Wyeth reported record financial results for 2006, with net revenue increasing 9% to $20.4 billion and net income growing 14% to $4.2 billion. The company achieved over $1 billion in annual sales for six product franchises. Research and development efforts led to the filing of four new drug applications. Wyeth continues to invest in innovation through its pharmaceutical, biotech, vaccine and consumer healthcare divisions to address unmet medical needs and drive future growth.
2. Financial Highlights
Year Ended December 31,
2005
2006
(In thousands except per share amounts)
Net Revenue $18,755,790
$20,350,655
Net Income 3,656,298
4,196,706
Diluted Earnings per Share 2.70
3.08
Dividends per Common Share 0.94
1.01
Total Assets 35,841,126
36,478,715
Stockholders’ Equity 11,994,369
14,652,755
Wyeth at a Glance
Wyeth is one of the world’s largest medicines and animal health care products
research-based pharmaceutical and health that improve the quality of life for people
care products companies. It is a leader in worldwide. The Company’s major divisions
the discovery, development, manufacturing include Wyeth Pharmaceuticals, Wyeth
and marketing of pharmaceuticals, biotech- Consumer Healthcare and Fort Dodge
nology products, vaccines, non-prescription Animal Health.
A Special Report
On the Cover on Alzheimer’s Disease Contents
Motivational life coach Meredith Millions of people around the 1 Chairman’s Report to Stockholders
Froemke takes Enbrel for her world are coming face to face
7 Wyeth’s Pipeline for Innovation
rheumatoid arthritis. “Within six with Alzheimer’s disease, a
weeks of therapy, I felt like a new neurodegenerative disorder that 8 An Expanding and Promising
human being,” she marvels. “It’s robs sufferers of their memories, Near-Term Pipeline
given me back my mobility and my their identities and, ultimately,
12 The War on Alzheimer’s
life.” Her daughter, Lauren, also their lives. Wyeth is at the forefront
has benefited from an innovative of an extraordinary effort to 32 Selected Products from Wyeth
Wyeth medicine after being find new and better medicines to
vaccinated with Prevnar to help control this disease’s symptoms 33 Directors and Officers
prevent invasive pneumococcal and, potentially, to halt or even
34 Financial Review
disease. Wyeth is a leader in reverse its progression. A special
innovation through use of report beginning on page 12 36 Corporate Data
pharmaceutical, biotech and takes an in-depth look at Wyeth’s
IBC Mission, Vision and Values
vaccine technologies. war on Alzheimer’s.
3. Chairman’s Report to Stockholders
Robert Essner, Chairman and Chief Executive Officer
am pleased to report that “We once again delivered on our • Revenue from all of our
I 2006 was an excellent year biotechnology products in
commitment to expand our
for Wyeth. Building on our 2006 reached $5.7 billion,
growth, strengthen our position
strong performance in 2005, representing about a third
we once again delivered on our of Wyeth Pharmaceuticals’
for the future and lead the way
commitment to expand our total revenue and making
to a healthier world.”
growth, strengthen our posi- Wyeth the fourth largest
tion for the future and lead biotechnology company in
the way to a healthier world. the world.
Driven by the steady growth of our key products, Wyeth • In January 2007, we received an approvable letter
reported record revenue. We filed four New Drug Appli- from the U.S. Food and Drug Administration (FDA)
cations (NDA) for new products, demonstrating solid for Pristiq, a serotonin-norepinephrine reuptake
productivity from our research and development (R&D) inhibitor for the treatment of major depressive disor-
efforts. Overall, our new product pipeline significantly der, which will be launched with a specific focus
expanded and advanced. By maximizing productivity, on women.
controlling costs and delivering high value, we helped • Wyeth Consumer Healthcare provided an important
position Wyeth to address the economic realities of a revenue contribution and positioned itself for future
changing health care environment. And, as we have growth through the introduction of innovative new
done every year, during 2006 we continued to listen to products such as Advil PM.
our stakeholders, to learn from them and to apply those • Sales for Fort Dodge Animal Health rose 6 percent,
lessons to our business. driven by increased revenue from its companion
Highlighted below are some of Wyeth’s significant animal and livestock products. The division’s robust
achievements during 2006 and in early 2007. These new product pipeline is expected to continue as a
demonstrate the success of our efforts and our potential source of strong growth.
to build upon them: • We increased our dividend to stockholders for the
• Wyeth’s 2006 net revenue increased 9 percent to second consecutive year, demonstrating the confi-
nearly $20.4 billion, a record high for the Company. dence we have in our Company’s future and in the
Pro forma earnings grew 14 percent, the second strength of its financial resources.
consecutive year of double-digit growth. An in-depth In the section that follows this report, you will
review of our 2006 performance is provided in read about how we’re striving to improve world health
Wyeth’s 2006 Financial Report, the companion piece and sustain our growth through a near-term pipeline
to this Annual Review. of innovative products. And in a special feature story
• We achieved annual sales of more than $1 billion for on an area of enormous unmet need – Alzheimer’s
each of six core product franchises: Effexor, Prevnar, disease – you will read about how Wyeth researchers
Protonix, Enbrel, Wyeth Nutrition and the Premarin are seeking critical breakthroughs for patients, their
family – demonstrating the breadth and diversity caregivers and society.
of our portfolio.
1
4. Wyeth Pharmaceuticals “Our pharmaceutical business Worldwide net sales
for Enbrel, the number
delivered outstanding results by
ur pharmaceutical
O one biotechnology product
business delivered
extending the reach of our products in its category in North
outstanding results by
America, grew 20 percent
and enhancing their potential
extending the reach of our
to more than $4.4 billion.
products and enhancing their for further growth.” This includes sales in the
potential for further growth.
United States and Canada
At the same time, Wyeth
that are recorded by our
Pharmaceuticals took signifi-
marketing partner Amgen Inc. While all regions con-
cant steps to increase the efficiency and responsiveness
tributed to growth, strongest results came from Europe,
of its sales organization and to expand a variety of
where sales increased 33 percent, making Enbrel
educational efforts for patients.
the number one ranked biotechnology product there.
Effexor and Effexor XR continued as the world’s
Wyeth Nutrition is a world leader in the develop-
number one antidepressant franchise. Sales reached
ment, manufacture and distribution of scientifically
$3.7 billion in 2006, an increase of 8 percent. An
based nutritional products for infants and toddlers.
additional indication for use of Effexor XR in panic
Wyeth Nutrition continued to grow at double-digit
disorder contributed to growth while the results of
rates in 2006. Global sales grew to $1.2 billion, an
the PREVENT study provided further evidence of the
increase of 15 percent over 2005. The two regions
sustained efficacy of Effexor XR in treating major
enjoying the fastest growth were Asia/Pacific, which
depressive disorder.
comprised nearly 60 percent of global nutritional sales
Prevnar (Prevenar outside the United States) was
and grew 23 percent, and Latin America, which made
the number one selling vaccine in the world, with
up 16 percent of global sales and grew 15 percent.
42 million doses manufactured and net sales of nearly
Having recently celebrated its 90th anniversary,
$2 billion, an increase of 30 percent over 2005. Strong
Wyeth Nutrition has evolved into a significant interna-
global usage of Prevenar accelerated in 2006 as nine
tional player with 60 affiliates selling our products
more countries, including Germany, Mexico and
around the world. The Company markets its premium
the United Kingdom, added Prevenar to their National
product line under the Gold banner and, in late 2006,
Immunization Programs (NIP). In total, 16 countries
was first to market with an innovative new product
have incorporated Prevenar into their NIPs, and
called Gold with lutein, which seeks to protect the eyes
growing evidence of the vaccine’s high value creates
of infants. To meet increasing demand for providing
opportunities for further expansion.
infants and toddlers with high-value products like the
Protonix, for erosive acid reflux disease, grew
Gold line, Wyeth Nutrition increased its manufacturing
7 percent to approximately $1.8 billion. During the
capacity in Mexico and began construction of an
year, RENEW, an innovative patient educational
expanded facility in the Philippines.
program for Protonix, was launched, providing sample
starter medications and educational materials to
facilitate discussions between patients and their physi-
cians and to help ensure patient compliance over the
longer term.
2
5. Wyeth remained a global leader in hormone Three growth drivers – Advil, Centrum and
therapies and was the U.S. market leader as sales of the Caltrate – benefited significantly from this strategy.
Premarin family of products increased 16 percent The Advil franchise grew 7 percent around the world,
globally and 21 percent in the United States. New data largely fueled by new marketing efforts. In Canada,
published in 2006 helped to further clarify the benefits Advil increased its market share and became the leader
and risks of hormone therapy for women, and Wyeth in the analgesic category for the first time. The Cen-
currently is working with physicians and their patients trum family of vitamin products achieved 4 percent
to appropriately address patient needs based on the sales growth, driven by innovations in Europe and
emerging data. growth in the age 50+ population. Centrum Advantage
Zosyn (Tazocin outside the United States) contin- was launched in the Canadian market in 2006.
ued to be the largest selling I.V. antibiotic worldwide Caltrate grew 3 percent largely due to international
with global net sales of $972 million, a 9 percent expansion.
increase over 2005. The success of Zosyn is attributa- Overall, international sales increased 2 percent
ble to its clinical efficacy and its ability to help while U.S. sales declined 3 percent. The decline in
hospitals control the emergence of resistant bacteria. the United States primarily resulted from the ongoing
Tygacil, our new antibiotic product, also delivered net impact of legislative restrictions on sales of pseu-
sales growth during the year. Since its launch in 2005, doephedrine-containing cough/cold formulations. In
it has gained 55 worldwide regulatory approvals response to these restrictions, Wyeth Consumer
and now is available in 33 markets. Tygacil is particu- Healthcare transitioned most of its products to an
larly important in hospitals for patients infected alternative active ingredient. This reformulation is
with common as well as more dangerous resistant expected to impact sales favorably in 2007. Outside
infectious pathogens in complicated skin/skin- the United States, a number of major international
structure and intra-abdominal infections. markets enjoyed double-digit growth, including
All these products require the right selling model Canada, China, Colombia, Mexico, Portugal, Taiwan,
for a changing health care environment. We’re pleased Thailand and Venezuela.
to report that the new primary care selling model we Wyeth Consumer Healthcare was particularly
implemented in the United States last year is working successful in achieving operating efficiencies to fund
well. In 2006, we jumped from No. 8 to No. 1 in the new investments and increase net income. Innovation
Health Strategies Group’s annual primary care physi- also was a key contributor to growth, highlighted by
cian audit, which demonstrates physicians’ initial the successful launch of Advil PM. Opportunities
satisfaction with our new structure. for future growth now are being developed, including
an innovative Caltrate food-grade line in China, the
start of a consumer health care business in Russia,
Wyeth Consumer Healthcare
and an intense research and development effort to
xcluding the impact of revenue from Solgar
E deliver new forms of Advil.
Vitamin and Herb, which was divested in 2005,
sales for Wyeth Consumer Healthcare increased
1 percent to more than $2.5 billion in 2006, spurred
largely by a strong focus on supporting our core
global brands.
3
6. Fort Dodge Animal Health capture, and the simplification of clinical trial material
shipments and processes through a strategic alliance
ales of our Fort Dodge Animal Health products
S with a leading, worldwide logistics provider.
moved closer to $1 billion, reaching $936 million
We continued to realize solid results from our
and increasing 6 percent over the prior year. In
R&D organization, drawing upon our expertise in three
2006, Fort Dodge received pan-European regulatory
distinct discovery platforms: small molecules, biologics
approval to market ProMeris/ProMeris Duo, products
and vaccines. In 2006, Wyeth filed NDAs for Viviant,
offering flea and tick protection for dogs and flea protec-
for prevention of postmenopausal osteoporosis; Pristiq,
tion for cats. Approval in the United States is expected
for non-hormonal treatment of moderate to severe
in the first half of 2007. Another key achievement was
vasomotor symptoms associated with menopause;
the U.S. launch of Suvaxyn PCV2 One-Dose, a vaccine
Torisel, for patients with advanced renal cell carcinoma,
for the prevention of porcine circovirus, a disease that
which received priority review status; and bifeprunox –
leads to a wasting syndrome in pigs. In the face of global
filed with our partner Solvay Pharmaceuticals – for the
concerns over avian influenza, Fort Dodge received
treatment of schizophrenia. In addition, we submitted
approval for Poulvac Flufend, a new inactivated reverse
regulatory applications for a reformulation of BeneFIX,
genetics vaccine for poultry that addresses the potential
one of our hemophilia agents, as well as for a new adult
pandemic strain of the avian influenza virus.
granule-dose formulation of Protonix, and we received
regulatory approval for new dosing recommendations
Research and Development
for Rapamune in high-risk renal transplant patients.
ur greatest challenge at Wyeth is to create
O
Wyeth also is seeking to expand its presence in the con-
breakthrough medicines that serve the needs traceptive market with Lybrel, currently awaiting final
of patients in an increasingly competitive envi- FDA approval. Lybrel is a novel, continuous-use oral
ronment. From a research and development standpoint, contraceptive that is designed to provide significant
that challenge requires thinking and acting differently benefits in terms of menstrual-cycle regulation.
in discovering and advancing to market potentially During the year, we successfully advanced 15 new
important compounds. That is why we have instituted a molecular entities and two new vaccine constructs
new Learn and Confirm paradigm for drug development from discovery into development. In total, over the past
– a two-phase approach to streamlining the traditional six years, 75 new drug candidates were placed into devel-
multiple phases of development. This effort places opment, the majority having potential to be first- or
greater emphasis on high-performing teams, rapid best-in-class therapies. That has made Wyeth a leading
decision making and improved clinical trial designs. company within our industry peer group in discovering
Other accomplishments include the creation of a global novel molecules and advancing them rapidly into clinical
network of 10 early clinical development centers to development. We also believe that our pipeline is among
optimize our global patient mix, the streamlining of the most robust in the industry. Others share our positive
clinical data collection processes using electronic data views. For example, early in 2007, R&D Directions
magazine recognized Wyeth as the company with the best
central nervous system product pipeline in the industry.
4
7. In 2007, we expect to “We continued to realize solid results Success will come not
submit several important just in the laboratory
from our R&D
filings, including Viviant, for but also on the regulatory
organization, drawing upon
the treatment of osteoporosis; front and through the
Aprela, for the treatment development of strong part-
our expertise in three
of menopausal symptoms and nerships with patient
distinct discovery platforms …”
prevention of postmenopausal groups, government, regula-
osteoporosis; methylnaltrex- tory agencies, and scientists
one subcutaneous, for opioid- in industry and academia.
induced constipation in advanced medical illness; We must encourage additional research, accelerated and
methylnaltrexone I.V., for post-operative ileus; and informed new drug reviews, and more aid to caregivers
Tygacil, for use in community-acquired pneumonia and who bear the brunt of this health scourge. You will read
hospital-acquired pneumonia. about some of the patients and their caregivers in this
report. These family members are courageous beyond
measure in doing everything in their power to try to care
A Special Report on Alzheimer’s Disease Research
for their loved ones at home.
believe that Alzheimer’s disease is the biggest health
I care issue of my generation. More than 4.5 million
The People of Wyeth
Americans suffer today, and, as the baby boomer
generation ages, it is expected that this number will ur Company has exhibited a track record of
O
grow substantially. Add to that millions more affected consistency, performance and responsibility.
by the disease – the families and caregivers of Alzheimer’s The people of Wyeth know that to continue
patients – and the billions of dollars in health care costs on this path, we must maintain a relentless focus
borne by society, and the nature of the challenge and on improving our Company and running it even more
the critical importance of doing everything we can to efficiently. Our people understand that we have an
overcome it become clear. Clinical research in this field imperative to change Wyeth fundamentally in order
is complex and expensive with outcomes uncertain, to succeed in the years ahead. At its core, this effort is
but the impact of success would be enormous. based on two simple ideas. First, every year we will
We’re proud that Wyeth is at the cutting edge in aim to grow our revenue through the quality of our
seeking new drugs not only to treat Alzheimer’s disease products and their value to the people we serve. And
symptoms better than currently available therapies but second, every year we will aim to grow our profit at
potentially to stop or even reverse the course of this a faster rate than our revenue by running our Company
crippling and ultimately fatal disease. Our goal is to turn more efficiently and productively. These goals drive
the corner on this terrible illness and provide new hope. our results and determine how they are evaluated and
how we plan to improve upon them in the future.
Wyeth Research and Development Expenses Wyeth’s New Product Pipeline
($ in billions)
2001: 49 projects 2006: 77 projects
’06 3.11
LCM
2.75
’05 LCM 22%
NME 45%
’04 55%
2.46
NME
78%
’03 2.09
NME = New molecular entity
LCM = Life cycle management
5
8. Changes in Management valued at $160 million, to 250,000 Americans who
were without adequate prescription drug coverage or
am pleased that we have continued to strengthen the
I insurance. Outside the United States, we worked to sup-
leadership of our organization in a variety of ways.
port maternal health care, ensure access to reproductive
In October 2006, we welcomed Raymond J. McGuire
and child health resources, and develop a new treatment
to our Company’s Board of Directors. Mr. McGuire is
option for river blindness. We are working with the
a Managing Director and Co-Head, Global Investment
Global Alliance for Vaccines and Immunization to find
Banking, for Citigroup Global Markets Inc. I know he
an affordable and sustainable way to bring vaccines to
will provide important perspectives on our business oper-
children in the developing world. We also are working
ations and strategy. In January 2007, Bernard Poussot
hard to help protect and enrich the environment in
was elected Chief Oper-
the communities where we live and work by steadily
ating Officer of Wyeth
reducing environmental emissions and ensuring the
and joined the Com-
safety of employees at all of our facilities.
pany’s Board of Direc-
tors. Earlier in 2006, he
Looking to the Future
was promoted to Presi-
dent and Vice Chairman s we look to the future, we know that we will
A
of Wyeth. In his more be operating in a tough environment around
than 20 years with our the world. To compete, we will continue
Company, Mr. Poussot’s to attract, retain and engage a diverse workforce that
leadership has helped us broadens our perspectives, enhances our customer
transform our organiza- connections and increases our creativity. The more pro-
tion and set it on a ductive and innovative we are in our operations, the
course for continual better we will be in addressing concerns about pricing
growth. Also in 2006, and access to our medicines.
Kenneth J. Martin was We have made important progress in a relatively short
promoted to Chief time as part of a longer-term effort to find new and more
Kenneth J. Martin, Chief Financial
Financial Officer and efficient ways to meet the challenges of the 21st century.
Officer and Vice Chairman, left, and
Vice Chairman of The momentum we now have can be accelerated. We
Bernard Poussot, President, Chief
Wyeth. In addition to will continue to foster a high-performance culture where
Operating Officer and Vice Chairman.
heading our finance every person has a role, every person takes responsibility
organization, Mr. Martin took on responsibility for our and every person acts to make a difference. We will
infrastructure initiative, which is critical to our operating continue to execute against aggressive plans and develop
efficiency and, therefore, to our future success. Further systems to help ensure both success and compliance with
supporting our management team, Joseph M. Mahady the highest legal and ethical standards around the world.
was named President – Global Business for Wyeth Phar- And we will foster innovation through our creativity,
maceuticals and continues as a Senior Vice President of challenging what we do every day and seeking improve-
Wyeth. In his new role, Mr. Mahady assumes operational ments and opportunities for the years ahead. Our goal,
responsibility for Wyeth’s global pharmaceutical business. over the next decade, is to make Wyeth a stronger
With this expanded responsibility, I am certain he will company with an even higher value portfolio of prod-
bring significant insights to our worldwide business and ucts to fuel growth.
commercial portfolio. In addition, Geno J. Germano was I want to take this opportunity to thank the people
named President and General Manager, Wyeth Pharma- of Wyeth for making a difference for our Company
ceuticals – United States and Wyeth Pharmaceutical and those we serve. Thanks to their efforts, our growth
Business Unit. Robert E. Landry, Jr., was elected Treasurer has accelerated, our pipeline never has been stronger and
of Wyeth. we are on the path to deliver important new medicines
to a world in great need.
Corporate Social Responsibility
yeth recognizes its significant responsibilities
W as a global corporate citizen. One of the most
Robert Essner
important actions we can take in this regard
Chairman and Chief Executive Officer
is to expand access to our medicines. Our patient assis-
February 26, 2007
tance programs in 2006 provided free Wyeth medicines,
6
9. Wyeth’s Pipeline for Innovation
Since 2004, Wyeth has submitted 11 New Drug Applications (NDA) in the United States, delivering on our goal of
filing two NDAs for new molecular entities a year. And, over the past six years, 75 new drug candidates were placed
into development, the majority having potential to be first- or best-in-class therapies. This chart presents a snap-
shot of new drugs from Wyeth that currently are in human trials or are being reviewed by regulatory agencies.
Phase 3
Phase 2
Regulatory
Review
Phase 2
Phase 3
Regulatory
Review
Women’s Health and Bone Vaccines and
Infectious Disease
Lybrel (levonorgestrel/EE)
™
Continuous contraception 13-valent pneumococcal conjugate vaccine
Premenstrual dysphoric disorder Prevention of pneumococcal disease in
Pristiq™ (desvenlafaxine succinate) infants and children 6 months to 2 years
Vasomotor symptoms of menopause Prevention of pneumococcal disease in
Viviant™ (bazedoxifene) high-risk individuals and adults > 50
Postmenopausal osteoporosis prevention Tygacil® (tigecycline)
Postmenopausal osteoporosis treatment Community-acquired pneumonia
Aprela™ (bazedoxifene/conjugated estrogens) Hospital-acquired pneumonia
Postmenopausal osteoporosis Resistant pathogens
Vasomotor symptoms of menopause HCV-796
Dibotermin alfa (rhBMP-2) injectable Hepatitis C
Closed fractures Meningococcal B vaccine
Prevention of meningococcal disease in
Neuroscience adolescents
Bifeprunox
Inflammatory Disease
Schizophrenia (U.S.)
Bipolar disorder TRU-015
Effexor XR® (venlafaxine HCl) Rheumatoid arthritis
Major depressive disorder (Japan)
Pristiq™ (desvenlafaxine succinate) Oncology/Immunology/
Major depressive disorder
Hemophilia
Fibromyalgia
BeneFIX® (coagulation factor IX –
Neuropathic pain
recombinant)
Bapineuzumab (AAB-001)
Reformulation – hemophilia B
Alzheimer’s disease
Mylotarg® (gemtuzumab ozogamicin)
Lecozotan (SRA-333)
Relapsed acute myeloid leukemia (EU)
Mild to moderate symptoms of
Torisel™ (temsirolimus)
Alzheimer’s disease
Renal cell carcinoma
Vabicaserin (SCA-136)
Mantle cell lymphoma
Schizophrenia
Rapamune® (sirolimus)
Conversion in liver transplant
Gastrointestinal/Metabolic
ReFacto® AF (antihemophilic factor –
Protonix ® (pantoprazole sodium) recombinant)
Adult granules formulation Hemophilia A
Methylnaltrexone Bosutinib (SKI-606)
Subcutaneous for opioid-induced Breast cancer, chronic myeloid leukemia,
constipation in advanced medical illness pancreatic cancer, non-small cell
I.V. for post-operative ileus lung cancer
Oral for opioid-induced constipation HKI-272
PPM-204 Breast cancer, non-small cell lung cancer
Type 2 diabetes
Phase 2 Phase 3 Regulatory Review
Determination of safe Determination of overall Evaluation of safety
and effective dosage for benefit/risk ratio for an and efficacy data
an experimental medi- experimental medicine, by governmental
cine, generally conducted generally conducted in regulatory agencies
in hundreds of patients thousands of patients
7
10. Positioned for Growth:
An Expanding and Promising Near-Term Pipeline
Important New Drugs Projected for Filing through 2007
Women’s Health Care
A
t Wyeth, many
important new
Viviant Aprela
drugs have (bazedoxifene) (bazedoxifene/conjugated estrogens)
been filed with regulatory Viviant, a selective estrogen receptor During 2007, Wyeth is planning to
authorities or are in late- modulator, is undergoing regulatory file an NDA for Aprela for the treat-
review for the prevention of post- ment of vasomotor symptoms and
stage clinical development, menopausal osteoporosis while vaginal atrophy and for the preven-
encompassing treatments continuing in Phase 3 clinical trials tion of osteoporosis, three major
for the treatment of postmenopausal complications of menopause. Aprela
that span a variety of
osteoporosis. The National Osteo- represents the first Tissue Selective
therapeutic areas, including porosis Foundation estimates that Estrogen Complex product and
approximately 8 million women in seeks to provide the most compre-
women’s health care,
the United States hensive therapy
neuroscience, cancer and have osteoporosis for menopause
and another 22 mil- as well as a
infectious disease.
lion are at risk for new paradigm
. developing this for treatment
disease. Each year, of osteoporosis.
osteoporotic frac- The addition
tures cost the coun- of conjugated
try’s health care estrogens to
system an estimated bazedoxifene
$18 billion. for the relief of
In August 2006, a wide range
the U.S. Food and of menopausal
Drug Administration symptoms
(FDA) accepted the (including hot
Viviant New Drug flushes) is
Application (NDA) expected to add
for the prevention significant value
of osteoporosis. In for patients,
2007, Wyeth plans potentially
to submit an additional NDA for making the bazedoxifene family a
Viviant for the treatment of osteo- comprehensive approach to treat-
porosis. If approved, Viviant will ment of postmenopausal vasomotor
represent the first new agent in symptoms and postmenopausal
its class in nearly 10 years and will osteoporosis.
provide physicians with a new
option for patients at risk of osteo-
porosis and fracture.
8
11. Pristiq Lybrel
(desvenlafaxine succinate) (levonorgestrel/ethinyl
estradiol tablets)
Pristiq, a serotonin-norepinephrine
reuptake inhibitor, is being developed Lybrel is an investigational oral
with a specific focus on women. contraceptive that contains a
The product will have two indica- well-studied combination of low-
tions: the treatment of major dose levonorgestrel and ethinyl
depressive disorder and the relief estradiol.
Pristiq also has
of moderate to severe vasomotor If approved,
been studied for the
symptoms associated with it is expected
treatment of hot
menopause. to be the
flushes associated with
Pristiq is expected to improve only combi-
menopause, and
the balance of serotonin and norepi- nation oral
marketing applications
nephrine relative to that provided contraceptive
for this use were filed
by serotonin reuptake inhibitors indicated for
with the FDA and the
because of its pharmacologic profile continuous
European Medicines
as a dual reuptake inhibitor. This usage, 365
Agency in 2006. If
balance is thought to be important days a year,
approved, Pristiq
in depressed women who, when without a
will be the first non-
transitioning through menopause, placebo phase
hormonal treatment
often experience a fluctuation or or a pill-free
indicated for the
decline in estrogen that may directly interval.
relief of vasomotor
or indirectly diminish both serotonin This product,
symptoms.
and norepinephrine functioning. when taken
Additional clinical consistently,
trials now are under is designed to
way to evaluate the effectiveness make it possible for many women
and safety of Pristiq as a treatment to eliminate the bleeding associated
for fibromyalgia syndrome and with the menstrual cycle while pro-
diabetic neuropathic pain. NDA viding effective contraception. In the
filings for these two indications United States, an approvable letter
may occur as early as 2009. for Lybrel was received from the
FDA in June 2006, and, in the Euro-
pean Union, the marketing applica-
tion for Lybrel, under the trade
name Anya, also is being reviewed.
9
12. Neuroscience Cancer
Torisel
Bifeprunox leukemia (CML). CML accounts for
(temsirolimus) between 15 percent and 20 percent
of all adult leukemia cases in West-
An NDA for bifeprunox for the
Torisel is a specific inhibitor of
ern populations.
treatment of schizophrenia was
mTOR (mammalian target of
submitted to the FDA in October
rapamycin), a signaling protein that
2006. Wyeth co-develops and co-
regulates cell growth and new blood
promotes bifeprunox in the United
vessel formation. U.S. and EU filings
States, Canada and Mexico with
for Torisel were submitted in Octo-
Solvay Pharmaceuticals.
ber 2006. It is undergoing priority
The safety data for bifeprunox
U.S. regulatory review and received
consistently have shown a favorable
fast track status for the treatment of
weight and metabolic profile in
advanced renal cell carcinoma
both short- and long-term studies.
(RCC). Torisel currently is in clini-
Weight gain is a common and
cal trials for several other cancers,
serious side effect of older atypical
including mantle cell lymphoma.
antipsychotics and can cause
RCC accounts for about 85 per-
patients to stop taking their medica-
cent of all renal cancers. Patients
tion. While bifeprunox has been
with the most advanced form of the
shown to have a smaller mean effect
disease have a five-year survival rate
in acute psychosis when compared
of less than 20 percent. Recently,
with older atypical antipsychotics,
Wyeth reported data showing that
HKI-272, also in Phase 2, is a cell
it may be especially useful in
patients who were treated with tem-
signaling inhibitor that focuses on
stabilized patients who need to be
sirolimus alone experienced a 49
inhibiting tumor cell growth. This
maintained on therapy over the
percent increase in median overall
agent targets a specific growth fac-
long term because of its favorable
survival time compared with
tor receptor signaling molecule,
metabolic profile.
patients treated with interferon-
HER-2, which is found on the sur-
alpha alone. In addition to improv-
face of some breast cancer cells. It is
ing overall survival, Torisel
being studied in advanced breast
preserved a patient’s quality of life,
cancer patients who have failed
potentially helping treated patients
standard therapy. Early clinical
live longer and feel better.
data from these very early and very
small trials show encouraging
Other Oncology Compounds
patient responses, including shrink-
in Development
age of breast and lung tumors.
CMC-544 or inotuzumab,
Wyeth’s pipeline contains several
currently in Phase 1, is using a novel
innovative cancer compounds that
approach called antibody-targeted
are in the middle stages of develop-
chemotherapy. Mylotarg, also from
ment and are expected to advance to
Wyeth, uses similar technology
larger clinical trials.
and currently is indicated for the
SKI-606 or bosutinib, currently in
treatment of acute myelogenous
Phase 2, is a cell signaling inhibitor
leukemia. CMC-544 initially is
that targets critical growth path-
being developed for treatment of
ways in cancer cells that allow cells
non-Hodgkin’s lymphoma.
to divide. Clinical trial data thus far
show activity in imatinib-resistant
patients with chronic myelogenous
10
13. Gastrointestinal
Infectious Disease and Metabolic Vaccines
Methylnaltrexone
Tygacil Prevnar 13
(tigecycline) (13-valent pneumococcal
Opioid analgesics, such as mor-
conjugate vaccine)
phine, are among the most widely
Tygacil was launched on a global
used medicines to treat patients with
basis in 2005 for the treatment
Since the introduction of Prevnar
moderate to severe pain. However,
of complicated skin and abdominal
pneumococcal 7-valent conjugate
their use often results in opioid-
infections. Developed as an
vaccine in the United States, the
induced constipation or OIC, a
expanded, broad-spectrum antibi-
Centers for Disease Control and
common and serious side effect that
otic for patients with acute infec-
Prevention estimates that invasive
can be a barrier to effective pain
tions who are admitted to a
pneumococcal disease (IPD)
management. The constipation can
hospital, it offers a high likelihood
addressed by the Prevnar serotypes
be severe enough to require tempo-
of effective treatment when the
has been reduced 94 percent in
rary discontinuation of the needed
pathogen causing an infection is
children and 55 percent in adults.
opioids – thus leaving the patient
unknown and, more important,
In addition, the rate of antibiotic-
with inadequate pain relief – or
when certain resistant pathogens
resistant IPD has decreased substan-
surgical intervention. Every year, an
are suspected.
tially in infants and young children
estimated 5 million patients suffer
Tygacil also was developed to
and in adults over age 65.
from OIC in the United States alone.
combat gram-positive resistant
There currently is no approved
bacteria, including resistant Staphy-
medication that specifically targets
lococcus aureus, and gram-negative
the cause of OIC without interfering
bacteria, including ESBL-producing
with pain relief.
Klebsiella pneumoniae. It represents
Methylnaltrexone is a selective
a new weapon in the global battle
opioid antagonist being studied as
against antibiotic resistance.
a treatment to block the peripheral
Wyeth is targeting an NDA
side effects of opioid analgesics.
filing for Tygacil in 2007 to include
The drug is designed to reverse OIC
community-acquired pneumonia,
rapidly and consistently without
hospital-acquired pneumonia and
reversing analgesic effects or
additional evidence of effectiveness
inducing withdrawal symptoms.
in the treatment of infections caused
Methylnaltrexone is being
by certain atypical pathogens.
developed in subcutaneous and oral
Hospital-acquired pneumonias are
dosage forms as first-in-class treat-
of particular importance because
Building on this significant
ment platforms for OIC. It also is
of the relatively high rate of morbid-
advance in public health, Wyeth is
being developed in an intravenous
ity and mortality associated with
developing Prevnar 13, a 13-valent
(I.V.) form for post-operative ileus,
this condition. In addition, resistant
pneumococcal conjugate vaccine that
a potentially serious impairment of
organisms are becoming more
targets 13 strains of S. pneumoniae.
gastrointestinal function that can
prevalent in pneumonia, further
This new vaccine currently is under-
delay surgical recovery and prolong
increasing the risk of mortality.
going worldwide Phase 3 trials in
hospitalization.
both children and adults, with regu-
Wyeth is developing methylnal-
latory submissions expected to begin
trexone in collaboration with
in 2009. If approved, Prevnar 13
Progenics Pharmaceuticals, Inc. The
would be the most complete vaccine
companies plan to submit NDAs
available for the prevention of pneu-
for subcutaneous methylnaltrexone
mococcal disease and otitis media in
in early 2007, I.V. methylnaltrexone
young children. For adults, Prevnar
in late 2007 or in early 2008 and
13 is expected to extend protection to
oral methylnaltrexone in late 2008
persons age 50 and older and to pro-
or early 2009.
vide them with long-term protection.
11
14. THE
WAR on Alzheimer’s
“ ach morning, for more years than I wish to caregivers are added to the toll. Treatments cost
E remember,” says Meryl Comer, a 62-year- the U.S. health care system more than $100 billion
old award-winning broadcast journalist, annually. In the next 20 years, the number of
“I reintroduce myself to my husband, Harvey. victims will increase sharply, with the potential to
I say, ‘Good morning, love. My name is Meryl. bankrupt our health care system. “There are no
I am your wife. We’ve been married for 25 years. cures, no remissions,” says former Speaker of
Don’t worry. This is your home. And you are the U.S. House of Representatives and Center for
safe.’ His eyes are blank, and mine fill with tears.” Health Transformation founder Newt Gingrich.
Dr. Harvey Gralnick, once a leading researcher “You won’t meet an Alzheimer’s survivor because
at the National Institutes of Health, has had there are none. The need for medical break-
Alzheimer’s disease for 12 years. Meryl, his throughs never has been greater.”
caregiver, has been suffering for just as long. Wyeth is on the leading edge of potential
Dr. Gralnick is among 4.5 million Americans breakthroughs, having declared an all-out war
with Alzheimer’s disease. In the United States, it on the disease. This special report introduces
strikes one of every 10 people over age 65 and the faces of Alzheimer’s, the weapons being
nearly half of those over age 85. About 18 million developed and the battles that still need to be
people suffer worldwide – millions more when waged – and won.
12
16. Understanding the Enemy
A Primer on Alzheimer’s Disease
ne hundred years on ways to inhibit tangles,
O after Alois though many scientists
Alzheimer, a now believe that these
German psychiatrist and form later in the disease
neuropathologist, first process – perhaps driven
characterized the plaques by the amyloid deposition.
and tangles in the autop- Symptoms of
sied brain of a victim Alzheimer’s disease
of this crippling and ulti- include loss of memory –
mately fatal degenerative first short term and
disease, researchers eventually the ability to
still are not fully certain remember the past or
what causes Alzheimer’s create new memories;
This photomicrograph shows the outermost layer of the brain of
or exactly what the right difficulty in speaking and
an Alzheimer’s disease sufferer. The red-colored accumulations are
beta-amyloid plaques.
strategy is to defeat it. reading; disorientation;
“Alzheimer’s disease and, ultimately, loss of
was widely misunder- capacity to dress, bathe
secretase – cut this protein insoluble in some people
stood for many years,” or perform what com-
in certain ways, normal after six decades of being
says Sid Gilman, M.D., monly are called activities
amyloid transforms into fluid. The aggregation,
professor and Chair of of daily living. Says
beta-amyloid peptide. for whatever reason, leads
the Department of Neu- Dr. Gandy: “Over time,
It becomes sticky and to a misfolding of the
rology at the University of all of the outside surface
aggregates together in the protein. And once it takes
Michigan and Director of of the brain, all of the
brain. Eventually, these shape as what basically is
the Michigan Alzheimer’s cerebral cortex – the part
aggregates accumulate a bobby-pin-like structure,
Disease Research Center that’s responsible for
between the nerve cells in it becomes locked in that
there. “As people aged, thinking – degenerates,
parts of the brain respon- structure and accumulates,
it was widely believed and patients die bed-
sible for memory and forming amyloid plaques.
that they simply lost their bound in a vegetative
judgment. As that happens, you see
memory. Today, some state.”
Samuel Gandy, M.D., the characteristic lesions of
physicians still think Joel Ross, M.D., has
Ph.D., Chair of the Alzheimer’s disease.”
memory loss is normal as been a practicing geriatri-
National Medical The other
you grow older. That’s cian and internist for the
and Scientific abnormal pro-
not so. You should retain past 20 years and has seen
Advisory tein that
your memory until you some 1,000 Alzheimer’s
Council of the appears in
die. Alzheimer’s is a dis- patients during that time.
Alzheimer’s the disease is
ease process, and aging is “Anger and depression
Association, called tau,
just one risk factor.” are common in early
notes, “The which accu-
What may be the disease. Psychosis is not
amyloid mulates in
primary culprit? Many unusual in later disease.
peptide nor- the cells
researchers believe it is the And the wandering we
mally is found themselves,
toxic form of a protein – sometimes see is a func-
between nerve leading to the
called amyloid precursor tion of disorientation
cells in your tangles that
protein – that appears and lack of memory.”
blood or in your Dr. Alzheimer first
naturally in small quanti-
spinal fluid. The chal- saw. The tangles develop
ties in our bodies. When
lenge is why it becomes inside the nerve cells,
two enzymes – gamma Left: This CT scan of a brain
eventually killing them. shows the atrophy caused by
secretase and beta
Some drugs are focusing Alzheimer’s disease.
14
17. “I would do anything to keep him Memory problems and confusion at his last job as a
chemical salesman contributed to his employment being
just the way he is today.” terminated in April 2005. Ted explains: “I made a lot of
my sales calls by phone, but I couldn’t remember exactly
what people had said to me after I hung up. I was taken
June and Ted Roderick: They’re a Couple
out of sales and put in other jobs. Was it fair? It’s hard
to say.”
J une and Ted Roderick are at the leading edge of the Ted finds humor a good defense mechanism. “Actu-
baby boomer generation – a time when many think ally, it’s a good excuse if I don’t want to do something
about retirement, new hobbies, vacation plans, grand- around the house. I can say, ‘I forgot.’ They’re the
children. But June and Ted are too preoccupied for two words I use most.” But sometimes it’s hard. “June
that. Ted, age 63, has Alzheimer’s disease and has had will arrive home and ask what I did during the day.
it for at least six years. I know I did things, but I don’t know what they were.
“We’re fortunate because Ted continues to function It’s frustrating.”
at a high level,” his wife June says. “He’s still driving June says, “You take every day and appreciate what
and can read short articles in the newspapers and you have. I would do anything to keep him just the
magazines.” way he is today. We’ve been married 40 years. I hope
Ted also can take apart a faucet and put it back we can continue the way we are.
together and make screens for storm windows. He says, “We worry about losing each other,” she adds. “That’s
“I feel more competent doing mechanical tasks than why we keep fighting and trying to do everything we
mental things. I just forget stuff.” And he speaks ration- can to prevent the disease from getting worse. We won’t
ally about his disease. “I can’t remember what I did stop. We do everything together. You see, we’re a couple.
an hour ago or yesterday. It’s annoying, but, for now, And we want to stay a couple.”
it’s not debilitating.”
15
18. William Utermohlen,
an American artist
living in London, chron-
icled the progression
of his Alzheimer’s
disease in a series of
self-portraits, several
Changes in personality Dr. Gandy says, a series of biomarkers,
of which are shown
also can include anxiety “the medicines or proteins, whose pres-
here. The top painting,
and apathy or even suspi- we have today ence in the blood or spinal
completed shortly after
he learned he had the
ciousness, agitation or wear off and fluid may indicate the
disease, is followed by
delusion. With the passing aren’t effective. disease already is at work.
others he created as
of time, victims may lose They don’t “I would advocate
the disease pro-
their ability to swallow appreciably slow starting a therapy when
gressed and affected
his abilities and per-
and eat solid foods or the progression amyloid is just beginning
ceptions. Today, Mr.
become incontinent. of the disease to be deposited – before
Utermohlen resides in
Often they die from the and don’t attack significant symptoms
a nursing home and
consequences of being the underlying occur,” adds Ronald Black,
no longer paints.
bedridden or sustaining pathology.” M.D., Senior Director,
a physical injury, like a Most researchers Neuroscience Clinical
broken hip. Many don’t now believe Development at Wyeth.
at risk factors
recover, in part, because toxic amyloid “That is the promise
and treat at least a
they can’t remember they and tau begin of prevention. It parallels
decade in advance
are sick or had an accident forming years treatment of breast
of cognitive decline.
and can’t understand before symptoms cancer: Detect and treat
The reason for
directions for therapies appear. So even at an early stage.”
that length of time
to help them get better. as researchers Wyeth is participating
is because Mother
“We believe there is begin to seek in the Alzheimer’s Disease
Nature is very
a genetic basis for this new treatments Neuroimaging Initiative,
careful. There is so
disease,” says Dr. Gilman. for Alzheimer’s, a five-year public/private
much redundancy
Having the gene called they are focusing partnership that has
in the brain that
Apolipoprotein E4 puts on how to diag- brought together industry,
one has to lose
one at greatest risk, often nose the disease academia and the National
huge numbers of
predisposing a person to at its earliest Institutes of Health to
nerve cells before
develop the disease sooner possible stages. validate biomarkers and
symptoms develop.”
rather than later. “If you The basic principle, develop new neuroimag-
Standard psychologi-
look at the universe of Dr. Gandy notes, “is to ing tools.
cal testing, coupled with
Alzheimer’s patients,” he target the disease before How do physicians
imaging, is about 80 per-
adds, “50 percent have permanent damage help patients when so few
cent to 90 percent accurate
the ApoE4 gene.” to neurons occurs. Part therapies are available?
in diagnosing the disease
Included among of the reason to target Among other things,
and staging it – from mild
known physical aspects amyloid is that it is felt “We encourage them to
to moderate to severe.
of the disease is the loss to accumulate early in participate in our clinical
Diagnosis also includes
of nerve cells that use the the disease cascade. Once trials for their own sake
ruling out other possible
neurotransmitter acetyl- there is an effective ther- and for the sake of others
physical or psychological
choline, a chemical that apy that treats early stages afflicted with this devastat-
causes that may be more
these cells use to commu- of the disease, the field ing disease,” Dr. Gilman
treatable, such as severe
nicate with each other. will try to identify patients says. “I tell them what
depression, alcoholism,
Nearly all the currently earlier and earlier. We they can expect next.
thyroid malfunction,
approved medicines target hope this information will I prepare them as best I
brain traumas or stroke.
this aspect of the disease. lead to prevention of can. At least today, we
Scientists are making
However, as Alzheimer’s Alzheimer’s by identifying have great hope for better
progress toward develop-
progresses and nerve patients most at risk.” treatments – more than
ing simpler tests for the
cells become impaired to Dr. Gilman agrees: ever before. This is the
disease by identifying
the point of degenerating, “It would be ideal to look dawn of a new age.”
16