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Pfizer: Sharing our Vision for Adult Vaccines Kathrin U. Jansen, PhD Senior Vice President & Head of Vaccine Research & Development, Pfizer Immunization of the Elderly (WHO) Geneva, 22-23 March 2017
2
Ageing in the 21st Century
• Reductions of mortality in all ages have added extra years of life to individuals globally
• Increasing life spans likely continue, but gains may be offset unless accompanied by increasing good health
• Ageing individuals and societies demand a comprehensive, systematic methodology to achieve longer/healthier lives
• Such programs must and will include vaccines for the elderly
3
Pfizer’s Vision: Vaccines to Protect Against Infectious Disease and Cancer
Group B Streptococcus
(GBS)
Respiratory Syncytial Virus
(RSV)
Cytomegalo virus (CMV)
Vaccine based immunotherapy
and Oncolytic virus
platforms
to address high unmet need tumor types
Prevnar 13
NextGen Prevnar
Staphylococcus aureus
Clostridium
difficile
Group B Streptococcus
RSV
Nimenrix (Meningococcal
A, C, Y, W conjugate)
Trumenba
(Meningococcal B)
Prevnar 13 (Pneumococcal
conjugate)
Broadly protective influenza
4
CAPiTA Trial Design and Timeline
R: Randomization; VT: Vaccine-Type; CAP: Community-Acquired Pneumonia. Hak E, Grobbee DE, Sanders EAM, et al. Netherlands J Med. 2008;66:378-383 CAPiTA: Community Acquired Pneumonia immunization Trial in Adults Bonten M et al, (2015) NEJM 372, 1114-25
Sept 2008 Jan 2010 Sept 2011 Aug 2013 2014 20
Regulatory Review of Primary and
Secondary Outcome Data
Interim Analysis
Reached Required Number of Confirmed
VT-CAP Cases
Accrual of VT-CAP Cases
R
Placebo
PCV13
Screening and Recruitment
84,496 Volunteers
≥ 65 years of age
US/EU filings
2015
SSUAD
US/EU approvals/re-
commendations
5
CAPiTA Outcome Primary and Secondary Objectives: Per Protocol Population
*95% Confidence Interval. Bonten et al 2015 NEJM 372:12 CAPiTA: Community Acquired Pneumonia Immunization trial in Adults
Efficacy Endpoint
Vaccine Group
VE (%) 95.2% CI p-Value PCV13
(n=42,240) Placebo
(n=42,256) First Episode of Confirmed VT Pneumococcal CAP 49 90 45.6 (21.8,62.5) <0.001
First Episode of Confirmed NB/NI VT Pneumococcal CAP 33 60 45.0 (14.2, 65.3) 0.007
First Episode of VT-IPD 7 28 75.0 (41.4, 90.8)* <0.001
Vaccine-Type CAP NB and NI CAP Vaccine-Type IPD
Post Hoc Analysis of the Cumulative Episodes of the Primary and Secondary Efficacy End Points in the Per Protocol Population
6
Incidence of US CAP (Hospitalized Adults 65 Years and Older)
(P) Represents a prospective cohort/surveillance study. Ramirez J, Wiemken T, et al. Risk for Hospitalization Due to Community-Acquired Pneumonia (CAP) in Non-Elderly Patients with Comorbid Conditions: The Louisville Pneumonia Study. Poster 044. ISPPD-10. Glasgow, UK. Jun 2016.
Time
1,014 1,150
1,230
1,796
1,997
1,643
1,375
897
2,327
0
500
1,000
1,500
2,000
2,500
Marston et al.1991(P)
Jackson et al.1998-2001
Nelson et al.1998-2004
Yu et al.2007-2008
Griffin et al.2007-2009
Shea et al.2006-2010
Simonsen et al.2011-2012
Jain et al.2010-2012
(P)
Ramirez et al.2014-2015
(P)
(P) Represents a prospective cohort/surveillance study. 20
14 C
DC
65+
1.7x
Annual Incidence of Hospitalized CAP per 100,000 in Adults 65+
7
Invasive Pneumococcal Disease in US Adults ≥65 Years of Age
*PPSV23 serotypes: 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, AND 33F *PCV13 serotype: 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, AND 23F Active Bacterial Core surveillance data, 1998-2015, unpublished
Trends in Invasive Pneumococcal Disease Among Adults Aged >65 Years Old, 1998-2015
59 60 58
51
43 42 38 36
40 39 41 39 36 35
29 31
25 26
51 50 49
42
34 32 27 26 27 26 27 26
23 22 18 18
13 15
44 46 43
36
29
23 20 18 17 17 18 17
14 11 9 7 5 6
0
10
20
30
40
50
60
70
1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015
Cas
es P
er 1
00,0
00
Year
All IPD PPSV23 Type PCV13 Type
PCV7 Introduction
PCV7 Introduction for Children
PCV13 Recommendations for Immunocompromised Adults 19+
PCV13 Recommendations for Adults 65+
8
S. aureus Disease Has Diverse Manifestations and Affects Many Patient Populations (US Data Only)
SA=S. aureus; MRSA=methicillin-resistant Staphylococcus aureus; MSSA=methicillin-sensitive Staphylococcus aureus. 1. Foster T. Staphylococcus. In: Baron S, ed. Medical Microbiology. Galveston, TX: University of Texas Medical Branch at Galveston; 1996. 2. Liu C et al. Clin Infect Dis 2011;52:285-292. 3. Cunha BA. Clin Microbiol Infect 2005;11(suppl 4):33-42. 4. Yu H et al. ICAAC 2012. September 9-12, 2012. San Francisco, CA. Presentation K259. 5. Styers D et al. Ann Clin Micro Antimicrob 2006;5:2. 6. Kuehnert MJ et al. J Infect Dis 2006;193:172-179. 7. von Eiff C et al. N Engl J Med. 2001;344:11-16. 8. Hersh AL et al. Arch Intern Med. 2008;168:1585–1591. 9. Centers for Disease Control and Prevention. MRSA and the workplace [updated 19 September 2014]. Available from: http://www.cdc.gov/niosh/topics/mrsa/. 10. Laupland KB et al. J Infect Dis. 2003;187:1452-1459. 11. Dancer SJ. Lancet Infect Dis. 2008;8(2):101-113. 12. National Nosocomial Infections Surveillance System. Am J Infect Control 1996;24(5):380-388.13. Eili Klein*, David L. Smith†, and Ramanan Laxminarayan. Hospitalizations and Deaths Caused by Methicillin-Resistant Staphylococcus aureus, United States, 1999–2005. Volume 13, Number 12—December 2007 Research. 14 Koeck et al, Invasive Staphylococcus aureus Infections in Minnesota: A Large Role for MSSA. IDWeek 2015. 15. CDC. 2014. Active Bacterial Core Surveillance Report, Emerging Infections Program Network, Methicillin-Resistant Staphylococcus aureus, 2014. Available via the Internet: http://www.cdc.gov/abcs/reports-findings/survreports/mrsa14.htmll.16. CDC data (Scott Fridkin/CDC) (June 7, 2016) 17 http://www.cdc.gov/nchs/fastats/inpatient-surgery.htm (removed diagnostic procedures and percutaneous procedures as possible, e.g., endoscopy and cardiac catheritization)
Disease severity
Size of affected population
• 190,000 invasive SA infections in the US annually14, 15
• 260,000 SA wound infections annually16
• 180 SA SSI per 100,000 NHSN surgical procedures16
• 20,000 deaths due to S. aureus in the US annually13
• 32 M surgeries in the US annually17
Skin and Soft Tissue Infection (SSTI) Carbuncle, impetigo, cellulitis, wound/burn
infection, abscess, SSI1,2,12
Carriage/Colonization Anterior nares, oropharynx, GI, skin, vagina10
Metastatic Infection
Endocarditis, osteomyelitis,
device- related1,2
Deep Infection Surgical site infection (SSI)
Arthritis, mediastinitis, osteomyelitis, Device-related pneumonia1,2,12
Bloodstream Infection (BSI)
• Hemodialysis patients9
• Nursing home residents8
• 9.6 million abscess or cellulitis cases diagnosed in ambulatory settings in US (2005)7
• ~30% adults colonized5
• ~82% bacteremia due to colonizing strain6
9
S. Aureus: Design of SA4Ag Vaccine Trial (Phase 2)
Frenck, R., et al 2014. Open Forum Infectious Diseases. 1(S1) 600. Proceedings from ID Week (Joint meeting of IDSA, SHEA, HIVMA and PIDS), Philadelphia, PA, Oct 8-12, 2014
• Subjects had a mean age of 45.0 years, 56.8% were female, and 73.2% were white
• 87.5% of subjects completed the study through Month 12 R
ando
miz
atio
n
456 Participants Enrolled at 13 US Sites
18 to 49 Years (n=233)
50 to 64 Years (n=223)
Low-dose rP305A (n=117)
Mid-dose rP305A (n=114)
High-dose rP305A (n=113)
Placebo (n=112)
10
Safety Summary
AE, adverse event Frenck, R., et al 2014. Open Forum Infectious Diseases. 1(S1) 600. Proceedings from ID Week (Joint meeting of IDSA, SHEA, HIVMA and PIDS), Philadelphia, PA, Oct 8-12, 2014
Local Reactions Reported Through Day 14
• Local reactions generally were mild or moderate in severity
• Systemic events and other AEs were comparable across SA4Ag and placebo groups
• No vaccine-related serious AEs or deaths were reported
0
10
20
30
40
Injection SitePain
Swelling Redness
Perc
enta
ge o
f Sub
ject
s R
epor
ting
Placebo (n=112)Low-dose rP305A (n=116)Mid-dose rP305A (n=114)High-dose rP305A (n=112)
11
SA4Ag Elicited Immune Responses Rise Rapidly and Are Sustained Through Month 12
Frenck, R., et al 2014. Open Forum Infectious Diseases. 1(S1) 600. Proceedings from ID Week (Joint meeting of IDSA, SHEA, HIVMA and PIDS), Philadelphia, PA, Oct 8-12, 2014
Low-dose Mid-dose High-dose Placebo
CP8 (OPA) CP5 (OPA)
P305A (cLIA) CIfA (cLIA)
12
SA4Ag Immune Responses Are Not Dramatically Affected by Age
Frenck, R., et al 2014. Open Forum Infectious Diseases. 1(S1) 600. Proceedings from ID Week (Joint meeting of IDSA, SHEA, HIVMA and PIDS), Philadelphia, PA, Oct 8-12, 2014
CP5 (OPA)
13
Clostridium Difficile: A Significant Unmet Medical Need in Older Adults
Bacteria express toxins causing severe diarrhea
C. difficile at “Hazard Level – Urgent” (CDC)
>450,000 cases and >29,000 deaths/year
in US
Antibiotic use causes C. difficile infection
Currently There is No Vaccine to Prevent Initial or Recurrent Infections
1. Lucado J, et al. Healthcare Cost and Utilization Project (HCUP) Statistical Briefs [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2006–2012 Jan. 2. Giannasca PJ, et al. Infect Immun. 1999;67(2):527-538. 3. Torres JF, et al. Infect Immun. 1995;63(12):4619-4627. 4. Lessa FC, et al. N Engl J Med. 2015;372:825.
14
Robust C. Difficile Toxin Neutralizing Immune Response Observed with Genetically Detoxified Toxoids (Phase 1, Evaluable Immunogenicity Population)
Sheldon et al Vaccine 2016:34:2082-91
Toxin B-Specific Neutralizing Antibody GMC (65- to 85-Year Age Cohort)
15
Complex Barriers to Adult Vaccination • Some vaccines are universally recommended for adults, while others
are recommended for certain age groups, targeted to individuals with specific risk factors or targeted to particular combinations of age and risk factors
Low level of patient awareness
Lack of available public health information
Lack of adult disease and vaccine surveillance
Lack of medical/scientific recommendation
Low level of government support for adult prevention and vaccines
Lack of reimbursement or willingness to vaccinate adults
Lack of adult vaccine administration settings/schedules
Low level of healthcare provider awareness of vaccine benefits
Recommended