Breakthroughs that change patients’ lives Confidential 1

Alejandra Gurtman, MD, FIDSA

Presentation to ACIP

June 21, 2023

RSVpreF Older Adults

Clinical Development Program

Updates
WRDM Worldwide Medical & Safety Confidential 2

ABRYSVOTM (Respiratory Syncytial Virus Vaccine)

FDA Approval on 5/31/2023

RSVpreF Older Adult 

– Clinical Development Program Updates

Indication

Active immunization for the prevention of lower respiratory tract disease (LRTD) 

caused by respiratory syncytial virus (RSV) in individuals 60 years of age and 

older

Additional Clinical Trial Data

• RENOIR – End-of-Season 1 and Mid-Season 2 analyses

• RSVpreF/influenza vaccine coadministration study
WRDM Worldwide Medical & Safety Confidential 3

RENOIR 

– Phase 3 safety and efficacy study in adults ≥ 60 years of age

38,863 participants enrolled

Healthy or with stable chronic conditions

Randomized 1:1 to receive

RSVpreF 120 μg or placebo

Stratified by age group

60−69 years | 70−79 years | ≥ 80 years 
WRDM Worldwide Medical & Safety Confidential 4

Day 1 Day 7 Month 1 Month 6 End Season 1 Start Season 2 End Season 2

RENOIR Study Design 

Reactogenicity 

Subset

(n = 7,169)

Local Reactions

Systemic Events

Immunogenicity 

Subset

(n = 1,050)

All Participants

(N = 36,127) Safety: SAEs, NDCMCs

Safety: Unsolicited AEs

Weekly active surveillance 

for acute respiratory symptoms 

Weekly active surveillance 

for acute respiratory symptoms e e

AE, adverse event; NDCMC, newly diagnosed chronic medical condition; SAE, serious adverse event
WRDM Worldwide Medical & Safety Confidential 5

Day 1 Day 7 Month 1 Month 6 End Season 1 Start Season 2 End Season 2

AE, adverse event; NDCMC, newly diagnosed chronic medical condition; SAE, serious adverse event

RENOIR Study Design 

Reactogenicity 

Subset

(n = 7,169)

Local Reactions

Systemic Events

Immunogenicity 

Subset

(n = 1,050)

All Participants

(N = 36,127) Safety: SAEs, NDCMCs

Safety: Unsolicited AEs

Weekly active surveillance 

for acute respiratory symptoms 

Weekly active surveillance 

for acute respiratory symptoms e e

Season 1 Mid-Season 2
WRDM Worldwide Medical & Safety Confidential 6

Day 1 Day 7 Month 1 Month 6 End Season 1 Start Season 2 End Season 2

AE, adverse event; NDCMC, newly diagnosed chronic medical condition; SAE, serious adverse event

RENOIR Study Design 

Reactogenicity 

Subset

(n = 7,169)

Local Reactions

Systemic Events

Immunogenicity 

Subset

(n = 1,050)

All Participants

(N = 36,127) Safety: SAEs, NDCMCs

Safety: Unsolicited AEs

Weekly active surveillance 

for acute respiratory symptoms 

Weekly active surveillance 

for acute respiratory symptoms e e

Season 1 Mid-Season 2

Average Time 

since Vaccination

Northern and Southern Hemispheres Northern Hemisphere

13.9 months
WRDM Worldwide Medical & Safety Confidential 7

Efficacy against RSV-LRTD 

– Demonstrated through Mid-Season 2 Analysis

Number of Events

RSVpreF Placebo

Season 1 (N = 36,127) 15 43

Mid-Season 2 (n = 20,019) 23 45

65.1%

48.9%

0 20 40 60 80 100

Vaccine Efficacy (%, 95% CI)

RSV-LRTD with ≥ 2 symptoms

Mid-Season 2 includes Northern Hemisphere only (US, Canada, Finland) through January 31, 2023

Number of Events

RSVpreF Placebo

Season 1 (N = 36,127) 2 18

Mid-Season 2 (n = 20,019) 3 14

88.9%

78.6%

0 20 40 60 80 100

Vaccine Efficacy (%, 95% CI)

RSV-LRTD with ≥ 3 symptoms
WRDM Worldwide Medical & Safety 8

RSV-LRTD, lower respiratory tract disease due to RSV; RSV, respiratory syncytial virus; VE, vaccine efficacy.

Persistent VE against RSV-LRTD with ≥ 3 Symptoms 

through Mid-Season 2

Cumulative Events

RSVpreF 0 1 1 1 2 3 3 4 5

Placebo 0 5 12 15 17 20 24 27 32

40

30

20

10

0

1 74 119 186 235 306 353 417 519

Study Day

Cases

RSVpreF

Placebo
WRDM Worldwide Medical & Safety 9

Persistent VE against RSV-LRTD with ≥ 2 Symptoms 

through Mid-Season 2

Cumulative Events

RSVpreF 0 5 8 10 12 18 24 31 38 38

Placebo 0 13 23 31 40 45 57 72 87 88

100

60

40

20

0

1 64 119 176 233 293 349 404 519

Study Day

467

Cases

80

RSVpreF

Placebo

RSV-LRTD, lower respiratory tract disease due to RSV; RSV, respiratory syncytial virus; VE, vaccine efficacy.
WRDM Worldwide Medical & Safety Confidential 10

Adverse Events, by Category, from Vaccination through 1-Month 

Follow Up Visit and through Data Cutoff (31Jan2023): Safety Population

Adverse Event Category

RSVpreF

N = 18,575

Placebo

N = 18,288

n (%) (95% CI) n (%) (95% CI)

From Vaccination through 1-Month Follow-Up Visit 

Any Event 1,976 (10.6) (10.2, 11.1) 1,897 (10.4) (9.9, 10.8)

Related 259 (1.4) (1.2, 1.6) 178 (1.0) (0.8, 1.1)

Immediate AE 37 (0.2) (0.1, 0.3) 33 (0.2) (0.1, 0.3)

Severe or life-threatening 102 (0.5) (0.4, 0.7) 95 (0.5) (0.4, 0.6)

From Vaccination through 31Jan2023

NDCMC 806 (4.3) (4.1, 4.6) 825 (4.5) (4.2, 4.8)

SAE 790 (4.3) (4.0, 4.6) 746 (4.1) (3.8, 4.4)

Related SAE 3 (<0.1) (0.0, 0.1) 0 (0.0, 0.0)

AE leading to withdrawal 12 (<0.1) (0.0, 0.1) 11 (<0.1) (0.0, 0.1)

AE leading to death 100 (0.5) (0.4, 0.7) 104 (0.6) (0.5, 0.7)

Any reactogenicity reported as adverse events (from either reactogenicity subset or non-reactogenicity subset) during the specified time period are included in this table.

Immediate AE refers to an AE reported in the 30-minute post-vaccination observation period. 

AE, adverse event; NDCMC, newly diagnosed chronic medical condition; SAE, serious adverse event.
WRDM Worldwide Medical & Safety Confidential 11

Adverse Events, by Category, from Vaccination through 1-Month 

Follow Up Visit and through Data Cutoff (31Jan2023): Safety Population

Adverse Event Category

RSVpreF

N = 18,575

Placebo

N = 18,288

n (%) (95% CI) n (%) (95% CI)

From Vaccination through 1-Month Follow-Up Visit 

Any Event 1,976 (10.6) (10.2, 11.1) 1,897 (10.4) (9.9, 10.8)

Related 259 (1.4) (1.2, 1.6) 178 (1.0) (0.8, 1.1)

Immediate AE 37 (0.2) (0.1, 0.3) 33 (0.2) (0.1, 0.3)

Severe or life-threatening 102 (0.5) (0.4, 0.7) 95 (0.5) (0.4, 0.6)

From Vaccination through 31Jan2023

NDCMC 806 (4.3) (4.1, 4.6) 825 (4.5) (4.2, 4.8)

SAE 790 (4.3) (4.0, 4.6) 746 (4.1) (3.8, 4.4)

Related SAE 3 (<0.1) (0.0, 0.1) 0 (0.0, 0.0)

AE leading to withdrawal 12 (<0.1) (0.0, 0.1) 11 (<0.1) (0.0, 0.1)

AE leading to death 100 (0.5) (0.4, 0.7) 104 (0.6) (0.5, 0.7)

Any reactogenicity reported as adverse events (from either reactogenicity subset or non-reactogenicity subset) during the specified time period are included in this table.

Immediate AE refers to an AE reported in the 30-minute post-vaccination observation period. 

AE, adverse event; NDCMC, newly diagnosed chronic medical condition; SAE, serious adverse event.
WRDM Worldwide Medical & Safety 12

RSVpreF/influenza vaccine coadministration study
WRDM Worldwide Medical & Safety 13

Phase 3 Study Design and Key Procedures

RSVpreF/SIIV Coadministration in Adults ≥ 65 Years of Age

• Placebo-controlled, double-blind study

• Assessing safety and immunogenicity 

(non-inferiority)

• Australia (31 sites)

• ~1,400 healthy participants ≥ 65 years of age

• Randomized 1:1

• SIIV: Fluad Quadrivalent

• Timeframe: April 13, 2022 – October 12, 2022

RSVpreF

Placebo

Placebo

RSVpreF

RSVpreF/influenza vaccine 

coadministration

Coadministration Group (n ≈ 700)

Sequential Administration Group (n ≈ 700)

Visit 1 Visit 2 Visit 3

(~ 1 month after Visit 1) (~ 1 month after Visit 2)

SIIV, seasonal inactivated influenza vaccine

SIIV

SIIV
WRDM Worldwide Medical & Safety 14

Coadministration

(RSVpreF + SIIV) / Placebo 

(N = 703)

n (%)

Sequential Administration

(Placebo + SIIV) / RSVpreF 

(N = 696)

n (%)

Total

(N = 1,399)

n (%)

Sex

Female 398 (56.6) 372 (53.4) 770 (55.0)

Age at Visit 1 (years)

Mean (SD) 70.7 (4.7) 70.7 (4.7) 70.7 (4.7)

Median 70.0 70.0 70.0

Min, max (65, 91) (65, 88) (65, 91)

Age group at Visit 1

65-74 years 567 (80.7) 559 (80.3) 1126 (80.5)

≥ 75 years 136 (19.3) 137 (19.7) 273 (19.5)

Race

White 669 (95.2) 665 (95.5) 1,334 (95.4)

Asian 22 (3.1) 21 (3.0) 43 (3.1)

Multiracial 4 (0.6) 1 (0.1) 5 (0.4)

Other 4 (0.6) 4 (0.5) 8 (0.6)

Not reported or unknown 4 (0.6) 5 (0.7) 9 (0.6)

Demographics

RSVpreF/influenza vaccine 

coadministration

SIIV, seasonal inactivated influenza vaccine
WRDM Worldwide Medical & Safety 15

Geometric Mean Ratios with 95% CIs – Evaluable RSV Immunogenicity Population and 

Evaluable SIIV Immunogenicity Population

.

GMRs and 2-sided confidence intervals (CIs) calculated by exponentiating the mean difference of the logarithms of the titers (coadministration minus sequential-administration) and corresponding 

confidence intervals (CIs) (based on Student’s t distribution).

GMR, geometric mean ratio; GMT, geometric mean titer; HAI, hemagglutination inhibition assay; NT, neutralizing titer; RSV, respiratory syncytial virus

Non-inferiority Demonstrated 

by SIIV HAI and RSV Neutralizing Titer GMRs

Comparison, by SIIV/RSV Subgroup GMR (95% CI)

SIIV: HAI: H1N1 A/Victoria 0.86 (0.769, 0.963)

SIIV: HAI: H3N2 A/Darwin 0.77 (0.680, 0.866)

SIIV: HAI: B/Austria 0.90 (0.789, 1.019)

SIIV: HAI: B/Phuket 0.87 (0.779, 0.964)

RSVpreF: NT: RSV A 0.86 (0.785, 0.951)

RSVpreF: NT: RSV B 0.85 (0.766, 0.943)

0.667 1.0 1.5

GMT Ratio

RSVpreF/influenza vaccine 

coadministration
WRDM Worldwide Medical & Safety 16

Similar HAI Titer Seroprotection and Seroconversion at 1 Month 

in Coadministration and Sequential Administration Groups

Coadministration 

(RSVpreF + SIIV)/Placebo

Sequential Administration 

(Placebo + SIIV)/RSVpreF

Serostatus, Strain % (95% CI) % (95% CI)

Seroprotection1

1 month after vaccination

H1N1 A/Victoria 91.6 (89.3, 93.6) 94.3 (92.3, 95.9)

H3N2 A/Darwin 87.9 (85.2, 90.3) 91.0 (88.6, 93.0)

B/Austria 85.3 (82.4, 87.9) 89.5 (87.0, 91.7)

B/Phuket 88.4 (85.7, 90.7) 92.6 (90.4, 94.4)

Seroconversion2

H1N1 A/Victoria 36.6 (32.9, 40.3) 43.9 (40.1, 47.7)

H3N2 A/Darwin 58.8 (55.0, 62.6) 62.6 (58.9, 66.3)

B/Austria 39.5 (35.8, 43.3) 47.3 (43.5, 51.1) 

B/Phuket 25.3 (22.1, 28.8) 28.0 (24.6, 31.5)

1Seroprotection: HAI titer ≥ 1:40

2Seroconversion: ≥ 4-fold rise from before to after receipt of SIIV if the HAI titer is ≥1:10 before SIIV or if the after SIIV HAI titer is ≥ 1:40 where the before SIIV is <1:10

RSVpreF/influenza vaccine 

coadministration
WRDM Worldwide Medical & Safety 17

Participants reporting local reactions by maximum severity within 7 days after each vaccination

Local reactions evaluated on the arm receiving RSVpreF/placebo; no assessment of local reactogenicity at SIIV injection site.

Local reactions after RSVpreF had median onset 2 to 3 days after vaccination and median duration of 1 to 2 days

Only 1 severe local reaction reported (swelling), in the sequential administration group at Visit 2

Local Reactions Mostly Mild or Moderate

0

10

20

30

40

50

60

70

80

90

100

% of Participants

Vaccine as Administered

1.3%

10.1% 0.7%

7.6%

0.9%

6.5%

0.9%

11.5%

0.9%

2.1%

0.1%

0.6%

0.1%

0.3%

0.9%

0.7%

0.9%

2.1%

0%

0.3%

0%

0.1%

0.1%

0.6%

1.2%

RSVpreF/influenza vaccine 

coadministration

Injection Site Pain Redness Swelling

SIIV, seasonal inactivated influenza vaccine
WRDM Worldwide Medical & Safety Confidential 18

Systemic Events Mostly Mild or Moderate

0

10

20

30

40

50

60

70

80

90

100 % of Participants

0.9%

13.7%

15.4%

0.3%

11.3%

15.6%

7.5%

10.1%

0.6%

7.0%

11.5%

0.1%

5.8%

13.7%

0.6%

6.1%

14.3% 0.1%

4.6%

10.4%

0.1%

5.4%

10.6%

0.6%

0.4%

0.1%

0.4%

0.1%

0.3%

0.1%

1.0%

0.4%

2.7%

4.4%

0.3%

1.2%

4.6% 1.0%

3.7%

1.2%

4.2%

2.0%

6.1%

0.1%

1.2%

4.9%1.5%

3.2%

0.3%

1.5%

4.5%

0.1%

5.6%

10.1% 4.8%

7.5% 2.1%

6.9%

0.1%

3.5%

5.8%

0.4%

4.3%

6.8% 3.5%

5.8%

2.2%

5.1%

0.1%

2.8%

4.2%

0.4%

0.3%

1.1%

0.3%

0.3%

0.9%

0.1%

0.7%

0.1%

1.0%

Fatigue Headache Vomiting Nausea Diarrhea Muscle Pain Joint Pain Fever

*Vaccine as Administered

RSVpreF/influenza vaccine 

coadministration

Participants reporting systemic events by maximum severity within 7 days after each vaccination

Systemic events after RSVpreF+SIIV had median onset 2 to 4 days after vaccination and median duration of 1 to 2 days

SIIV, seasonal inactivated influenza vaccine
WRDM Worldwide Medical & Safety 19

Adverse Events, by Category, within One Month 

after Vaccination: Safety Population

RSVpreF/influenza vaccine 

coadministration

Adverse Event Category

RSVpreF+SIIV

(N = 703)

Placebo+SIIV

(N = 695)

Placebo

(N = 689)

RSVpreF

(N = 691)

n (%) n (%) n (%) n (%)

Any event 154 (21.9) 134 (19.3) 117 (17.0) 115 (16.6)

Related 9 (1.3) 3 (0.4) 3 (0.4) 5 (0.7)

Serious 8 (1.1) 6 (0.9) 2 (0.3) 5 (0.7)

Related 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)

Death 0 (0.0) 1 (0.1) 0 (0.0) 0 (0.0)

Immediate 3 (0.4) 1 (0.1) 1 (0.1) 0 (0.0)

Any reactogenicity reported as adverse events (from either reactogenicity subset or non-reactogenicity subset) during the specified time period are included in this table.

Immediate AE refers to an AE reported in the 30-minute post-vaccination observation period. 

AE, adverse event; NDCMC, newly diagnosed chronic medical condition; SAE, serious adverse event; SIIV, seasonal inactivated influenza vaccine.
WRDM Worldwide Medical & Safety Confidential 20

RSVpreF Older Adult Clinical Development Program Updates 

– Conclusions

• Favorable overall safety profile of RSVpreF

• RSVpreF remained efficacious in prevention of 

RSV-LRTD

• Through end of season 1

• In mid-season 2

• Average 13.9 months of follow up since 

vaccination

• RSVpreF safe and well tolerated when 

coadministered with influenza vaccine

• Non-inferior immune responses when 

RSVpreF coadministered with influenza 

vaccine

RENOIR Phase 3 Pivotal Efficacy

– Season 1 and Mid-Season 2

RSVpreF Coadministration with 

Influenza Vaccine
Breakthroughs that change patients’ lives Confidential 21

Thank you