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wyeth 2006 Analysts Meeting Presentation
1.
2. Welcome
Justin R. Victoria
Vice President, Investor Relations
3. Forward Looking Statement
The statements in these materials that are not historical facts are forward-
looking statements based on current expectations of future events and are
subject to risks and uncertainties that could cause actual results to differ
materially from those expressed or implied by such statements. These risks
and uncertainties include risks associated with the inherent uncertainty of
the timing and success of product research, development and
commercialization (including with respect to our pipeline products), drug
pricing and payment for our products by government and third-party payers,
manufacturing, data generated on the safety and efficacy of our products,
economic conditions including interest and currency exchange rate
fluctuations, changes in generally accepted accounting principles, the
impact of competitive or generic products, trade buying patterns, global
business operations, product liability and other types of litigation, the
impact of legislation and regulatory compliance, intellectual property rights
including the ability of any particular patent to provide market exclusivity,
strategic relationships with third parties, environmental liabilities, and other
risks and uncertainties, including those detailed from time to time in our
periodic reports filed with the Securities and Exchange Commission,
including our current reports on Form 8-K, quarterly reports on Form 10-Q
and annual report on Form 10-K, particularly the discussion under the
caption “Item 1A, Risk Factors.” We assume no obligation to publicly
update any forward-looking statements, whether as a result of new
information, future developments or otherwise.
4. Agenda
J. Victoria
Welcome
R. Essner
Introduction
U. Wiinberg
Enbrel® & Prevnar®
E.A. Emini, Ph.D.
Prevnar 13
Break
J.M. Mahady
New Products
G. Constantine, M.D.
Pristiq™
Aprela™/Viviant™
Lybrel™
J.S. Camardo, M.D.
Torisel™
Tygacil®
R.M. Poole, M.D., FACP
Bifeprunox
J.S. Camardo, M.D.
Methylnaltrexone
R.R. Ruffolo, Jr., Ph.D.
Mid-Pipeline Review
Key Registration Submissions
B. Poussot
Conclusion & Q&A
5. Introduction
Robert Essner
Chairman and Chief Executive Officer, Wyeth
13. Enbrel® 2005
Over 376,000 Patients Treated Worldwide
EMEA
$958
North America*
$2,574
$3,658
2005 Worldwide Sales
Asia Pac
$79
Latin America
$46
$ in Millions
*Alliance with Amgen
15. Enbrel® Momentum
2005 Actual
Region ($ in Millions) % Growth
EMEA $958 52%
Latin America $46 64%
AP/Japan* $79 295%
Total Regional
Net Sales $1,083 59%
*Japan Launch March 2005
16. Enbrel®
Growing From a Position of Strength
Anti-TNF Biologic Sales – Ex-North America ($000)
Quarterly Sales
$400,000
Enbrel Remicade Humira Orencia Raptiva
$350,000
$300,000
$250,000
$200,000
$150,000
$100,000
$50,000
$0
Q1'04 Q2'04 Q3'04 Q4'04 Q1'05 Q2'05 Q3'05 Q4'05 Q1'06 Q2'06
IMS, Midas Q2 2006
17. Enbrel® -- $3 Billion in 2010
Outside North America
Market Factors
Large available patient pool
Doctors & payers inclined to early
intervention with Enbrel
Enbrel
Geographic and medical expansion
Unique mechanism of action with extensive
safety/efficacy
Patent protection through 2014
18. Available Patient Pool:
Top 6 EU Countries
Prevalence of Disease
RA AS PsA PsO
1.8 Million 1.3 Million 826,000 6.0 Million
Guidelines for Eligibility
Current Biologic Patients
360,000 Patients
19. Japan Opportunity
Japan
1 in 10 Currently Treated
140
Incremental Opportunity
120
# Patients (2005)
Number of Patients (000’s)
6
100
80 ~60,000
60
110
40 49
20 28
13
4
0
Bio-Potential (M) Biologics(M) Enbrel(M)
SOURCE: Wyeth Forecasting; C&MI
NOTE: Slide depicts RA, PsA, AS and Psoriasis
20. Enbrel® Science
14 Years Experience
#1 biologic prescribed worldwide in its class
Approaching 1 million patient years of use
Studied in patients 4 to 87 years of age
Serious adverse event profile similar to placebo
in clinical trials
Unique mechanism of action
21. Enbrel® Science
14 Years of Clinical Experience
Percentage of Early RA Patients
With No Radiographic Progression
5 Years
Sustained
73%
NO further joint space narrowing
NO further joint space narrowing
Efficacy
After 5 years
64%
NO new erosions
NO new erosions
NO progression in
55%
NO progression in
Total Sharp Score
Total Sharp Score
n = 100
Genovese MC, Bathon JM, Fleischmann RM, et al. Longterm safety, efficacy, and radiographic outcome with etanercept
treatment in patients with early rheumatoid arthritis. J Rheumotol 2005;32:1232-1242.
22. Trend Towards Earlier Treatment
Recent- Severely-
Moderately-
Onset RA Advanced RA
Advanced
RA
23. Value: Favorable Cost-Benefit
NICE Guidance 2006
The National Institute for Health and Clinical
Excellence (NICE, UK) recommends the use of
ENBREL® for the treatment of plaque
psoriasis BEFORE the use of Raptiva
ENBREL had a more favorable economic
profile in the treatment of patients with
psoriatic arthritis than Remicade
24. Convenience
Pre-filled Syringe 25mg/50mg
Autoinjector
Patient Services
NEW!
The flexibility of 3 administration options
25. Enbrel® Growth-2010
Wyeth-Only Territories – 24% CAGR
2005 2010
$1 Billion $3 Billion
Asia Asia
Latin Pacific Pacific
America $79 15%
Latin
$46
America
5%
Europe Europe
Europe Europe
$958 80%
$958 80%
$ in Millions % of Revenue by Region
26. Grange Castle … Wyeth’s Commitment
to Biotech Growth
4 Integrated
Manufacturing Facilities
Drug Substance
Vaccine Conjugation
Fill / Finish
Syringe Line
MNTX
28. Prevnar® – Strong Growth Momentum
June 2006 YTD Δ vs 1H05
Region
North America $565 million +13%
EMEA $285 million +94%
Latin America $45 million +70%
Asia Pacific $55 million +41%
TOTAL $950 million +33%
29. Global Vaccine Sales by Product
2005 Audited Sales
1st and Only Blockbuster Vaccine
$1,200
Prevnar®
$1,000
Audited Annual Sales ($MM)
$800
Varivax
Combined
audited sales
$600
Engerix B
of these four
vaccine products
MMRII
$400
does not equal
Prevnar’s sales
Vaxigrip
$200
$0
Source: IMS MIDAS Data, ATC2-J7, April 2006.
30. Growing Prevnar® to $3 Billion in 2010
Accelerating momentum in 2006
New launches
New national immunization programs in developed
markets
Emerging countries – private and national programs
Increased compliance and catch-up opportunities
$3 Billion Prevnar Sales
(Infant Vaccination)
32. The Face of
Pneumococcal Disease
.5M
Adults die
every year
1M
Infants die
every year
33. Disease Burden in Children
DTP/Polio
S. Pneumo
20%
28%
Measles
Hib
21%
15%
Rotavirus
15%
Other
1%
#1 Cause of
Vaccine-Preventable Death in Children
WHO 2004 Global Immunization Data
34. Impact on
Pneumococcal Disease
Since the launch
of Prevnar ® …
Tens of millions of children immunized
Millions of cases of disease averted
Tens of thousands of lives saved
…many more children and adults will benefit as
we expand the use of Prevnar across the globe
35. Increasing Impact of Prevnar® in U.S.
…in children … and adults
(>50 Years of Age)
Average Incidence of Vaccine Serotype
90 35
Prelicensure Prelicensure
80 30
(1998-1999) (1998-1999)
IPD per 100,000 Population
Estimated Cases/100,000
70 Postlicensure Postlicensure
25
60 (2003) (2002-2003)
55%
20
50
40 Reduction
15
94%
30
10
Reduction
20
5
10
0 0
Average for 2003 Average for 2003
1998 and 1999 1998 and 1999
MMWR. 2005;Vol: 54(No. 36):893-897.
36. Significant Future Growth Potential
Double sales over the next 5 years
$4
$3 B +
$3 New Launches
New Launches
NIPs
NIPs
Sales ($B)
Emerging Markets
Emerging Markets
Compliance/
Compliance/
$2 Catch-up
Catch-up
$1.5 B
$1
$0
2005A 2010F
Source: Wyeth internal sales data, 2006
38. National Immunization Programs:
Developed Countries
Current NIPs Potential NIPs
United States Austria Taiwan
Australia Belgium New Zealand
Canada Denmark Portugal
France Finland Saudi Arabia
Germany Hong Kong Singapore
Greece Iceland South Korea
Luxembourg Ireland Spain
Netherlands Italy Sweden
Norway Japan
Qatar
Switzerland
United Kingdom
Total Birth Cohort ~7 Million Total Birth Cohort ~4 Million
39. Emerging Market Opportunities
Private Markets
Private to Potential NIPs
Chile Peru
Argentina
China Philippines
Brazil
Ecuador Romania
Colombia
Hungary Russia
Czech Republic
India South Africa
Mexico*
Indonesia Thailand
Poland
Malaysia Uruguay
Turkey
Pakistan
Venezuela
Total Birth Cohort ~10 Million Total Birth Cohort ~58 Million
* Mexico announced initiation of national program in 3Q06
40. Growth in NIP Countries
Increase compliance with country-recommended
regimens (U.S. example)
2002 public/private market compliance ~40%
(3 doses or more)
2005 public/private market compliance ~83%
(3 doses or more)
Target DTaP “Gold Standard” compliance ~90%
Each compliance % point increase ~$10 million/year
Catch-up opportunities
U.K. program 1.7 million doses in 2006/2007
41. Growing Prevnar® to $3 Billion in 2010
Accelerating momentum in 2006
New launches
New national immunization programs in developed
markets
Emerging countries – private and national programs
Increased compliance and catch-up opportunities
$3 Billion Prevnar Sales
(Infant Vaccination)
42. The Future of
Pneumococcal Vaccines:
Leading the Way Toward
Extended Serotype Coverage With
Pneumococcal 13-Valent Conjugate Vaccine
New advances in vaccine development
Potential 10 valent competitive candidate
Prevnar 13 in Phase 3 development
Increase pneumococcal serotype coverage
(13 serotypes)
Expand use to adults (> $1.5 billion)
43. 13-Valent Pneumococcal Polysaccharide
Conjugate Vaccine
(13v PnC)
Emilio A. Emini, Ph.D., F.A.A.M.
Executive Vice President
Vaccine Research and Development
44. 13v PnC Infant Product Profile
The most complete vaccine available for the
global prevention of pneumococcal disease
and otitis media
Phase 2 proof of concept achieved
Licensing criteria agreed upon
Status Worldwide phase 3 studies
ongoing
Submission – Early 2009
Peak Sales > $3 Billion
45. 13v PnC Provides
Superior Coverage in the U.S.
7v vs 10v vs 13v Serotype Coverage Comparison – U.S.
7v
Pre-Prevnar® (1998) 81%
Source: CDC ABC Surveillance
46. Estimated Invasive Pneumococcal Disease Rates
Due to Vaccine Serotypes
(Children <5 Years of Age)
90
Estimated Cases/100,000
Prelicensure
80
(1998-1999)
70
Postlicensure
60
(2003)
50
94%
40
Reduction
30
20
10
0
Average for 1998 and 2003
1999
Active Bacterial Core Surveillance, Emerging Infections Program Network. Prevnar® was licensed in the
United States in February 2000.
47. Estimated Invasive Pneumococcal Disease Rates
For All Serotypes
(Children <5 Years of Age)
120
Estimated Cases/100,000
Prelicensure
100 (1998-1999)
Postlicensure
80
(2003)
60
75%
Reduction
40
20
0
Average for 1998 and 2003
1999
Active Bacterial Core Surveillance, Emerging Infections Program Network. Prevnar® was licensed in the
United States in February 2000.
48. 13v PnC Provides
Superior Coverage in the U.S.
7v vs 10v vs 13v Serotype Coverage Comparison – U.S.
7v
Pre-Prevnar® (1998) 81%
Post-Prevnar (2003) 17%
Prevnar has greatly reduced serious disease caused by the
7 vaccine-associated serotypes
Source: CDC ABC Surveillance
49. 13v PnC Provides
Superior Coverage in the U.S.
7v vs 10v vs 13v Serotype Coverage Comparison – U.S.
7v 10v
Pre-Prevnar® (1998) 81%
Post-Prevnar (2003) 17% 22%
Prevnar has greatly reduced serious disease caused by the
7 vaccine-associated serotypes
A 10v vaccine provides only marginal additional coverage
Source: CDC ABC Surveillance
50. 13v PnC Provides
Superior Coverage in the U.S.
7v vs 10v vs 13v Serotype Coverage Comparison – U.S.
7v 10v 13v
Pre-Prevnar® (1998) 81%
Post-Prevnar (2003) 17% 22% 60%
Prevnar has greatly reduced serious disease caused by the
7 vaccine-associated serotypes
A 10v vaccine provides only marginal additional coverage
13v PnC will provide substantial coverage
Source: CDC ABC Surveillance
51. 13v PnC Also Provides Superior
Coverage in Other Countries
7v vs 10v vs 13v Serotype Coverage Comparison
7v 10v 13v
France pp 44% 49% 70%
Germany pp 52% 68% 81%
Spain pp 31% 48% 83%
Norway 63% 67% 83%
Mexico 53% 59% 74%
pp = Post-Prevnar®
54. Incidence of Invasive Pneumococcal
Disease Due to Serotype 19A in the U.S.
(Children <5 Years of Age)
7
Rate (Cases/100,000 Population)
6
5
4
3
2
1
0
July 1999 – July 2000 – July 2001 – July 2002 – July 2003 –
June 2000 June 2001 June 2002 June 2003 June 2004
Time
Pai R. JID. 2005;192:1988-95.
55. Comparison of Prevnar® and 13v PnC in a Phase 2 Infant Trial:
Percentage of Children Achieving a Protective Level of Functional
Antibody Following the Primary Immunization Series
100
75
Percentage
50
25
0
4 6B 9V 14 18C 19F 23F 1 3 5 6A 7F 19A
Serotype
7v 13v
56. The Infant Vaccine Phase 3 Program
Objectives:
Demonstrate the immunological non-inferiority of
13v PnC to 7-valent Prevnar® in young infants
Demonstrate that 13v PnC does not interfere with
immune responses elicited by concomitantly
administered childhood vaccines
Demonstrate immunological consistency across
multiple production batches of the vaccine
Demonstrate the vaccine’s safety and tolerability
The program will involve approximately
4,000 children
57. 13v PnC Adult Product Profile
The vaccine of choice for adults 50 years
of age and older for the prevention of
pneumococcal disease
Proof of concept achieved
Licensing criteria agreed upon
Status Worldwide phase 3 clinical
studies to begin in late 2006
Submission 2009
Peak Sales > $1.5 Billion
58. The Need for an Improved
Pneumococcal Vaccine for Adults
Current vaccine is a 23-valent free polysaccharide vaccine
(23v Ps) indicated for adults 65 years and older
Antibody titers and efficacy decline after 5 years1
23v Ps induces immunological hyporesponsiveness to either
another dose of 23v Ps2 or to a dose of conjugate vaccine3
Re-vaccinations with 23v Ps cause more severe adverse
events4
Therefore, 23v Ps is generally given only once, which
provides only a narrow window of protection during a
prolonged period of risk5
Effectiveness is very low in immunocompromised patients
Shapiro, et al., NEJM 1991;
1
Torling, et al., Vaccine 2003;
2
deRoux, et al., IDSA 2005;
3
Jackson, et al., JAMA 1999; Vaccine 2005;
4
ACIP recommendation: MMWR 1997.
5
59. There Remains a Substantial Invasive Pneumococcal
Disease Burden in the U.S.
(2004 Rates With 60% Uptake of 23v Ps Vaccine)
75
Cases of Invasive Pneumococcal Disease
Cases per 100,000
50
25
0
18 to 34 35 to 49 50 to 64 65 to 79 80+
Age Group Years
Estimated # of Deaths
1800
Deaths
1200
600
0
18 to 34 35 to 49 50 to 64 65 to 79 80+
Age Group Years
CDC, ABC Surveillance 2004 (provisional)
60. 13v PnC Will Offer Additional Benefits
Over 23v Ps Vaccine
Conjugate vaccine antibody responses are
superior to 23v Ps antibody responses
Conjugate vaccine does not induce immunological
hyporesponsiveness
Therefore, 13v PnC can be used to extend the age
range of protection against pneumococcal disease
(50 years of age and older) and provide long-term
protection by repeat dosing
61. Immunological Hyporesponsiveness of
the 23-Valent Polysaccharide Vaccine
Relative Antibody Response
Immune response
depressed
after 2nd dose
Pre-dose 1 Post-dose 1 1 year Pre-dose 2 Post-dose 2
(4-7 years)
Torling, et.al (2003) Vaccine 22:96-103.
62. Randomized Trial of 7-valent Prevnar® (7v PnC) and
23v Ps Vaccine in Naïve Elderly 70+ Years of Age
Year 1 Year 2
7v PnC
7v PnC n = 43
23v Ps
n = 110
n = 38
23v Ps 7v PnC
n = 78
n = 109
63. Is the Antibody Response to 7v PnC Equivalent/
Superior to the 23v Ps Response?
Year 1 Year 2
7v PnC
7v PnC
23v Ps
23v Ps 7v PnC
64. 7v PnC Functional Antibody Response is
Equivalent or Superior to 23v Ps Response
3000
*
7v PnC 23v Ps
2500
2000
OPA GMT
*
1500
* *
1000
500
0
4 6B 9V 14 18C 19F 23F
Serotype
7v PnC n = 110
23v Ps n = 104-107
* Statistically significant
65. Does Prior 23v Ps Immunization Affect the Response
to Subsequent 7v PnC Immunization?
Year 1 Year 2
7v PnC
7v PnC
23v Ps
23v Ps 7v PnC
67. Does Prior 7v PnC Immunization Blunt the Response
to a Second Dose of 7v PnC?
Year 1 Year 2
7v PnC
7v PnC
23v Ps
23v Ps 7v PnC
68. Prior 7v PnC Does Not Blunt the Response
to a Second Dose of 7v PnC
18
7v PnC 7v PnC 7v PnC
15
EL ISA G MC (μ g /m l)
12
9
6
3
0
4 6B 9V 14 18C 19F 23F
Serotype
7v PnC n = 61
23v Ps 7v PnC n = 31
69. Does Prior 7v PnC Immunization Affect the Response
to Subsequent 23v Ps Immunization?
Year 1 Year 2
7v PnC
7v PnC
23v Ps
23v Ps 7v PnC
70. Prior 7v PnC Does Not Blunt the Response
to Subsequent 23v Ps
18
23v Ps 7v PnC 23v Ps
ELISA GMC (μg/ml)
15
12
9
6
3
0
4 6B 9V 14 18C 19F 23F
Serotype
23v Ps n = 62
7v PnC 23v Ps n = 30
71. Conclusions
Conjugate vaccine can be used repeatedly without
inducing hyporesponsiveness
Free polysaccharide vaccine can be administered
after conjugate vaccine without
hyporesponsiveness
Conjugate vaccine should be given first, if both
vaccines are used to maximize serotype coverage
72. Impact of Extending The Age Range
of Protection with 13v PnC
Preventable
Invasive Deaths
Disease Preventable/
Cases Year
23v Ps alone in the U.S. in the U.S.
2979 489
13v PnC alone
Conjugate with re-vaccination 5544 895
13v PnC + 23v Ps
6110 988
50 yr 65 yr 70 yr
73. The Adult Vaccine
Phase 3 Program
Objectives:
Demonstrate immunological non-inferiority of
13v PnC to the 23-valent polysaccharide vaccine in
vaccine-naïve adults >50 years of age
Demonstrate that 13v PnC can enhance the anti-
polysaccharide responses in adults previously
immunized with the 23-valent vaccine, and that
initial immunization with 13v PnC does not cause
immunological hyporesponsiveness
Demonstrate that 13v PnC does not interfere with
the immune response to concomitantly administered
influenzavirus vaccine
Demonstrate the vaccine’s safety and tolerability
The program will involve approximately 3,200 adults
74.
75. New Product Opportunities
Joe Mahady
Senior Vice President, Wyeth
President, Wyeth Pharmaceuticals,
The Americas and Global Businesses
76. SNRI Profile Makes Effexor XR®
the #1 Antidepressant in the World
$4,000
Zoloft
$3,000
US Sales Dollars (000s)
Lexapro
$2,000
Wellbutrin
Paxil
$1,000
Cymbalta
$0
2001 2002 2003 2004 2005 2006
Rolling MATs Ending June 2006
Source: IMS Monthly Midas (Aug 06); Constant US$ (Mil)
78. Pristiq™
Proven SNRI Pharmacological Impact for
Management of Depression
Similar to Effexor XR® in terms of
efficacy, safety and tolerability
Very low potential for drug-drug
interaction
Well-established QTc safety profile
79. Pristiq™ Differentiation
With FDA-approval, the first
non-hormonal treatment of moderate-
to-severe vasomotor symptoms (VMS)
associated with menopause
80. WHI Trial Reduced Prescription of
Hormone Products
120,000
Hormone Prescriptions (000)
New Prescriptions
100,000
Total Prescriptions
80,000
Women's Health Initiative:
Initial Results Released
60,000
40,000
20,000
0
MAT MAT MAT MAT MAT MAT MAT MAT
3/99 3/00 3/01 3/02 3/03 3/04 3/05 3/06
Source: IMS NPA Data (May 06)
81. A Small Percentage of the 23 Million Symptomatic
Women Use Available Treatments
Menopausal Women Hysterectomized Women
Experiencing Hot Flushes Experiencing Hot Flushes
10% Use 30% Use
Hormone Estrogen
Therapy Therapy
15 Million Women 8 Million Women
Sources: Wyeth /ICR Patient Study Dec 2005, projected to total population using U.S. census data
82. Pristiq™
(Desvenlafaxine Succinate)
With FDA-approval, the first
non-hormonal treatment of moderate-
to-severe vasomotor symptoms (VMS)
associated with menopause
83. Transition Through Menopause Can Be
Associated With New Onset or Recurrence
of a Major Depressive Episode
Estrogen fluctuation or decline may diminish
serotonin and norepinephrine functioning
Dual reuptake inhibitor may be a better fit
for depression associated with menopause
84. Women Represent Over 70% of Patients
Treated with an Antidepressant
Treated Patients by Gender
Female
Female
71%
<40 Years
19%
Male Female
>40 Years
29%
52%
Source: SDI Longitudinal Patient Data, April 2006 (USA)
86. Pristiq™, A Single Product With
Two Indications
Pristiq
Vasomotor Symptoms
Depression
Positioning Positioning
First Line Treatment of First FDA-Approved
Major Depressive Disorder Non-Hormonal Treatment of
Associated With Menopause Moderate-to-Severe VMS
87. Pristiq™
Pristiq
Can become the first and only SNRI proven to
effectively address the distinctive symptoms and
therapeutic needs of women with:
Depression associated with menopause
Vasomotor symptoms
Fibromyalgia
88. Providing Specific Benefits for Over
35 Million Women
U.S. Prevalence
Major Vasomotor
Depression symptoms Fibromyalgia
23 Million2 4 Million3
12 Million1
Women Women
Women
1 National Institute of Mental Health. “What To Do When A Friend is Depressed…” Bethesda (MD): National Institute of
Mental Health, National Institutes of Health, U.S. Department of Health and Human Services; 2001.
2 Wyeth /ICR Patient Study Dec 2005, projected to total population using U.S. census data
3 Patient Base by Decision Resources, August 2005
2006 Syndicated Depression Omnibus shows VMS and depression overlap of ~3M women, 2005 Depression Consumer
Landscape Study shows fibromyalgia and depression overlap of ~1M women
89. Pristiq™
(Desvenlafaxine Succinate)
Ginger Constantine, M.D.
Vice President and Therapeutic Area Director
Woman’s Health and Bone Repair
Clinical Research & Development,
Wyeth Pharmaceuticals
90. Pristiq™ Modulates Serotonin and
Norepinephrine
May be Integral in Modulation of Depression,
Thermoregulatory Dysfunction, Pain
Being Developed for
Female Predominant Conditions
Major Depression
Vasomotor Symptoms
Fibromyalgia
91. Estrogen: Complex Regulatory Effects on
Serotonin and Norepinephrine Pathways
Estrogen influences serotonin and
norepinephrine:
Neuronal firing
Release rates
Affects specific receptors
Increases synthesis and decreases breakdown
Norepinephrine stimulation of serotonin neurons
may offset estrogen loss
92. Menopause and Depression Are Linked
Postmenopause
Depressed Mood Premenopause
Irritability
0% 20% 40% 60% 80% 100%
% Women With Symptom
Maartens LW, et al Fam Pract.;18:189-94,2001.
93. Risk of Depressive Episode Greater
During Perimenopause
7
Risk of Depressive Onset (%) 6
5
4
3
2
1
0
Premenopause Perimenopause
Schmidt, et al. Am J Psychiatry. 2004.
94. Remission of Depression:
Differential Response With Age
SSRIs and SNRIs
Pooled Analysis of 32 Depression Studies
50
Placebo SSRIs* Effexor®/Effexor XR®
Remission Rate, Week 8 (%)
†‡ †‡
P≤0.05
40
†
36%
30
30%
20
10
0
<40 <40 >55 <40 >55
>55
(n=263) (n=108) (n=1041) (n=367) (n=1007) (n=355)
Age
*SSRIs=fluoxetine, fluvoxamine, paroxetine, sertraline, and citalopram.
†P≤0.05 drug vs. placebo. ‡P≤0.05 vs. SSRIs.
Younger women = age ≤40; older women = age >55.
Cohen LS, et al. Poster presented at ACNP Annual Meeting; San Juan, Puerto Rico; December 2004.
95. Pristiq™
(Desvenlafaxine Succinate)
Efficacy on Major Depressive Disorders
Men & Women
96. Pristiq™: Effective in Treating
Major Depressive Disorder
Efficacy demonstrated at:
100, 200, and 400 mg in short–term studies
200 and 400 mg in a 6-month relapse
prevention study
105. The Majority of Women
Will Suffer Hot Flushes
70
Hot Flush
60
50
% of Women
40
30
20
10
0
38 44 46 50 52 54 56 58 60 62 66 72
Age in Years
Source: Rodstrom K. et al. Menopause 2002 9(3): 156-161
106. Pristiq™: Effective in Treating VMS
Associated With Menopause
Efficacy demonstrated at 100 mg, 150 mg in
2 placebo-controlled studies
Primary efficacy – number and severity of
VMS
Secondary efficacy – responder analysis,
onset of action, number of awakenings at
night due to VMS
107. Pristiq™: Effective in Reducing
Number of Moderate and Severe VMS
Study 315 Study 319
13 13
12 12
11 11
10 10
# of Flushes
9
# of Flushes
9
8 8
Placebo
Placebo
7 7
6 6
Pristiq
150 mg
5 5 Pristiq 100 mg
Pristiq
4 4
100 mg
Pristiq 150 mg
3 3
2 2
0 1 2 3 4 5 6 7 8 9 10 11 12 01 23 45 678 9 10 11 12
Weeks
Weeks
100 mg dose: p-value versus placebo < 0.05 at all time points
150 mg dose: p-value versus placebo < 0.05 at all time points
108. Pristiq™: Reduction in Average Daily
Number and Severity Score of Hot Flushes
Study 315, 100 mg Study 319, 100 mg
n=145 n=162
Time Point p-Value vs p-Value vs p-Value vs p-Value vs
Placebo Placebo Placebo Placebo
Number Severity Number Severity
Week 1 <0.001 <0.001 <0.001 <0.001
Week 2 <0.001 0.001 <0.001 <0.001
Week 3 <0.001 0.003 <0.001 <0.001
Week 4 0.013 0.054 <0.001 <0.001
Week 5 0.020 0.019 <0.001 0.004
Week 6 0.026 0.048 <0.001 0.002
Week 7 0.019 0.042 <0.001 0.003
Week 8 0.018 0.029 0.001 0.005
Week 9 0.008 0.011 0.001 0.004
Week 10 0.013 0.018 <0.001 0.001
Week 11 0.013 0.004 0.002 0.002
Week 12 0.005 0.002 0.002 0.002
ITT LOCF
109. High Responder Rate in VMS
60%
Study 315 Study 319
% Subjects With > 75 %
Reduction in Hot Flushes
*
*
*
*
40%
20%
0%
Pristiq Pristiq
Placebo
Placebo Pristiq™ Pristiq
100 mg 150 mg
100 mg 150 mg
* p-value versus placebo <0.05
110. Rapid Onset of Action
Time (Days) to Reach a 50% Reduction in Number of VMS
30
Study 315 Study 319
25
Time in Days
20
15
10
* *
*
*
5
0
Pristiq Pristiq
Placebo
Placebo Pristiq™ Pristiq
100 mg 150 mg
100 mg 150 mg
* p-value versus placebo <0.001
111. Reduces Nighttime Awakenings
Due to VMS
Pristiq Pristiq
Placebo
Placebo Pristiq™ Pristiq
100 mg 150 mg
100 mg 150 mg
0.00
Reduction in Number of Nighttime
-1.00
Awakenings
-2.00
* **
* *
Study 315 Study 319
-3.00
* p-value versus placebo <0.05; ** p-value versus placebo <0.001
112. Improves Mood in Non-Depressed
Postmenopausal Women
Week 12 Data
Total Mood Tension
Score Anger Hostility Anxiety Depression Fatigue
0
POMS, Change From Baseline
*
-5 * * *
* *
-10
-15
*
-20 *
Placebo Pristiq™ 100 mg Pristiq 150 mg
-25
* p-value versus placebo <0.05;
Data on File (Pooled data from Studies 315 and 319)
114. Safety and Tolerability Profile of Pristiq™
(Adverse Reactions ≥ 5%)
Consistent With the SNRI Class
Asthenia Nervousness
Hypertension Somnolence
Anorexia Tremor
Constipation Sweating
Dry Mouth Abnormal Vision
Nausea Mydriasis
Vomiting Abnormal Ejaculation/Orgasm
Dizziness Impotence (Male)
Insomnia
Most common adverse drug reactions (>5%), pooled data VMS+MDD
116. MDD Program: Most Nausea
Occurred During Week One
MDD Pooled Fixed Dose Studies
50%
Incidence of Nausea
Placebo (n=323)
40% Pristiq™ 100 mg (n=118)
Pristiq 200 mg (n=307)
Pristiq 400 mg (n=317)
30%
20%
10%
0%
1 2 3 4 6 8 8
Week of Treatment
Wyeth data on file (MDD001 DAR)
117. MDD Program: Incidence of
Discontinuation for Nausea By Week
50
Placebo
40
Pristiq™ 100 mg
% Subjects
30 Pristiq 200 mg
Pristiq 400 mg
20
10
0
Week 1 Week 2 Week 3 Week 4
Subjects in DVS SR Flexible Dose studies (309 and 317 @ 200-400 mg/day) are not included in this display
118. VMS Program: Most Nausea Occurred
During Week One and Was Dose Dependent
VMS Pooled Studies
50%
Placebo (n=323)
Incidence of Nausea
40% Pristiq™ 50mg (n=149)
Pristiq 100mg (n=495)
30%
Pristiq 150mg (n=336)
Pristiq 200mg (n=409)
20%
10%
0%
1 2 3 4 5-8 >12
12
Weeks of Treatment
Wyeth data on file
119. Pristiq™ – Additional Features
No prolongation of QT interval
From thorough QTc study
Blood pressure, pulse rate increases consistent
with SNRIs
100 mg/day: No consistent increase/decrease
Pristiq very low drug-drug interactions
120. Pristiq™ Phase 3 Summary
Efficacy
MDD improved Ham-D17 – 100, 200 and 400 mg
VMS reduced number/severity hot flushes – 100, 150 mg
Sleep, mood, awakenings due to hot flushes reduced
Total mood score improved
Satisfaction score positive – 100, 150 mg
Safety
Early discontinuation rate below 10% at end of week 1
Tolerability profile improved after week 1
Predominant symptoms – nausea, dizziness, insomnia,
somnolence
Median duration of nausea: 3-4 days
121. Pristiq™ Low-Dose Program
MDD
3 ongoing low-dose studies
50, 100 mg, placebo (2 studies U.S., EU)
50, 100 mg, placebo, duloxetine
1 low-dose study to support registration in Asia
Low-dose drug-drug interaction studies underway
VMS
Titration study – 25, 50, 100 mg (ongoing)
122. Conclusion
Pristiq™ provides a unique therapy for women
transitioning through menopause and beyond
MDD
Effective antidepressant in men/women
May provide better efficacy in women
than SSRIs
VMS – non-hormonal vasomotor symptom
relief associated with menopause
Fibromyalgia – clinical program ongoing
124. Pristiq™ Will Broaden
the Reach of Our SNRI Franchise
Major
Major
Depressive
Depressive
Disorder
Disorder
Generalized
Generalized
Anxiety
Anxiety
Disorder
Disorder
Social
Social
Anxiety
Anxiety
Disorder
Green = Effexor XR® Disorder
Panic
Panic
Disorder
Disorder
125. Pristiq™ Will Broaden
the Reach of Our SNRI Franchise
Major
Vasomotor Major
Vasomotor Fibromyalgia
Fibromyalgia
Depressive
Symptoms of Depressive
Symptoms of Syndrome
Syndrome
Disorder
Menopause Disorder
Menopause
Generalized
Generalized
Anxiety
Anxiety
Disorder
Disorder
Social
Social
Anxiety
Anxiety
Disorder
Green = Effexor XR® Disorder
Blue = Pristiq™
Panic
Panic
Disorder
Disorder
Red = Effexor/Pristiq
126. Pristiq™ Product Profile
for Major Depression or VMS
Can become the first and only SNRI proven to
effectively address the distinctive symptoms and
therapeutic needs of women with depression
associated with menopause or vasomotor
symptoms
MDD NDA Dec 2005
Status
VMS NDA June 2006
Peak Sales > $2 Billion
127. Viviant™/Aprela™
(Bazedoxifene)
and
(Bazedoxifene/Conjugated Estrogens)
Alliance with Ligand Pharmaceuticals
128. Initial Target Profile
Viviant™ (Bazedoxifene)
Effective osteoporosis agent
Less potential to exacerbate hot flushes
Safe for breast and uterus
Minimal metabolic disturbances
129. Evolving Target Profile
Viviant™ (Bazedoxifene)
Effective osteoporosis agent
Less potential to exacerbate hot flushes
Safe for breast and uterus
Minimal metabolic disturbances
130. The Number of Women at Risk
for Osteoporosis Is Projected to Increase
From 30 to 41 Million by 2020
45
41 Million
Osteoporosis Osteopenia
40
# of Women in Millions
35
30 Million
30
30
25
Increase
20 22
15
10
11
5 8
0
2002 2020
Source: National Osteoporosis Foundation
131. The Majority of Women Who Stopped
Taking ET/HT Did Not Switch to
Prescription Osteoporosis Brands
18
16.0 Million Osteo Brands
16
Est. Patients in Millions
Oral ET/HT
14 4.4
11.2 Million
12
+ 1.0M
10
5.4
8
6 11.6
- 5.8M
4
5.8
2
0
Pre-WHI Post-WHI
Jan-Jun 2002 Jan-Jun 2004
Source: Patient estimates derived using IMS National Prescription Audit data
132. Viviant™
(Bazedoxifene)
With FDA-approval, the first new SERM
in nearly 10 years providing physicians a
new option for patients at risk of
osteoporosis and fracture
133. New Paradigm
for Menopause
Select Estrogen “Targets”
Patient Benefits
Prevent osteoporosis
Relief of vasomotor
Vasomotor
symptoms
Improved vulvovaginal Breast
atrophy
Neutral on breast Bone
Amenorrhea Endometrium
Endometrial protection Vagina
without progestin
Improved quality of life
136. Aprela™: The Most Comprehensive
Medicine for Menopause
TSEC
Vasomotor
Vasomotor
Breast
Breast
Bone
Bone
Endometrium
Endometrium
Vagina
Vagina
137. Aprela™ and Viviant™
(Bazedoxifene/Conjugated Estrogens)
and
(Bazedoxifene)
Ginger Constantine, M.D.
Vice President and Therapeutic Area Director
Woman’s Health and Bone Repair
Clinical Research & Development,
Wyeth Pharmaceuticals
138. Climacteric Complaints Related to
the Menopause
Occurs in ~50% of Women
Flushing Irritability
Night sweats Lack of self-confidence
Waking at night Insomnia
Tiredness Painful intercourse
Depressed mood Vaginal dryness
139. Menopause Specific Quality-of-Life
(MenQOL)
Vasomotor
Menopausal Stage
Domain Score
Premenopause 1.53
Postmenopause 3.20
p-Value <0.0001
Adapted from Blumel JE, et al. Maturitas 34:17-23, 2000
140. The Majority of Women
Will Suffer Hot Flushes
70%
Hot Flush
60%
50%
% of Women
40%
30%
20%
10%
0%
38 44 46 50 52 54 56 58 60 62 66 72
Age in Years
Source: Rodstrom K et al. Menopause 9(3): 156-161, 2002
141. Osteoporosis
Osteoporotic fracture:
Profound effect on health
↑ Mortality following hip fracture
↑ Disability
↓ Quality-of-Life (QOL)
Huge economic impact
U.S. costs ~ $17.9 billion/year
Increase in hip fractures after
discontinuing HT following WHI†
Abstract: RM Dell, MD et al; Presented: AAOS Annual Mtg March 22-26, 2006
†
143. Architectural Change
One Year Postmenopause
Baseline 1 Year
Borah, et al; Dufresne, et al; Abstracts presented: OI World Congress on Osteoporosis, 2002.
144. Aprela™
(Bazedoxifene/Conjugated Estrogens)
Tissue Selective Estrogen Complex (TSEC)
A New Paradigm for Menopausal Therapy
145. Clinical Rationale for a Tissue Selective
Estrogen Complex (TSEC)
Current HT and SERMs have clinical drawbacks
TSEC may provide improved clinical benefits
with fewer potential side effects
Program initiated in 1999
Maintain Leadership in Menopausal Health
146. Women’s Health Initiative
Estrogen Alone Arm
Cumulative Hazard for Total Breast Cancers
0.04
HR, 0.82
(95% CI, 0.65-1.04)
Log-Rank p =.10
0.03
Cumulative Hazard
0.02
0.01
CEE Alone
Placebo
0.00
0 1 2 3 4 5 6 7 8 9
Time, years
Adapted from Stefanick, M. L. et al. JAMA 2006;295:1647-1657.
147. Optimal Targeted Response of
Tissue Selective Estrogens Complex (TSEC)
Target TSEC
Increased Bone Mass
Improved Hot Flush
Vaginal Health
Prevent Endometrial Hyperplasia
Decreased Breast Tenderness
The Most Comprehensive Medicine
for Menopause
148. Tissue Selective Estrogen Continuum
Defines Activity
Full Full
TSEC
Antagonist Agonist
Aprela™
Estrogen Receptor
Anti-Estrogens Bazedoxifene 17β-Estradiol
Raloxifene
149. Tissue Selective Estrogen Continuum
Defines Activity
Endometrial
Antagonist Agonist
Stimulation
Viviant™ Tamoxifen 17β-Estradiol
Raloxifene Lasofoxifene
Viviant’s Endometrial Profile Permits
TSEC Benefits
M.B. Taylor, North American Menopause Society, October 2004
150. Raloxifene and 17ß-Estradiol
NAMS Abstract
Pilot Study on the Endometrial Effects of Combined
Raloxifene and Oral 17-beta Estradiol in Postmenopausal
Women
M.B. Taylor, MD1, Y. Qu, Ph.D.1, S. Siddhanti, PhD1, L. Plouffe Jr, MD1.
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN.
Results….. By 52 weeks, ET (endometrial thickness) was
significantly increased in the RLX+E group compared with
baseline and the RLX group (p<0.05). Two women (4%) in
RLX+E group and none in the RLX group had endometrial
hyperplasia in the exit endometrial biopsy.
Abstract Presented: NAMS 15th Annual Meeting, Washington, DC; October 2004
151. Aprela™
(Bazedoxifene/CE)
A New Paradigm
Relieve vasomotor symptoms
Prevent osteoporosis
Improve vulvovaginal atrophy (VVA)
Excellent amenorrhea
No increased breast tenderness
vs placebo
Provide endometrial protection
Improve quality-of-life
152. Aprela™ Effectively Treats
Vasomotor Symptoms
Number of Moderate-to-Severe Symptoms
Phase 3 Study
0
Placebo
A djuste d M e a n C ha nge
-2
Fro m B a se line
Raloxifene
-4
-6
Aprela 20/0.625
-8
Aprela 20/0.45
-10
0 1 2 3 4 5 6 7 8 9 10 11 12
Week
Statistically significant at all end points vs placebo and 8 – 12 weeks vs raloxifene
Data on file: Ph 3 BZA/CE analysis 3115A1-303 study
