ago: be science-based; approvals possible. We have worked hard to understand physi-
work in teams; compete intensely and win; create value for cians’ and other providers’ attitudes to be sure our messages
patients, staff, and stockholders; trust and respect each will be persuasive and reimbursement will be available, and we
other; collaborate, communicate, and build consensus; have built new field forces to ensure that our voice is heard.
ensure quality; and be ethical. We believe ARANESP™ represents a new standard of care
As a company, we also worked hard to develop a shared for treating anemia in chronic renal failure, and in other
aspiration. The pace of scientific innovation and medical settings. Amgen is determined to become the world leader in
understanding is accelerating every day, making a technology- treating patients with all types of anemia, one of the most
based foundation too limiting for us. At the same time, the under-recognized and under-treated of diseases. We estimate
competitive landscape is changing as the industry restructures the worldwide anemia market could be as large as $10 billion
and competition for innovative therapeutics increases in by 2005. Introducing ARANESP™ globally gives it the potential
intensity. In the face of these and other changes, we strongly to be Amgen’s biggest product ever.
agreed — as a company — that one approach would serve us Anakinra, interleukin-1 receptor antagonist (IL-1ra), is the
enduringly: focus our efforts on using science and innovation cornerstone of our inflammation franchise. We estimate the
to dramatically improve people’s lives. Broadening this market for biological therapies in rheumatoid arthritis could
4
6. Kevin W. Sharer
Chairman,
Chief Executive Officer,
and President
reach $3 billion by 2005. Anakinra is unique in that it will be the Our acquisition of Kinetix Pharmaceuticals was an impor-
only therapy that mitigates inflammation and reverses or tant step in continuing to build our small molecule capabilities.
reduces joint destruction by specifically blocking IL-1, a pivotal Choosing disease areas around which to cluster our product
cytokine. development activities was another important step. Increasing
Abarelix-depot is a prostate cancer treatment with a our R&D spending to nearly $1 billion in 2001, up from approx-
novel mechanism of action that will distinguish it from other imately $850 million in 2000, is yet another key toward
available therapies. In clinical trials, abarelix-depot rapidly achieving this goal.
reduces testosterone and follicle-stimulating hormone levels We are very pleased with our pipeline progress. One
without the troubling testosterone surge associated with other product application was filed in the U.S., and applications for
treatments. Abarelix-depot will compete in the hormonal two products were filed in the European Union, Canada,
therapy market for prostate cancer estimated to reach $1.5 Australia, and New Zealand. We started, or made the decision
billion by 2005 and is expected to be an important addition to to start, four registration trials and received one line extension.
our oncology franchise. One new product candidate already in clinical development
SD/01 is a longer-acting and therefore a less-frequently was in-licensed, and we in-licensed or acquired another eight
administered form of NEUPOGEN® (Filgrastim). We expect research and preclinical projects. We plan in 2001 to begin five
SD/01 to help more people successfully get through new product-registration and label-extension trials and file two
chemotherapy and stay out of the hospital by making new-product or label-extension applications in the U.S. and
protection from infection simpler with a once-per-cycle, “one- other countries. Also, we continue aggressive efforts to acquire
size-fits-all” configuration. Phase 3 trials of SD/01 have been product opportunities from outside Amgen.
completed, and we expect to file for regulatory approval of Goal four was to strengthen our organization capabilities
this therapy in the first half of 2001. and help our staff grow professionally. We did this with the
Our third goal was to expand our research and develop- addition of Roger Perlmutter, MD, PhD, as executive vice
ment capabilities, and grow and advance the product pipeline. president of Research and Development and George Morrow
R&D is the core of Amgen, and we made good progress in as executive vice president of Worldwide Sales and Marketing.
expanding our activities. We defined more clearly where to Roger Perlmutter formerly was executive vice president of
direct our discovery resources, added significant talent and Worldwide Basic Research and Preclinical Development for
leadership to our scientific and medical staffs, and grew our Merck Research Laboratories. George Morrow formerly was
pipeline. Our core technology base is in large molecules. Our president and CEO of GlaxoWellcome, North America. We also
plan is both to protect and enhance this strength, by expanding hired several additional executives with broad industry experi-
to monoclonal antibody therapeutics, while continuing to grow ence in research and development at the vice president level.
our small molecule capabilities. We believe this three-modality Despite these additions, we have more work to do in the
approach is the one that best enables Amgen to capitalize on area of developing our staff. The Executive Committee is
the increased understanding of disease mechanisms and focusing more time and effort on this issue than ever before,
therapeutic targets emerging in the postgenomic era. and I expect to be able to report significant progress on this
5
7. Accomplishments
Received favorable judgement in patent litigation relating to erythropoietin
•
Completed a phase 3 clinical trial in Europe of ARANESP™ (darbepoetin alfa) in patients with solid tumors and anemia
•
Completed phase 3 clinical trials for abarelix-depot in patients with prostate cancer, and the license application was submitted to the FDA
•
Successfully completed phase 3 clinical trials of SD/01 in patients with cancer
•
Submitted the license application in Europe for IL-1ra in patients with rheumatoid arthritis
•
In-licensed epratuzumab, a monoclonal antibody that may be a potential treatment for patients with non-Hodgkin’s lymphoma
•
Enhanced our small molecule capabilities through the acquisition of Kinetix
•
Sales and Marketing teams prepared for the launch of ARANESP™ and other late-stage product candidates
•
Received FDA licensing of our Longmont, Colorado, manufacturing facility
•
front in next year’s annual report. Another area in which we Looking forward, sales and earnings are expected to accel-
need to make greater progress is diversity. We have made erate beginning in 2001, fueled by new product launches. By
some progress—for example, we now have eight women vice 2005, five or more new products may be launched that could
presidents, up from three a year ago. But we are redoubling drive product sales to the $8 to 9 billion range.
our efforts and taking a more broad-based and energetic Don Rice and Paul Reason recently joined our board,
approach to fully tap the potential of the widest range of bringing a wealth of industry and government experience. At
possible contributors to Amgen’s work. We are committed to the same time, Gordon Binder, our CEO from October 1988 to
making advances in this area. May 2000, has retired and left our board. Gordon’s dedication
Our fifth goal was to be successful in the Aventis/TKT to the company and our purpose was unmatched, and all the
erythropoietin patent litigation. We won in the U.S. District people at Amgen deeply appreciate his tireless efforts and the
Court thanks to a magnificent effort by our legal team, led by extraordinary results Amgen achieved under his leadership.
General Counsel Steve Odre and Vice President of Intellectual
Property Stuart Watt. This successful defense of our
intellectual property was important, not only for Amgen but for
our entire industry.
Goal six was to deliver on our short-term financial prom-
ises and, at the same time, invest wisely for the future. Amgen
has an outstanding record in providing value to shareholders,
and we are working hard to continue to deliver. We achieved
our profit targets in 2000 even though U.S. NEUPOGEN® sales
were somewhat short of expectations. NEUPOGEN® is used in
support of patients undergoing chemotherapy, and some
changes in chemotherapy usage patterns have resulted in less
NEUPOGEN® usage in those settings. However, overall, more
patients than ever are receiving NEUPOGEN®, and we expect
NEUPOGEN® sales to grow this year.
As I write this letter today, Amgen’s stock price has grown
by 12 percent in the last twelve months while stocks in Kevin W. Sharer
general have performed worse, with the S&P 500 declining by
13 percent. As we now prepare to launch ARANESP™, I recall Chairman,
the historic day in December 1998 when arbitrators affirmed Chief Executive Officer,
Amgen’s exclusive rights to ARANESP™. Since that day, and President
Amgen’s stock price has increased by 195 percent versus the
performance of the S&P 500, which increased by 1 percent. March 13, 2001
6
9. chronic kidney vitality
Danielle Treatment
End-Stage gives Danielle
Renal the vitality and
Disease freedom to live
more actively,
which includes
disease freedom
enjoying her
grandson more.
4 5
10. cancer determination
Focused on
Jeff
completing his
Non-Hodgkin’s
treatments,
Lymphoma
Jeff also is
determined and
confident that he
confidence
will soon get
back to the
ballpark with
his son.
6 7
11. rheumatoid independence
Janis Janis hopes
Rheumatoid that treatment
Arthritis will give her
agility and
independence for
those special
arthritis agility
morning visits
with not only her
mom but also her
own daughter.
8 9
12. CHRONIC EPOGEN ® (Epoetin alfa)
End-Stage Renal Disease Patients
KIDNEY DISEASE Anemia
It is believed that more than 3 million people in the United lating red blood cells the heart has to work harder and that this
States have signs of chronic kidney disease. The approx- condition may result in cardiovascular disease. The potential
imately 250,000 of these people whose disease has benefit of less frequent dosing may allow more of these
progressed to kidney failure must undergo regular dialysis patients to have their anemia treated.
treatments to remove wastes from their blood. These patients Amgen is now introducing a program called the Renal
have a condition known as end-stage renal disease (ESRD). Anemia Management Period (RAMP) to nephrologists, the doc-
Nearly 12 years ago, Amgen’s first product, EPOGEN®, tors who manage kidney disease patients. RAMP helps doctors
revolutionized the treatment of anemia for ESRD patients identify anemic patients with CRI sooner and manage their
undergoing dialysis. EPOGEN® supplements dialysis patients’ anemia earlier. Additionally, Amgen is supporting the devel-
inadequate supply of erythropoietin, a protein produced by the opment of guidelines by the National Kidney Foundation for the
kidneys to stimulate oxygen-carrying red blood cell supply. treatment of all stages of kidney disease —the Kidney Disease
Appropriate anemia management lessens fatigue, improves Outcomes Quality Initiative (KDOQI). We believe that earlier
cognitive and physical functioning, and has allowed many treatment of anemia could have important benefits for patients.
dialysis patients to regain the vitality and freedom to participate A further complication for patients with chronic kidney
more actively in life, without the need for blood transfusions. failure is the development of secondary hyperparathyroidism.
Amgen’s late-stage product candidate, ARANESP ™ In patients with this condition, the parathyroid glands detect
(darbepoetin alfa), may represent an important advance for low levels of calcium and increase production of parathyroid
anemic patients with chronic kidney disease. Through hormone (PTH) — the most important regulator of body calcium.
molecular engineering, Amgen scientists developed ARANESP™ Abnormally high levels of PTH may result in many comp-
to permit less-frequent dosing than EPOGEN®. lications, including weak bones and abnormal calcium
Just as important, because we have retained exclusive deposits in blood vessels and other soft tissues.
rights for ARANESP ™, Amgen may be able to work with doctors Amgen’s calcimimetics program may offer benefits to
earlier to help simplify anemia management for many more patients with chronic kidney disease and secondary hyperpara-
patients in the U.S. and around the world. If approved by thyroidism. Encouraging data from phase 2 studies, published
regulatory agencies, doctors may start treating anemia from in the past year, suggest that treatment with small-molecule
chronic kidney disease with ARANESP ™ early in the disease’s calcimimetics results in dose-dependent decreases in PTH
progression, before patients require dialysis treatment. This levels and may provide effective reduction of calcium levels.
early stage of kidney disease is known as chronic renal insuf- Amgen is proud to be developing and delivering important
ficiency (CRI). therapeutics to growing numbers of patients worldwide and is
Of the more than 3 million patients with chronic kidney dedicated to remaining at the forefront of renal care.
disease in the U.S., more than 1 million patients have CRI, and
350,000 of these patients with CRI could be anemic. Only a
small proportion of these patients are treated for their anemia,
despite a growing awareness that when there are fewer circu-
14
13. Dr. Allen Nissenson, MD
Professor of Medicine, Director, Dialysis Program
UCLA School of Medicine
Chair, Amgen Nephrology National Advisory Board
“The best way to illustrate the remarkable breakthrough for
dialysis patients that EPOGEN® has been is to relate a story
about one of my patients.
Congenital malformations in his urinary tract led to kidney
failure when he was 14. He then started hemodialysis. Two
years later he received a cadaveric kidney transplant. But after
one year of slow rejection, he returned to hemodialysis. At age
19, he moved to Los Angeles and was struggling to graduate
from high school. On top of kidney failure, he was severely
anemic. Without blood transfusions his hemoglobin was
7.0-8.0 g/dL; twice that level would have been normal for his
age. To have enough energy to go to school and concentrate
on his work, he required two to three blood transfusions
monthly. Even with these, his hemoglobin rarely was higher
than 10 g/dL.
In 1986 he agreed to participate in the phase 3 clinical trial
with Epoetin alfa. Within 12 weeks of starting, his hemoglobin
was 12 g/dL, and he said he felt as well as he had before his
kidneys failed. He has since received no blood transfusions,
although he has continued with hemodialysis. In 1991 he had
hip replacement surgery to repair damage done by the high
doses of steroids he had received during his kidney transplant
experience. Prior to surgery, he donated two units of his own
blood, to be held in the blood bank. What a remarkable
reversal—from requiring blood transfusions just to get by to
donating his own blood prior to surgery! His hip replacement
was successful. He went on to get his bachelor’s degree in
accounting and is now a practicing CPA. Just last year he
was married.
This story illustrates the huge contribution EPOGEN® has
made to the lives of kidney patients. ARANESP™, by requiring
less frequent administration, may be another significant step for-
ward in the treatment of anemia in patients with kidney disease.”
15
14. CANCER NEUPOGEN® (Filgrastim)
Chemotherapy Patients
Neutropenia
Each year, more than 1 million people are diagnosed with require pain medication and have reduced quality of life.
cancer in the United States alone. Since 1991, Amgen’s Another of Amgen’s product candidates, keratinocyte growth
NEUPOGEN® has helped patients with cancer undergoing factor (KGF), is a recombinant form of a naturally-occurring
myelosuppressive chemotherapy battle one of the treatment’s growth factor that stimulates the development of mucosal
serious possible side effects—a reduction in white blood cells cells. Early clinical trials suggest KGF may offer benefit for
called neutrophils. Neutropenia —the resulting condition — can patients who experience mucositis following chemotherapy
lead to infection and to delays in chemotherapy delivery. In the and radiotherapy.
past year, Amgen made significant progress with three addi- Amgen is now broadening its cancer franchise to include
tional product candidates that may lessen some of the serious the discovery and development of novel cancer therapeutics to
side effects associated with chemotherapy treatment. target and eradicate tumor cells.
Pivotal clinical trials of SD/01 were completed in women Abarelix-depot, the first long-acting gonadotrophin-
with breast cancer. This innovative product candidate is a sus- releasing hormone antagonist, is a potential cancer therapeutic
tained duration form of NEUPOGEN®. If approved by regulatory that Amgen licensed from Praecis Pharmaceuticals in 1999.
agencies, SD/01 may benefit patients by permitting less- Researchers from Amgen and Praecis are collaborating on the
frequent dosing than the current daily dosing of NEUPOGEN®. development of abarelix-depot to treat men with prostate
SD/01 may be effective given as infrequently as once per cycle cancer, aiming to limit cancer cell stimulation by lowering
of myelosuppressive chemotherapy. Chemotherapy cycles are testosterone levels. Abarelix-depot is currently under regula-
often scheduled every three to four weeks. As a result, patients tory review for the treatment of patients with prostate cancer
may benefit from protection from infections, as manifested by and also is being studied in women with endometriosis, a
fever and neutropenia. commonly occurring, painful, and potentially debilitating pelvic
ARANESP™ (darbepoetin alfa), in addition to its potential disorder affecting women of childbearing age.
use in kidney disease treatment, is being evaluated for treat- In the past year, Amgen licensed a novel cancer therapeu-
ment of cancer-related anemia. Many patients with cancer tic antibody, epratuzumab, from Immunomedics. Epratuzumab
suffer from anemia. This anemia may be caused by the cancer is currently being evaluated for its ability to treat indolent (low
itself or may be a side effect of chemotherapy. Phase 2 clinical grade) and aggressive non-Hodgkin’s lymphoma (NHL). In NHL,
trials suggest that treatment with ARANESP™ of patients with cells in the lymphatic system become abnormal. NHL can start
cancer-related anemia may be effective given once weekly or in any of the many parts of the body where there is lymphatic
once every three weeks. tissue and spread to almost any part of the body.
Cancer treatments such as chemotherapy and radio- These efforts illustrate Amgen’s continued dedication to
therapy are also often toxic to the mucosal cells lining the improving the lives of patients with cancer.
mouth and the gastrointestinal tract, resulting in ulceration of
the mucosal lining— mucositis. This condition results in painful
sores in the mouth and along the length of the gastrointestinal
tract that may prevent patients from eating. Patients frequently
16
15. Colorized micrograph of colon cancer,
prepared following surgical resection.
Bob Radinsky, PhD
Preclinical Cancer Researcher
Amgen
“Amgen is committed to turning the unprecedented possibil-
ities of science into the realities of therapeutic cancer
treatment. It’s a commitment supported by Amgen’s substan-
tial resources in areas ranging from exploratory research and
cancer biology to clinical oncology and development. Fulfilling
Amgen’s aspiration to be the best human therapeutics
company demands more than the success we have had in
cancer supportive care. It demands that we produce solutions
that make us the therapeutic partner of choice in cancer treat-
ment. This is why I recently left academia to join Amgen.
Amgen uses a broad spectrum of approaches to develop
cancer therapeutics, including small molecule, antibody, and
protein approaches. Supporting this work, the company has
made major investments in genomics, proteomics, gene
expression analysis, small molecule science, antibody tech-
nologies, and kinase biology. Our researchers work closely
with Amgen’s preclinical and clinical oncology groups to expe-
dite the development of novel cancer therapies. All researchers
likewise support the in-licensing of exciting new cancer thera-
peutic candidates.
Before joining Amgen, I worked for 11 years as a tenured
cancer researcher at the University of Texas M.D. Anderson
Cancer Center. My work there focused on host/tumor interac-
tions mediating tumor cell survival, growth, and angiogenesis
during the spread of cancer cells to distant organs in the body.
The opportunity to continue my translational cancer
research at a science-based company with a clear commit-
ment to targeted cancer therapeutics was, simply, too great to
pass up. As a PhD molecular and cellular cancer biologist who
has worked in all aspects of cancer research (from laboratory
bench to bedside), I have sworn to helping patients first.
Working at Amgen, I believe I can help more patients than in
any other way.”
17
16. RHEUMATOID ARTHRITIS
More than 6 million people worldwide have rheumatoid induce production of other cytokines and enzymes that cause
arthritis (RA), a systemic disease that commonly involves much of RA’s pain, swelling, and destruction. Preclinical stud-
inflammation of small joints with bone and cartilage destruc- ies have demonstrated that IL-1 plays the dominant role in
tion. This course of the disease eventually may lead to disability bone and cartilage destruction. Additionally, clinical evidence
and decreased life expectancy. has shown that patients with bone erosion have higher levels
In RA, the inflamed joint lining may invade and damage of IL-1 in their joints. Amgen has two potential candidates in
bone and cartilage, while inflammatory proteins stimulate the development to block each of these cytokines.
release of enzymes that actually digest bone and cartilage. Anakinra, a recombinant form of naturally-occurring IL-1
This results in loss of shape and alignment of the joint, pain, receptor antagonist (IL-1ra, a protein the body produces to reg-
and reduced mobility. X-rays of patients with rheumatoid ulate IL-1) is the most advanced product candidate. Clinical
arthritis show that the most rapid deterioration of joint function studies suggest that by binding to IL-1 receptors, anakinra
often occurs within the first few years of the disease, leaving a appears to interfere with the action of excess IL-1 and may help
small window of opportunity for intervention before irreversible regulate the inflammatory imbalance between IL-1 and IL-1ra.
damage may occur. Clinical trials suggest that anakinra may reduce the progres-
Though joint erosion can begin early in RA, more than half sion of joint destruction in patients with RA. Long-term studies
the people with this debilitating disease are undiagnosed or also suggest that patients who continue on anakinra for longer
not seeking treatment. While there is no cure for this disease, periods may have a further slowing in the rate of disease pro-
doctors traditionally have used drugs originally developed for gression. Amgen has submitted regulatory files for the
use in other therapeutic areas — such as cancer treatment and approval of anakinra for the treatment of rheumatoid arthritis
organ transplantation — to reduce swelling, alleviate pain and patients around the world.
stiffness, and preserve joint function for patients with RA. Still, Amgen’s second product candidate for RA, soluble TNF-
there remains a clear unmet medical need. Many doctors say receptor type I (sTNF-RI), is in early studies to assess its
that now is a promising time to be treating patients with RA effectiveness in blocking the impact of TNF-α in patients with
given the potential of new biological therapies. Nonetheless, RA. Another clinical trial is evaluating the effectiveness of
fewer than 10 percent of patients with RA receive these newer anakinra and sTNF-RI together in treating patients with RA.
drugs, and many may suffer the progression of RA. Amgen is committed to advancing the science of rheuma-
Cytokines are proteins that deliver chemical messages tology and hopes to soon offer an important new treatment to
among cells. Cytokines activate immune responses to fight off improve the lives of people affected by the serious and debili-
infections and decrease tissue injury and cell death. But in tating disease of rheumatoid arthritis.
patients with RA, there is persistent activation of the immune
system, which leads to an overabundance of certain cytokines
that induce structural damage and inflammation. The two key
cytokines in RA are Interleukin-1 (IL-1) and Tumor Necrosis
Factor-alpha (TNF-α). These two cytokines act together to
18
17. Bone
IL-1β
Activity of IL-1β and TNF-α as proinflammatory Pannus
cytokines in rheumatoid joints. Cartilage
Synovial Synovial
membrane membrane
Synovial (joint) cavity
Pannus
Cartilage
Capsule
TNF-α
Wim B. van den Berg, PhD
Inflammation Researcher
University Medical Center
Nijmegen, The Netherlands
“As an inflammation researcher, I am convinced of the prom-
ise of a new therapy that targets and selectively blocks
interleukin-1 (IL-1). This therapy may provide improved thera-
peutic impact in RA patients whose inflamed joints produce
increased levels of this cytokine that drives the devastating
joint erosion of the disease.
The potency of therapy with Amgen’s product candidate,
anakinra, a recombinant form of naturally-occurring interleukin-
1 receptor antagonist (IL-1ra), has been consistently shown in
arthritis models. In preclinical studies, reaching sufficient levels
of IL-1ra appears to block progression of joint inflammation and
fully prevent activation of erosive enzymes, called metallopro-
teinases, and the resulting cartilage destruction. Moreover,
results from studies in RA patients suggest that treatment with
IL-1ra may reduce joint erosion.
Studies also suggest that IL-1 is more potent than another
cytokine involved in RA, TNF-α, in inducing cartilage and bone
erosion. It appears that IL-1 is a critical mediator in TNF-driven
arthritis, since IL-1 blocking appears to fully prevent TNF-
induced pathology. In addition, IL-1 production that occurs
independently of TNF-α is seen in many forms of arthritis.
Further preclinical studies also suggest that erosive arthritis
cannot be induced in IL-1 deficient mice, in contrast to findings
in TNF-deficient mice. However, spontaneous destructive
arthritis appears to occur in mice lacking IL-1 receptor antago-
nist (IL-1ra), illustrating that insufficient control of IL-1 by its
natural inhibitor, IL-1ra, causes joint destruction.
To me, this is an exciting time in the science and treatment
of rheumatoid arthritis when a significant and much needed
advance may be met by blocking the devastating erosion
caused by excess levels of IL-1 in the joints of RA patients.”
19
18. Amgen Products and Product Candidates
Amgen is discovering and developing a stream of product candidates using science and innovation to dramatically improve people’s lives.
By leveraging its core biology and protein expertise and aggressively pursuing outside innovation, Amgen’s research and development strategy
is focused on four main therapeutic areas—chronic kidney disease, cancer, inflammation, and neurology/metabolism—and three potential
patient-delivery modalities—protein, small-molecule, and antibody therapeutics.
Amgen late-stage Amgen early-stage Amgen late-stage Amgen early-stage
Amgen products 1 product candidates 2 product candidates 3 Amgen products 1 product candidates 2 product candidates 3
Disease Description Disease Description
CHRONIC KIDNEY DISEASE INFLAMMATION
Anemia A decrease in the normal amounts Rheumatoid arthritis A disease characterized by pain and Anakinra Soluble tumor
EPOGEN ® ARANESP TM
of red blood cells that develops in (Epoetin alfa) (darbepoetin swelling of the joints in which the body’s (Interleukin-1 necrosis factor-
chronic kidney disease patients due alfa) natural immune system attacks healthy receptor receptor type I
to a decrease in the production of joint tissue as it would foreign cells antagonist, IL-1ra) (sTNF-RI)
erythropoietin by the kidneys
NEUROLOGY/METABOLISM
Secondary Excessive production of parathyroid Calcimimetic
hyperparathyroidism hormone program
Obesity The storage of excess fat in the body Leptin
CANCER Parkinson’s disease A motor system disorder characterized Neuroimmuno-
by tremors of hands, arms, legs, jaw, philin program
Neutropenia A decrease in a type of white blood and face; stiffness of the limbs and
NEUPOGEN ® SD/01
cell called a neutrophil that may occur (Filgrastim) trunk; slowness of movement; and
following chemotherapy treatment impaired balance and coordination
resulting in an increased risk of
infection
OTHER
Anemia A decrease in the normal amount ARANESP ®
of red blood cells that may occur (darbepoetin alfa) Osteoporosis A disease of the skeleton in which the Osteoprotegerin
following chemotherapy treatment amount of calcium present in the (OPG) program
or due to the cancer itself bones slowly decreases to the point
where the bones become brittle and
Stem cell A procedure in which the bone prone to fracture
NEUPOGEN ®
transplantation marrow destroyed by high doses (Filgrastim)
of chemotherapy or radiation is Endometriosis A painful disease wherein fragments Abarelix-depot
STEMGEN ®
replaced by stem cells that (Ancestim) 4 of endometrial tissue implant outside
produce white blood cells, red the uterine cavity, usually in other
blood cells, and platelets areas of the pelvis, in women
Aplastic anemia A failure of the bone marrow to Primary Excessive production of parathyroid Calcimimetic
STEMGEN ®
generate cells (Ancestim) hyperparathyroidism hormone by a benign tumor program
Mucositis Inflammation of the mucosal lining Keratinocyte Hepatitis C A liver disease caused by the INFERGEN ®
of the gastrointestinal tract as a growth factor hepatitis C virus (HCV), which is (Interferon
result of cancer treatment found in the blood of persons who alfacon-1)
(KGF)
have this disease
Bone metastases Invasion of bone by cancer cells Osteoprotegerin
originating in other parts of the body (OPG) program
that may induce bone destruction
Prostate cancer A slow-growing malignant tumor in men Abarelix-depot
that arises in the prostate gland and can
spread to other parts of the body
Non-Hodgkin’s A heterogeneous group of Epratuzumab
lymphoma lymphoproliferative malignancies that
usually originate in lymphoid tissues 1
Denotes marketed products in the United States and other countries.
2
Denotes product candidates in phase 3 clinical trials or filed with regulatory agencies.
and may spread to other organs
3
Denotes product candidates in phase 1 or 2 clinical trials.
4
STEMGEN® is marketed in Canada and Australia only.
The Company’s ability to develop and commercialize new products is highly uncertain because very few pharmaceutical/biotechnology research and development products
ever produce a commercial product. In addition, while the Company routinely seeks to obtain patents for its products, the protection offered by patents and patent appli-
cations may be challenged, invalidated, or circumvented. The Company believes that in some cases third party patent rights could limit product commercialization.
20 21
19. Management’s Discussion and Analysis
of Financial Condition and Results of Operations
Liquidity and Capital Resources authorized the Company to repurchase up to $2 billion of common
stock between January 1, 2001 and December 31, 2002. The
The Company had cash, cash equivalents and marketable securi- amount the Company spends on and the number of shares repur-
ties of $2,028.1 million at December 31, 2000, compared with chased each quarter varies based on a variety of factors, including
$1,333.0 million at December 31, 1999. Cash provided by operat- the stock price and blackout periods in which the Company is
ing activities has been and is expected to continue to be the restricted from repurchasing shares.
Company’s primary source of funds. In 2000, operations provided
$1,634.6 million of cash compared with $1,226.9 million in 1999. To provide for financial flexibility and increased liquidity, the
Company has established several sources of debt financing. As of
December 31, 2000, the Company had $223 million of unsecured
Cash, Cash Equivalents and Marketable Securities long-term debt securities outstanding. These unsecured long-term
($ in millions)
debt securities consisted of: 1) $100 million of debt securities that
bear interest at a fixed rate of 6.5% and mature in 2007 under a
$500 million debt shelf registration (the “Shelf”), 2) $100 million of
debt securities that bear interest at a fixed rate of 8.1% and mature
in 2097 and 3) $23 million of debt securities that bear interest at a
fixed rate of 6.2% and mature in 2003. Under the Shelf, all of the
remaining $400 million of debt securities available for issuance
may be offered under the Company’s medium-term note program
with terms to be determined by market conditions.
00 $2,028.1
99 $1,333.0
98 $1,276.0
97 $1,026.5
The Company’s sources of debt financing also include a com-
96 $1,077.0
96 97 98 99 00
mercial paper program which provides for unsecured short-term
borrowings up to an aggregate face amount of $200 million. As of
December 31, 2000, commercial paper with a face amount of
Capital expenditures totaled $437.7 million in 2000 compared with $100 million was outstanding. These borrowings had maturities of
$304.2 million in 1999. The Company anticipates spending less than two months and had effective interest rates averaging
approximately $450 million to $550 million in 2001 on capital proj- 6.7%. In addition, the Company has an unsecured $150 million
ects and equipment to expand the Company’s operations. credit facility that expires on May 28, 2003. This credit facility sup-
ports the Company’s commercial paper program. As of December
The Company receives cash from the exercise of employee stock 31, 2000, no amounts were outstanding under this line of credit.
options and proceeds from the sale of stock by Amgen pursuant
to the employee stock purchase plan. In 2000, employee stock The primary objectives for the Company’s investment portfolio are
option exercises and proceeds from the sale of stock by Amgen liquidity and safety of principal. Investments are made to achieve
pursuant to the employee stock purchase plan provided $333.7 the highest rate of return to the Company, consistent with these
million of cash compared with $248.8 million in 1999. Proceeds two objectives. The Company’s investment policy limits invest-
from the exercise of employee stock options will vary from period ments to certain types of instruments issued by institutions with
to period based upon, among other factors, fluctuations in the investment grade credit ratings and places restrictions on maturi-
market value of the Company’s stock relative to the exercise price ties and concentration by type and issuer.
of such options.
The Company believes that existing funds, cash generated from
The Company has a stock repurchase program primarily to reduce operations and existing sources of debt financing are adequate to
the dilutive effect of its employee stock option and stock purchase satisfy its working capital and capital expenditure requirements for
plans. In 2000, the Company repurchased 12.2 million shares of its the foreseeable future, as well as to support its stock repurchase
common stock at a total cost of $799.9 million, and in 1999, the program. However, the Company may raise additional capital from
Company repurchased 27.1 million shares of common stock at a time to time.
cost of $1,024.7 million. In December 2000, the Board of Directors
22
20. Management’s Discussion and Analysis
of Financial Condition and Results of Operations
prior year. This increase was primarily due to higher demand, prin-
cipally driven by the administration of higher doses and growth in
Total Assets
($ in millions)
the U.S. dialysis patient population. The administration of higher
doses of EPOGEN® was principally due to dialysis providers man-
aging more patients into the hematocrit range of 33 to 36 percent
as recommended by the Dialysis Outcomes Quality Initiative, as
well as the use of hemoglobin instead of hematocrit to measure
red blood cell volume.
EPOGEN® Sales
00 $5,399.6
99 $4,077.6 ($ in millions)
98 $3,672.2
97 $3,110.2
96 $2,765.6
96 97 98 99 00
Results of Operations
Product Sales 00 $1,962.9
99 $1,759.1
Product sales were $3,202.2 million in 2000, an increase of $159.4 98 $1,382.0
97 $1,160.7
million or 5% over the prior year. In 1999, product sales were 96 $1,071.9
96 97 98 99 00
$3,042.8 million, an increase of $528.4 million or 21% over the
prior year. Quarterly product sales are influenced by a number of
factors, including underlying demand, wholesaler inventory man-
agement practices and foreign exchange effects. NEUPOGEN® (Filgrastim) Worldwide NEUPOGEN® sales were
$1,223.7 million in 2000, a decrease of $32.9 million or 3% from
EPOGEN® (Epoetin alfa) EPOGEN® sales were $1,962.9 million in the prior year. This decrease was primarily due to the adverse
2000, an increase of $203.8 million or 12% over the prior year. impact of wholesaler buying patterns, including Year 2000-related
This increase was primarily due to higher demand, which was prin- sales to wholesalers in the fourth quarter of 1999 for which the
cipally driven by growth in the U.S. dialysis patient population and Company provided extended payment terms, as well as adverse
to a lesser extent, the effect of higher prices. Sales in 2000 were foreign exchange effects. The Company believes these factors
adversely impacted by Year 2000-related sales to wholesalers in were partially offset by a mid-single digit rate increase in demand,
the fourth quarter of 1999 for which the Company provided which includes the effect of higher prices in the U.S. In 1999,
extended payment terms and, the Company believes, by dialysis worldwide NEUPOGEN® sales were $1,256.6 million, an increase of
provider inventory drawdowns in 2000 of additional 1999 year-end $140.0 million or 13% over the prior year. This increase was pri-
stockpiling. The Company believes that some of this dialysis marily due to higher demand, which includes the effect of higher
provider stockpiling may have been due to Year 2000 concerns prices in the U.S., and the impact of approximately $29 million of
and year-end contract expirations. In 1999, EPOGEN® sales were Year 2000-related sales to wholesalers in the fourth quarter of
$1,759.1 million, an increase of $377.1 million or 27% over the 1999 for which the Company provided extended payment terms.
23
21. Management’s Discussion and Analysis
of Financial Condition and Results of Operations
NEUPOGEN® Sales Total Product Sales
($ in millions) ($ in millions)
00 $1,223.7 00 $3,202.2
99 $1,256.6 99 $3,042.8
98 $1,116.6 98 $2,514.4
97 $1,055.7 97 $2,219.8
96 $1,016.3 96 $2,088.2
96 97 98 99 00
96 97 98 99 00
Other Product Sales Other product sales primarily consist of Cost of Sales
INFERGEN® (Interferon alfacon-1). INFERGEN® sales were $14.5 mil- Cost of sales as a percentage of product sales was 12.8%, 13.2%
lion in 2000, a decrease of $11.7 million or 45% from the prior and 13.7% for 2000, 1999 and 1998, respectively. The decreases
year. In 1999, INFERGEN® sales were $26.2 million, an increase of in these percentages were primarily due to increased manufactur-
$10.4 million or 66% over the prior year. INFERGEN® was launched ing efficiencies.
in October 1997 for the treatment of chronic hepatitis C virus
infection. There are other treatments, including combination ther- Research and Development
apy, for this infection against which INFERGEN® competes. The In 2000, research and development expenses increased $22.2
Company cannot predict the extent to which it will maintain its million or 3% over the prior year. This increase was primarily due
share or further penetrate this market. to higher staff-related costs necessary to support ongoing
research and product development activities and higher clinical
Corporate Partner Revenues trial costs. These increases were substantially offset by a reduction
In 2000, corporate partner revenues increased $84.8 million or 53% in clinical manufacturing and product licensing costs. In 1999,
over the prior year. In 1999, corporate partner revenues increased research and development expenses increased $159.5 million or
$33.5 million or 26% over the prior year. These increases were pri- 24% over the prior year. This increase was primarily due to product
marily due to amounts earned from Kirin-Amgen, Inc. related to the licensing and development costs related to the collaboration with
development program for ARANESPTM (darbepoetin alfa), the PRAECIS PHARMACEUTICALS INCORPORATED and higher staff-
Company’s novel erythropoiesis stimulating protein. related costs necessary to support ongoing research and product
development activities.
24
22. Management’s Discussion and Analysis
of Financial Condition and Results of Operations
Selling, General and Administrative Interest and Other Income
In 2000, selling, general and administrative (“SG&A’’) expenses In 2000, interest and other income increased $57.9 million or 66%
increased $172.6 million or 26% over the prior year. This increase over the prior year. This increase was primarily due to gains realized
was primarily due to higher staff-related costs and outside market- on the sale of certain equity securities in the Company’s portfolio
ing expenses as the Company continues to support its existing and higher interest income generated from the Company’s invest-
products and prepares for anticipated new product launches. In ment portfolio as a result of higher average cash balances and
1999, SG&A expenses increased $138.9 million or 27% over the higher interest rates. In 1999, interest and other income increased
prior year primarily due to higher staff-related costs and outside $42.6 million or 93% over the prior year. This increase was princi-
marketing expenses as the Company prepared for anticipated new pally due to the absence of write-downs recorded in 1998 of certain
product launches. non-current assets, primarily marketable equity securities.
Income Taxes
Selected Operating Expenses The Company’s effective tax rate was 32.0%, 30.0% and 29.5%
(as a Percent of Product Sales)
for 2000, 1999 and 1998, respectively. The tax rate in all three
28.4%
years reflected the tax benefits from the sale of products manufac-
27.0%
26.4%
26.4%
25.8%
tured in the Company’s Puerto Rico manufacturing facility. The
25.3%
Company’s tax rate has increased as a result of increased taxable
22.5%
21.8%
21.5%
20.5%
income combined with a provision in the federal tax law that caps
tax benefits associated with the Company’s Puerto Rico operations
at the 1995 income level. In addition, the 2000 tax rate increased
13.6%
13.7%
13.6%
13.2%
12.8%
as a result of the write-off of acquired in-process research and
91 $97.9
development, which is not deductible for tax purposes.
92 $319.7
93 $357.6
94 $537.7
95 $644.3
R&D
SG&A
Cost of Sales
96 97 98 99 00
Other Items, Net
Other items, net consisted of three non-recurring items: 1) legal
awards associated with the spillover arbitration with Johnson &
Johnson, 2) a write-off of acquired in-process research and devel-
opment associated with the acquisition of Kinetix Pharmaceuticals,
Inc. and 3) a charitable contribution to the Amgen Foundation.
See Note 4 to the Consolidated Financial Statements.
25
23. Management’s Discussion and Analysis
of Financial Condition and Results of Operations
Financial Outlook For 2001, total product sales are expected to grow in the mid to
high teens, cost of sales is expected to be in the range of 11.5%
In December 1999 and early 2000, the Company filed regulatory to 12.5% of total product sales, corporate partner revenues are
submissions for the use of ARANESP TM in patients with chronic renal expected to be approximately the same as in 2000, research and
insufficiency and chronic renal failure in the U.S., the European development expenses and SG&A expenses are each estimated to
Union, Canada, Australia and New Zealand. The Company antici- be in the range of 25% to 27% of total product sales, the effective
pates selling ARANESP TM, if approved, in most of these markets tax rate is expected to be approximately 34%, and earnings per
beginning in 2001. Because the Company is unable to predict the share is expected to grow in the mid teens.
timing and the extent to which health care providers in the U.S.
may transition from administering EPOGEN® to ARANESP TM, 2001 Estimates of future product sales, operating expenses and earn-
sales guidance for EPOGEN® and ARANESP TM will be provided on a ings per share are necessarily speculative in nature and are difficult
combined basis. The Company expects the percentage increase to predict with accuracy.
of 2001 sales of EPOGEN® and ARANESP TM combined over 2000
EPOGEN® sales to be in the range of high teens to low twenties. Except for the historical information contained herein, the matters
Patients receiving treatment for end stage renal disease are cov- discussed herein are by their nature forward-looking. Investors are
ered primarily under medical programs provided by the federal cautioned that forward-looking statements or projections made by
government. Therefore, EPOGEN® sales may also be affected by the Company, including those made in this document, are subject to
future changes in reimbursement rates or a change in the basis for risks and uncertainties that may cause actual results to differ mate-
reimbursement by the federal government. In addition, ARANESP TM rially from those projected. Reference is made in particular to for-
sales will be affected by government and private payor reimburse- ward-looking statements regarding product sales, earnings per
ment policies. share and expenses. Amgen operates in a rapidly changing environ-
ment that involves a number of risks, some of which are beyond the
In 2001, the Company expects the NEUPOGEN® sales growth rate Company’s control. Future operating results and the Company’s
to be in the high single digits. The Company believes that there is stock price may be affected by a number of factors, including,
a trend in some cancer settings towards the use of chemotherapy without limitation: (i) the results of preclinical and clinical trials; (ii)
treatments that are less myelosuppressive. Chemotherapy treat- regulatory approvals of product candidates, new indications and
ments that are less myelosuppressive may require less NEUPOGEN®. manufacturing facilities; (iii) reimbursement for Amgen’s products
Future NEUPOGEN® demand is dependent primarily upon penetra- by governments and private payors; (iv) health care guidelines and
tion of existing markets and the effects of competitive products. policies relating to Amgen’s products; (v) intellectual property mat-
NEUPOGEN® usage is expected to continue to be affected by cost ters (patents) and the results of litigation; (vi) competition; (vii) fluc-
containment pressures from governments and private insurers on tuations in operating results and (viii) rapid growth of the Company.
health care providers worldwide. In addition, reported NEUPOGEN® These factors and others are discussed herein and in the sections
sales will continue to be affected by changes in foreign currency appearing under the heading “Business - Factors That May Affect
exchange rates. In both domestic and foreign markets, sales of Amgen” in the Company’s Annual Report on Form 10-K for the
NEUPOGEN® are dependent, in part, on the availability of reim- year ended December 31, 2000, which sections are incorporated
bursement from third party payors such as governments (for herein by reference.
example, Medicare and Medicaid programs in the U.S.) and private
insurance plans. Therefore, NEUPOGEN® sales may also be affect-
ed by future changes in reimbursement rates or changes in the
bases for reimbursement.
INFERGEN® (Interferon alfacon-1) was launched in October 1997
for the treatment of chronic hepatitis C virus infection. There are
other treatments, including combination therapy, for this infection
against which INFERGEN® competes. The Company cannot predict
the extent to which it will maintain its share or further penetrate
this market.
26
24. Quantitative and Qualitative Disclosures about Market Risk
Interest income earned on the Company’s investment portfolio is are sensitive to changes in interest rates. For the Company’s invest-
affected by changes in the general level of U.S. interest rates. The ment portfolio and debt obligations, the tables present principal
Company’s short-term borrowings effectively bear interest at cash flows and related weighted-average interest rates by expect-
variable rates and therefore, changes in U.S. interest rates affect ed maturity dates. Additionally, the Company has assumed its
interest expense incurred thereon. The Company had reduced this available-for-sale debt securities, comprised primarily of corporate
exposure to interest rate changes by entering into an interest rate debt instruments and treasury securities, are similar enough to
swap agreement, which expired during 2000, that effectively aggregate those securities for presentation purposes. For the
changed the interest expense incurred on a portion of its short-term interest rate swap, the tables present the notional amount and
borrowings to a fixed rate. Changes in interest rates do not affect weighted-average interest rates by contractual maturity date. The
interest expense incurred on the Company’s long-term borrowings notional amount is used to calculate the contractual cash flows to
because they all bear interest at fixed rates. The following tables be exchanged under the contract.
provide information about the Company’s financial instruments that
Interest Rate Sensitivity
Principal Amount by Expected Maturity as of 12/31/99
Dollars in Millions, Fair Value
Average Interest Rate 2000 2001 2002 2003 2004 Thereafter Total 12/31/99
Available-for-sale debt securities $ 376.8 $ 721.8 $ 177.7 $ 17.0 $ 5.0 — $ 1,298.3 $ 1,293.6
Interest rate 6.3% 6.4% 6.5% 6.0% 5.6% —
Commercial paper $ 100.0 — — — — — $ 100.0 $ 100.0
Interest rate 6.4% — — — — —
Long-term debt — — — $ 23.0 — $ 200.0 $ 223.0 $ 216.6
Interest rate — — — 6.2% — 7.3%
Interest rate swap related to
commercial paper issuances:
Pay fixed/receive variable $ 50.0 — — — — — $ 50.0 $ 0.3
Avg. pay rate 5.3% — — — — —
Avg. receive rate 6.0% — — — — —
Principal Amount by Expected Maturity as of 12/31/00
Dollars in Millions, Fair Value
Average Interest Rate 2001 2002 2003 2004 2005 Thereafter Total 12/31/00
Available-for-sale debt securities $ 780.4 $ 740.6 $ 232.3 $ 118.5 $ 60.0 — $ 1,931.8 $ 1,950.2
Interest rate 6.6% 6.7% 7.0% 6.5% 7.0% —
Commercial paper $ 100.0 — — — — — $ 100.0 $ 100.0
Interest rate 6.7% — — — — —
Long-term debt — — $ 23.0 — — $ 200.0 $ 223.0 $ 222.0
Interest rate — — 6.2% — — 7.3%
The Company is exposed to equity price risks on the marketable portion of equity securities included in its portfolio of investments
entered into for the promotion of business and strategic objectives. These investments are generally in small capitalization stocks in the
biotechnology industry sector. The Company typically does not attempt to reduce or eliminate its market exposure on these securities.
An 80% adverse change in equity prices would result in a decrease of approximately $178 million and $72 million in the fair value of the
Company’s available-for-sale marketable equity securities at December 31, 2000 and 1999, respectively.
27