1

ACIP February 22, 2023

20-valent Pneumococcal 

Conjugate Vaccine

(PCV20) Phase 3 

in Pediatrics

Wendy Watson, MD

Global Clinical Program Lead
2

PCV20 is Built on the Established Platforms of PCV7 and PCV13

CRM197

Real-World Effectiveness

Real-World Impact

Clinical Efficacy

PCV7

Immunogenicity & Safety 

PCV13

PCV20

PCV7

Real-World Effectiveness

Real-World Impact

PCV13

Immunogenicity & Safety

Efficacy from immunobridging

Data available after vaccine implementation

PCV20

Immunogenicity & Safety

Efficacy from Immunobridging

Real-World Effectiveness

Real-World Impact

4 6B 9V 14 18C 19F 23F 1 3 5 6A 7F 19A 8 10A 11A 12F 15B 22F 33F

PCV20 

Composition

• PCV20 builds on the 20-year legacy of PCVs and contains PCV13 components + conjugates for 7 additional 

serotypes to broaden disease coverage for pneumococcal disease in children

• The 7 additional conjugates were modelled on the PCV13 Pfizer platform

• Licensure based on satisfactory safety and immunogenicity compared to PCV13

• Totality of data to support comparability per regulatory agreement

• Seeking same indications as PCV13

• PCV20 in the pediatric program is the same vaccine currently approved, recommended, and administered in 

adults

Licensure and 

Indications
3

PCV20 Clinical Development Program

Senders 

et al. 2021

2, 4, 6 and 

12 months 

of age

460

Participants

Demonstrate safety, tolerability, and immunogenicity of PCV20

• Concomitant administration with Pediarix

• United States

Pivotal Infant 

Study

2, 4, 6 and 

12–15 months 

of age

1997

Participants 

Demonstrate noninferiority of immune response of PCV20 vs PCV13 

• Concomitant administration with Pediarix, Hiberix, M-M-R II, Varivax

• United States, Puerto Rico

Pediatric 

Single Dose 

Study

Single dose 

(15 months–

<18 years 

of age)

831

Participants

Characterize safety and immunogenicity in children 15 months to 

17 years of age

• United States

Safety 

Study

2, 4, 6 and 

12–15 months

of age

1511

Participants

Further characterize safety profile of PCV20

• Concomitant standard vaccines allowed

• United States, Puerto Rico, Canada, Chile, Argentina, European Union

SAFETY

IMMUNOGENICITY

Phase 2 Phase 3
4

Study Design of Phase 3 Pivotal Study in Infants

Blood draws Safety follow-up call

Control Group

PCV20 Group

+

Pediarix, 

Hib

Age 6 

months 

2 

months

4 

months

7 

months 

12-15 

months

13-16 

months

18-21 

months

+

Pediarix, 

Hib

+

Pediarix, 

Hib

+

Pediarix, 

Hib

+

Pediarix, 

Hib

+

Pediarix, 

Hib

+

MMR and 

Varicella

+

MMR and 

Varicella

PCV20 PCV20 PCV20 PCV20

PCV13 PCV13 PCV13 PCV13

PCV20

N*=1001

PCV13

N*=987

Sex n†(%) n†(%)

Male 518 (51.7) 505 (51.2)

Race

White 754 (75.3) 742 (75.2)

Black or African 

American 110 (11.0) 108 (10.9)

Asian 16 (1.6) 16 (1.6)

American Indian or 

Alaska Native 4 (0.4) 3 (0.3)

Native Hawaiian or 

other Pacific 

Islander

2 (0.2) 2 (0.2)

Multiracial 68 (6.8) 73 (7.4)

Ethnicity

Hispanic/Latino 312 (31.2) 293 (29.7)

Non-Hispanic/

non-Latino 661 (66.0) 659 (66.8)

Multicenter, Randomized, Double-blind Study in the 

US/Puerto Rico Study in Infants (92 sites, n=1997)

Similar Demographics of PCV20 

and PCV13 Groups

• Concomitant Influenza and rotavirus vaccines permitted at 

any time during trial

Pivotal Infant Study

*N=number of participants in the specified age cohort. This value is the denominator for the percentage calculations.

†n=number of participants with the specified characteristic.

PCV20

N*=1001

PCV13

N*=987

Sex n†(%) n†(%)

Male 518 (51.7) 505 (51.2)

Race

White 754 (75.3) 742 (75.2)

Black or African 

American 110 (11.0) 108 (10.9)

Asian 16 (1.6) 16 (1.6)

American Indian or 

Alaska Native 4 (0.4) 3 (0.3)

Native Hawaiian or 

other Pacific 

Islander

2 (0.2) 2 (0.2)

Multiracial 68 (6.8) 73 (7.4)

Ethnicity

Hispanic/Latino 312 (31.2) 293 (29.7)

Non-Hispanic/

non-Latino 661 (66.0) 659 (66.8)
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Primary 

Objectives

Co-primary: Noninferiority of IgG GMCs after 

toddler dose

Co-primary Noninferiority of % of participants with 

IgG above predefined levels after infant series

NI for GMC ratio (GMR) = the lower bound of 2-sided 95% CI for GMR (PCV20/PCV13) >0.5.

NI for difference in percentages of participants = the lower bound of 2-sided 95% CI for percent difference (PCV20-PCV13) > -10%.

Pre-specified Immunogenicity Analyses

• OPA GMTs after infant series and 

toddler dose 

• % with OPA titers ≥ LLOQ after infant 

series and toddler dose 

• OPA titer RCDC after infant series and

toddler dose

Circulating IgG Antibody Functional Response Memory Response

• % above prespecified IgG level after 

toddler dose

• IgG GMCs and % above prespecified 

IgG for the 7 additional serotypes 

relative to the PCV13 group

• IgG Reverse Cumulative Distribution 

Curve (RCDC) after infant series and 

toddler dose

Additional Data

• Concomitant Vaccine Antigen GMCs 

and GMRs

• Comparison of % With Prespecified 

Antibody Levels for Concomitant 

Vaccine Antigens

• Explore cross protection to 6C and 15C

• Geometric fold-rises (GMFR) of IgG 

from after infant series to after the 

toddler dose 

• GMFR of IgG from before to after the 

toddler dose

• GMFR of OPA from after infant series to 

after the toddler dose 

• % with ≤ 4-fold rise in OPA titers from 

before to after the toddler dose 

Key 

Secondary 

Objective

Noninferiority of IgG GMC after infant series

Importance of Multiple Immunologic Assessments to Infer Effectiveness 

Pivotal Infant Study
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Post Dose 3: Percentage with Predefined IgG Concentrations

Serotype

PCV13

PCV20

(%)

PCV13

(%)

Difference (%)

(95% CI)

1 79.8 88.4 -8.6 (-12.1, -5.1)

3 52.1 67.6 -15.5 (-20.1, -10.8)

4 79.7 88.2 -8.4 (-12.0, -4.9)

5 82.5 86.8 -4.3 (-7.8, -0.8)

6A 93.5 95.9 -2.4 (-4.6, -0.2)

6B 88.3 92.4 -4.1 (-7.0, -1.2)

7F 96.6 97.6 -1.0 (-2.7, 0.7)

9V 81.9 89.8 -7.9 (-11.3, -4.6)

14 93.4 94.1 -0.8 (-3.1, 1.6)

18C 92.6 93.1 -0.6 (-3.1, 1.9)

19A 97.1 98.1 -1.0 (-2.6, 0.5)

19F 96.9 96.6 0.2 (-1.5, 2.0)

23F 77.9 85.5* -7.6 (-11.4, -3.9)

7 Additional

8 96.8 85.5 11.2 (8.6, 14.0)

10A 82.2 85.5 -3.3 (-6.9, 0.3)

11A 92.7 85.5 7.1 (4.2, 10.2)

12F 67.5 85.5 -18.1 (-22.1, -14.0)

15B 98.2 85.5 12.7 (10.2, 15.4)

22F 98.3 85.5 12.8 (10.3, 15.5)

33F 86.7 85.5 1.1 (-2.2, 4.5)

-30 -20 -10 0 10 20 30

Difference in Percentage (PCV20–PCV13)

Co-Primary Objective Pivotal Infant Study

14 Serotypes Met Noninferiority (Difference in %)

*The 7 additional serotypes are compared to the percentage for serotype 23F after Dose 3 (lowest in PCV13 group, excluding serotype 3).

Predefined IgG concentration – ≥0.35 μg/mL for all serotypes except ≥ 0.23 μg/mL, ≥0.10 μg/mL and ≥ 0.12 μg/mL for serotypes 5, 6B and 19A respectively. 
7

Post Dose 3: IgG Concentration and Geometric Mean Ratio 

Serotype

PCV13

PCV20

GMC

PCV13

GMC

GMR

(95% CI)

1 0.74 1.14 0.65 (0.59, 0.72)

3 0.36 0.51 0.70 (0.64, 0.76)

4 0.75 1.08 0.70 (0.63, 0.78)

5 0.66 0.96 0.69 (0.61, 0.77)

6A 1.95 2.69 0.72 (0.65, 0.81)

6B 0.61 1.02 0.60 (0.51, 0.70)

7F 1.71 2.29 0.75 (0.69, 0.81)

9V 0.87 1.21 0.72 (0.65, 0.80)

14 2.16 2.72 0.79 (0.71, 0.89)

18C 1.31 1.71 0.77 (0.70, 0.84)

19A 0.72 0.91* 0.79 (0.72, 0.86)

19F 1.59 2.00 0.79 (0.73, 0.86)

23F 0.82 1.25 0.66 (0.58, 0.75)

7 Additional

8 1.80 0.91 1.98 (1.81, 2.16)

10A 1.21 0.91 1.32 (1.18, 1.49)

11A 1.39 0.91 1.52 (1.39, 1.67)

12F 0.55 0.91 0.60 (0.54, 0.67)

15B 4.40 0.91 4.82 (4.39, 5.30)

22F 3.71 0.91 4.06 (3.68, 4.48)

33F 1.49 0.91 1.64 (1.46, 1.83)

0.25 0.5 1 2 4 8

GMR

Key Secondary Objective Pivotal Infant Study

All 20 Vaccine Serotypes Met Noninferiority

* The 7 additional serotypes are compared to the GMC after Dose 3 for serotype 19A (lowest in PCV13 group, excluding serotype 3).
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Serotype

7 Additional 

PCV20

GMC

PCV13

GMC

GMR

(95% CI)

8 1.80 0.02 100.54 (91.58, 110.38)

10A 1.21 0.01 99.64 (88.87, 111.70)

11A 1.39 0.02 91.03 (82.79, 100.09)

12F 0.55 0.01 68.42 (62.47, 74.94)

15B 4.40 0.03 169.40 (154.01, 186.33)

22F 3.71 0.01 730.84 (651.36, 820.01)

33F 1.49 0.02 97.45 (86.96, 109.21)

Post Dose 3: IgG Concentration and Geometric Mean Ratio 

Pivotal Infant Study

Statistically Significantly Higher Response when compared to actual PCV13 Response

0.25 0.5 1 2 4 8 16 32 64 128 256 512 1024

GMR

Comparison of additional 7 serotypes to actual PCV13 IgG GMC, not lowest in PCV20 group
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PCV20 (n= 80–105); PCV13 (n=77–113).

Post Dose 3: Comparison of PCV20 and PCV13 OPA GMTs

Pivotal Infant Study

Functional Antibody Responses Were Similar Between PCV20 and PCV13 for

Shared Serotypes 

Post Dose 3

1

10

100

1000

10000

1 3 4 5 6A 6B 7F 9V 14 18C 19A 19F 23F 8 10A 11A 12F 15B 22F 33F

OPA GMTs

PCV20 PCV13
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Post Dose 4: IgG Concentration and Geometric Mean Ratio

Serotype

PCV13

PCV20

GMC

PCV13

GMC

GMR Ratio

(95% CI)

1 1.47 2.12* 0.69 (0.63, 0.76)

3 0.56 0.85 0.66 (0.61, 0.73)

4 3.77 4.84 0.78 (0.70, 0.86)

5 1.87 2.51 0.74 (0.67, 0.82)

6A 9.01 11.69 0.77 (0.70, 0.85)

6B 4.01 5.74 0.70 (0.62, 0.79)

7F 3.91 5.18 0.76 (0.70, 0.82)

9V 3.44 4.30 0.80 (0.73, 0.88)

14 5.68 6.34 0.90 (0.81, 1.00)

18C 3.46 4.69 0.74 (0.67, 0.82)

19A 3.53 4.13 0.85 (0.77, 0.94)

19F 5.01 5.79 0.86 (0.78, 0.96)

23F 3.95 6.18 0.64 (0.57, 0.72)

7 Additional

8 3.97 2.12 1.87 (1.71, 2.06)

10A 6.22 2.12 2.94 (2.64, 3.26)

11A 3.53 2.12 1.67 (1.51, 1.84)

12F 1.85 2.12 0.88 (0.79, 0.97)

15B 12.59 2.12 5.95 (5.39, 6.55)

22F 10.60 2.12 5.01 (4.54, 5.52)

33F 9.31 2.12 4.40 (3.99, 4.85)

0.25 0.5 1 2 4 8

GMR

Co-Primary Objective Pivotal Infant Study

All 20 Vaccine Serotypes Met Noninferiority 

* The 7 additional serotypes were compared to serotype 1 in the PCV13 group (lowest IgG GMC after Dose 4, excluding serotype 3).
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PD3 Compared to PD4: IgG and OPA Response to PCV20

Pivotal Infant Study

Post Dose 3 and Post Dose 4 IgG GMCs 

Post Dose 3 and Pose Dose 4 OPA GMTs

0.01

0.1

1

10

100

1 3 4 5 6A 6B 7F 9V 14 18C 19A 19F 23F 8 10A 11A 12F 15B 22F 33F

IgG GMCs

PCV20 PD3 PCV20 PD4

1

10

100

1000

10000

100000

1 3 4 5 6A 6B 7F 9V 14 18C 19A 19F 23F 8 10A 11A 12F 15B 22F 33F

OPA GMTs

PCV20 PD3 PCV20 PD4

Boosting Observed Across All 20 Serotypes Indicating Anamnestic Response/Memory
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Concomitant Use: Responses to the Vaccines Were Similar When Given 

with PCV20 or PCV13 in the Infant Immunization Series

Post Dose 3: Pediarix and Hiberix® Post Dose 4: MMR ®II and Varivax®

Concomitant 

Vaccine Antigen

PCV20

(%)

PCV13

(%)

Difference (%)

(95% CI)

Diphtheria 93.5 97.8 -4.3 (-7.5, -1.4)

Tetanus 99.7 99.4 0.3 (-1.0, 1.7)

Pertussis

PT 94.9 95.0 -0.2 (-3.5, 3.1)

FHA 95.7 95.0 0.6 (-2.5, 3.9)

PRN 93.8 95.0 -1.3 (-4.7, 2.2)

HBsAg 100.0 100.0 0.0 (-3.2, 2.9)

Poliovirus

Type 1 100.0 100.0 0.0 (-3.4, 3.2)

Type 2 100.0 99.2 0.8 (-2.4, 4.6)

Type 3 100.0 100.0 0.0 (-3.2, 3.1)

Hib 100.0 100.0 0.0 (-3.0, 3.0)

Antigen

(Units)

PCV20

GM

PCV13

GM

GMR

(95% CI)

Measles

(AU/mL) 277.74 215.41 1.29 (1.05, 1.58)

Mumps

(AU/mL) 36.96 34.19 1.08 (0.85, 1.38)

Rubella

(IU/mL) 49.63 40.44 1.23 (1.02, 1.48)

Varicella 

(mIU/mL) 233.05 234.78 0.99 (0.84, 1.17)

0.25 0.50 1.00 2.00

GMR (PCV20:PCV13)

Pivotal Infant Study

All Responses Met Noninferiority

HBsAg = hepatitis B surface antigen; PT = pertussis toxoid, FHA =filamentous hemagglutinin (of Bordetella pertussis), PRN = pertactin (of Bordetella pertussis)

-15.0 -5.0 0.0 5.0 15.0

% Difference (PCV20–PCV13)
13

Systemic Reactions 

Local Reactions 

10.3 7.5

17.3 16.3

12.6 13.7 14.5 14.0

24.4 23.9 26.4 23.5 20.6 22.4 24.8 25.2

67.2 66.0

54.7 55.6

44.1 44.1

39.5 39.5

70.9 71.7 71.6 68.8

64.4 63.0 61.1 61.0

0

20

40

60

80

100

25.5 24.6 23.2 26.4 25.4 27.2 23.5 26.6

16.4 18.8 15.5 17.3 17.1 17.6 14.9 17.3

49.1 45.3 44.1 41.7 38.6 39.0 35.7 35.8

0

20

40

60

80

100

Solicited Reactions within 7 Days of Vaccination

Dose 1 Dose 2 Dose 3 Dose 4 Dose 1 Dose 2 Dose 3 Dose 4 Dose 1 Dose 2 Dose 3 Dose 4

Redness Swelling Injection Site Pain

Fever Decreased Appetite Drowsiness Irritability

Dose 1 Dose 2 Dose 3 Dose 4 Dose 1 Dose 2 Dose 3 Dose 4 Dose 1 Dose 2 Dose 3 Dose 4 Dose 1 Dose 2 Dose 3 Dose 4

Pivotal Infant Study

Reactions Were Similar in Rate and Severity Across All 4 Doses

PCV20: Dose 1=993, Dose 2=940, Dose 3=914, Dose 4=826. PCV13: Dose 1=974, Dose 2=924, Dose 3=901, Dose 4 =814.

Severe 

Moderate 

Mild

PCV20 PCV13

>40.0°C

Severe >38.9–40.0°C

Moderate >38.4–38.9°C

Mild ≥38.0–38.4°C

PCV20 PCV13

%

%
14

15–23 mos

N†=209

2–4 yrs

N†=216

5–9 yrs

N†=201

10–17 yrs

N†=216

Sex n‡(%) n‡(%) n‡(%) n‡(%)

Male 117 (56.0) 106 (49.1) 108 (53.7) 115 (56.1)

Race

White 168 (80.4) 173 (80.1) 174 (86.6) 178 (86.8)

Black or African 

American 26 (12.4) 26 (12.0) 22 (10.9) 17 (8.3)

Asian 3 (1.4) 0 0 0

American Indian or 

Alaska Native 0 1 (0.5) 0 0

Native Hawaiian or 

other Pacific Islander 0 0 0 1 (0.5)

Multiracial 10 (4.8) 13 (6.0) 5 (2.5) 9 (4.4)

Ethnicity

Hispanic/Latino 35 (16.7) 45 (20.8) 31 (15.4) 43 (21.0)

Non-Hispanic/Latino 172 (82.3) 171 (79.2) 168 (83.6) 161 (78.5)

Pediatric Single Dose Study Design and Demographics

Blood draws Safety follow-up call

PCV20 Group

Age

Group

Prior

Vaccination Status Day 1 1 month 6 months

Phase 3 Study Demographic Characteristics –

Safety Population

≥3 doses of PCV13 PCV20 2–4

years*

≥3 doses of PCV13 PCV20 15–23

months*

Not required PCV20 5–9

years

Not required PCV20 10–17

years

Single Dose Study

*Participants <5 years of age had confirmed receipt of >3 prior doses of PCV13.

† N=number of participants in the specified age cohort. This value is the denominator for the percentage calculations. ‡ n=number of participants with the specified characteristic.

15–23 mos

N†=209

2–4 yrs

N†=216

5–9 yrs

N†=201

10–17 yrs

N†=216

Sex n‡(%) n‡(%) n‡(%) n‡(%)

Male 117 (56.0) 106 (49.1) 108 (53.7) 115 (56.1)

Race

White 168 (80.4) 173 (80.1) 174 (86.6) 178 (86.8)

Black or African 

American 26 (12.4) 26 (12.0) 22 (10.9) 17 (8.3)

Asian 3 (1.4) 0 0 0

American Indian or 

Alaska Native 0 1 (0.5) 0 0

Native Hawaiian or 

other Pacific Islander 0 0 0 1 (0.5)

Multiracial 10 (4.8) 13 (6.0) 5 (2.5) 9 (4.4)

Ethnicity

Hispanic/Latino 35 (16.7) 45 (20.8) 31 (15.4) 43 (21.0)

Non-Hispanic/Latino 172 (82.3) 171 (79.2) 168 (83.6) 161 (78.5)
15

IgG GMC in Children Previously Vaccinated with PCV13 

One Dose of PCV20 Elicited Responses to All Vaccine Serotypes

15 to <24 Months

2 to <5 Years

Single Dose Study

0.01

0.1

1

10

100

1 3 4 5 6A 6B 7F 9V 14 18C 19A 19F 23F 8 10A 11A 12F 15B 22F 33F

IgG GMCs

Before PCV20 1 Month After PCV20

0.01

0.1

1

10

100

1 3 4 5 6A 6B 7F 9V 14 18C 19A 19F 23F 8 10A 11A 12F 15B 22F 33F

IgG GMCs

Before PCV20 1 Month After PCV20
16

*SAEs reported are in all sites, not just US (including Puerto Rico). 

B7471003, B7471011, and B7471013 (all sites): (PCV20 N=2232; PCV13 N=1717)

Overall Summary of Adverse Events in the US

Age < 15 months 15 m - <18 yr

PCV20

(N=1567)

PCV13

(N=1376)

PCV20

(N=831)

AEs 43.8% 46.3% 10.7%

Immediate AEs 0.1–0.2% /dose 0.1% /dose 0%

Related AE 1.1% 1.1% 0.1%

Severe AEs 1.4% 1.1% 0.2%

Serious AEs* 4.5%* 3.7%* 0.6%

Related SAEs 0 0 0

Deaths 0 0 0

PCV20 had no Related Serious Adverse Events or Deaths

Overall Safety
17

Summary of PCV20 Pediatric 

PCV20 has the potential to address a substantial burden of pneumococcal disease in children 

PCV20 is well tolerated with a safety profile similar to PCV13 

The totality of data shows PCV20 elicits immune responses to all 20 vaccine serotypes

A single dose of PCV20 elicited a robust immune response to all 20 serotypes and was well tolerated in

children 15 months to < 18 years of age, including those with prior PCV13 

PCV20 is currently under review by the FDA for use in pediatric population 6 weeks to <18 years of age 

with a target action date in April 2023

PCV20 is compatible with routine pediatric vaccines
18

Questions?