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Breakthroughs that change patients’ lives 1 ConfidentialAlejandra Gurtman, MD, FIDSA
Presentation to ACIPJune 21, 2023RSVpreF Older Adults
Clinical Development Program
Updates
2 Confidential WRDM Worldwide Medical & SafetyABRYSVOTM(Respiratory Syncytial Virus Vaccine)
FDA Approval on 5/31/2023RSVpreF 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
3 Confidential WRDM Worldwide Medical & SafetyRENOIR
–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
4 Confidential WRDM Worldwide Medical & SafetyDay 1 D ay 7 Month 1 Month 6 End Season 1 Start Season 2 End Season 2RENOIR Study Design
Reactogenicity
Subset
(n = 7,169)Local Reactions
Systemic Events
Immunogenicity
Subset
(n = 1,050)All Participants
(N = 36,127) Safety: SAEs, NDCMCsSafety: 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
Day 1 Day 7 Month 1 Month 6 End Season 1 Start Season 2 End Season 2RENOIR Study Design
Reactogenicity
Subset
(n = 7,169)Local Reactions
Systemic Events
Immunogenicity
Subset
(n = 1,050)All Participants
(N = 36,127) Safety: SAEs, NDCMCsSafety: Unsolicited AEs
Weekly active surveillance for acute respiratory symptoms Weekly active surveillance for acute respiratory symptoms
e e
Season 1 Mid-Season 2
5 Confidential WRDM Worldwide Medical & SafetyAE, adverse event; NDCMC, newly diagnosed chronic medical condition; SAE, serious adverse event
Day 1 Day 7 Month 1 Month 6 End Season 1 Start Season 2 End Season 2RENOIR Study Design
Reactogenicity
Subset
(n = 7,169)Local Reactions
Systemic Events
Immunogenicity
Subset
(n = 1,050)All Participants
(N = 36,127) Safety: SAEs, NDCMCsSafety: 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 VaccinationNorthern and Southern Hemispheres Northern Hemisphere
13.9 months
6 Confidential WRDM Worldwide Medical & SafetyAE, adverse event; NDCMC, newly diagnosed chronic medical condition; SAE, serious adverse event
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 4565.1%
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, 2023Number of Events
RSVpreF Placebo
Season 1 (N = 36,127) 2 18
Mid-Season 2 (n = 20,019) 3 1488.9%
78.6%
0 20 40 60 80 100
Vaccine Efficacy (%, 95% CI)RSV-LRTD with ≥ 3 symptoms
7 Confidential WRDM Worldwide Medical & Safety
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 DayCases
RSVpreFPlacebo
8 WRDM Worldwide Medical & SafetyRSV-LRTD, lower respiratory tract disease due to RSV; RSV, respiratory syncytial virus; VE, vaccine efficacy.
9 WRDM Worldwide Medical & SafetyPersistent 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 Day467Cases80
RSVpreFPlacebo
RSV-LRTD, lower respiratory tract disease due to RSV; RSV, respiratory syncytial virus; VE, vaccine efficacy.
10 Confidential WRDM Worldwide Medical & SafetyAdverse Events, by Category, from Vaccination through 1 -Month
Follow Up Visit and through Data Cutoff (31Jan2023): Safety Population
Adverse Event CategoryRSVpreF
N =18,575Placebo
N= 18,288
n(%) (95% CI) n(%) (95% CI)
From Vaccination through 1-Month Fol low-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)
Immed iate AE 37 (0.2) (0.1, 0.3) 33 (0.2) (0.1, 0.3)
Severeor 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)
100 (0.5) (0.4, 0.7) 104 (0.6) (0.5, 0.7) A
E leading to death
Any reactogenicity reported as adverse events (from either reactogenicity subset or non- reactogenicity subset) during the specif ied 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.
11 Confidential WRDM Worl dwide Medical & SafetyAdverse Events, by Category, from Vaccination through 1 -Month
Follow Up Visit and through Data Cutoff (31Jan2023): Safety Population
Adverse Event CategoryRSVpr
eF
N =18,575Placebo
N= 18,288
n(%) (95% CI) n(%) (95% CI)
From Vaccinati on 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 Vaccinati on 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 wi thdrawal 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 specif ied 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.
12 WRDM Worldwide Medical & SafetyRSVpreF/influenza vaccine coadministration study
13 WRDM Worldwide Medical & SafetyPhase 3 Study Design and Key ProceduresRSVpreF/SIIV Coadministration in Adults ≥ 65 Years of Age
•Placebo-controlled, double-blind study
•Assessing safety and immunogenicity
(non- i
nferiority)
•Australia (31 sites)
•~1,400 healthy participants ≥ 65 years of age
•Randomized 1:1
•SIIV: Fluad Quadrivalent
•Tim
eframe: April 13, 2022 –October 12, 2022RSVpreF
Placebo
Placebo
RSVpreFRSVpreF/influenza vaccine
coadministration
Coadministration Group (n ≈ 700)
Sequential Administration Group (n ≈ 700)Visit 3 Visit 2 Visit 1
(~ 1 month after Visit 2) (~ 1 month after Visit 1)
SIIV, seasonal inactivated influenza vaccineSIIV
SIIV
14 WRDM Worldwide Medical & SafetyCoadministration
(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)DemographicsRSVpreF/influenza vaccine
coadministration
SIIV, seasonal inactivated influenza vaccine
WRDM Worldwide Medical & Safety 15Geometric 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, respi ratory syncytial virusNon-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 RatioRSVpreF/influenza vaccine
coadministration
16 WRDM Worldwide Medical & SafetySimilar HAI Titer Seroprotection and Seroconversion at 1 Month
in Coadministration and Sequential Administration Groups
Coadministration
(RSVpreF + SIIV)/PlaceboSequential 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 <1:10RSVpreF/influenza vaccine
coadministration
17 WRDM Worldwide Medical & SafetyParticipants reporting local reactions by maximum severity within 7 days after each vaccination0102030405060708090100
Vaccine as Administered1.3%
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%Injection Site Pain Redness Swelling
% of Participants
Local r
eactions 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 2Local Reactions Mostly Mild or ModerateRSVpreF/influenza vaccine
coadministration
SIIV, seasonal inactivated influenza vaccine
18 Confidential WRDM Worldwide Medical & SafetySystemic Events Mostly Mild or Moderate
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 Fever Headache Vomiting Nausea Diarrhea Muscle Pain Joint Pain
*Vaccine as Administered100
90
80s70pant60ci i t
50ar P of
40 %
302010
0
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
19 WRDM Worldwide Medical & SafetyAdverse Events, by Category, within One Month
after Vaccination: Safety PopulationRSVpreF/influenza vaccine
coadministration
Adverse Event CategoryRSVpreF+SIIV
(N = 703)Placeb o+SIIV
(N = 695)Placeb o
(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 specif ied 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 i nfluenza vaccine.
20 Confidential WRDM Worldwide Medical & SafetyRSVpreF 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
vaccineRENOIR Phase 3 Pivotal Efficacy
–Season 1 and Mid -Season 2RSVpreF Coadministration with
Influenza Vaccine
21 Confidential Breakthroughs that change patients’ livesThank you