Document text
CO-1
Meeting of the Advisory Committee on
Immunization Practices (ACIP)
Centers for Disease Control and Prevention
April 16, 2025
Susan Gerber, MD
Medical Director
GSK
Presentation by GSK at ACIP April 16, 2025
CO-2
AREXVY Indications and Updates
AREXVY is indicated for active immunization for prevention of lower respiratory tract disease
(LRTD) caused by RSV in
▪Individuals ≥ 60 YOA
▪Individuals 50-59 YOA at increased risk for LRTD caused by RSV
~ 11 million AREXVY doses administered in US through March *
*Up to March 2025; YOA, years of age; LRTD: lower respiratory tract disease
FDA, 2024. AREXVY Prescribing Information (PI); https://www.fda.gov/media/167805/download (URL accessed January 2025) Presentation by GSK at ACIP April 16, 2025
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Clinical Development
Presentation by GSK at ACIP April 16, 2025
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Key Studies in Current US Clinical Development Plan
Pivotal efficacy
in ≥ 60 YOASafety, immunogenicity,
persistence and
revaccination
in ≥ 60 YOA Co-administration7–12
Immunogenicity &
safety in 50 -59 YOA
(incl. AIR)Immunogenicity &
safety in
18-49 YOA AIRImmunogenicity &
safety in
Immunocompromised
≥ 18 YOA
(lung and kidney SOT)▪AReSVi -006
▪Complete▪RSV OA=ADJ -012
▪Ongoing
▪Extension of AReSVi -006Safety, immunogenicity,
persistence and
revaccination
in ≥ 60 YOA
▪AReSVi -004
▪Ongoing▪COVID -19 mRNA vaccine
(RSV OA=ADJ -013; Ongoing)
▪PCV20 (RSV OA=ADJ -019; Complete )
▪HZ/su (RSV OA=ADJ -020; Complete )
▪FLU-QIV (RSV OA=ADJ -007; Complete )
▪FLU-aQIV (RSV OA=ADJ -017; Complete )
▪FLU-QIV-HD (RSV OA=ADJ -008; Complete )
▪RSV OA=ADJ -018
▪Complete▪RSV OA=ADJ -025
▪Ongoing
▪RSV OA=ADJ -023
▪OngoingPhase 2b Phase 3
AIR, at increased risk; FLU -aQIV , adjuvanted quadrivalent influenza vaccine; FLU -QIV, quadrivalent influenza vaccine; FLU -QIV-HD, high -dose quadrivalent influen za vaccine;
HZ/su, herpes zoster recombinant subunit vaccine; PCV20, 20 -valent pneumococcal conjugate vaccine;
SOT, solid organ transplant; YOA, years of age; All studies ClinicalTrials.gov; All URLs accessed February 2025 Presentation by GSK at ACIP April 16, 2025
CO-5
Immunogenicity of AREXVY in Adults ≥ 60 YOA Evaluated in
Two Complementary Trials
AReSVi -006 RSV 1 Dose
(N=12,468)
AReSVi -006 Placebo
Crossover (N=12,498)M48 Revaccination (N≈1,000)Timepoint D1 M13 M24 M25 M60 M12 M36 M37 M48 M49Final End of
Study analysisRSV OA=ADJ -012 AReSVi -004Completed
RSV 1 Dose (N≈330)
RSV M12, M24
Revaccination (N≈990)
RSV M24 Revaccination
(N≈330)R RSV 1 dose (N≈1,000) AReSVi -006
Crossover F irst Dose RSVPreF3 + AS01E (N≈6,600)
All studies available on clinicaltrials.gov; All URLs accessed April 2025. Presentation by GSK at ACIP April 16, 2025All participants followed for safety
RSVPreF3 + AS01E
PlaceboAReSVi -004 / RSV OA=ADJ -012
R M36 Revaccination (N≈1,000)
RSV M36 revaccination (N≈100)
RSV 1 dose (N≈125)D31
CO-6
AReSVi -004: Immunogenicity and Persistence of Single
Dose of AREXVY Vaccine and Different Revaccination
Schedules in Adults ≥ 60 YOA
Randomized, open -label, multi -country study (NCT04732871)
Preliminary updated results
Presentation by GSK at ACIP April 16, 2025
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RSV-A and RSV -B Neutralizing Antibody Titers After
12-, 24-, and 36 -Month Vaccination Intervals
RSV M12, M24 Revaccination RSV M24 Revaccination RSV 1 Dose RSV M36 Revaccination
1000.010000.0
GMT (ED60)
[95%CI]
M
6M
12M
18M
24M
25M
13D
31D
1M
36M
37M
301000.010000.0
M
6M
12M
18M
24M
25M
13D
31D
1M
36M
37M
30
Timepoint TimepointGMT (ED60)
[95%CI]RSV-A Serum Neutralization Titers RSV-B Serum Neutralization Titers
RSV 1 dose (N=112 -121): Participants receiving single dose (Dose 1) of RSVPreF3 + AS01E at Day 1; RSV M12, M24 revaccination (N=247 -341): Participants receiving first dose (Dose 1) of RSVPreF3 +
AS01E at Day 1, followed by revaccination doses at 12 months and 24 months post Dose 1; RSV M24 revaccination (N=223 -318): Participan ts receiving first dose (Dose 1) of RSVPreF3 + AS01E at Day 1
followed by revaccination dose at 24 months post Dose 1; RSV M36 Revaccination (N=98 -107): Participants receiving first dose (Do se 1) of RSVPreF3 + AS01E at Day 1, followed by revaccination dose
at 36 months post Dose 1. ED, estimated dilution; GMT, geometric mean titerAReSVi -004
Presentation by GSK at ACIP April 16, 2025
CO-8
RSVPreF3 -Specific CD4+ T -Cells*: Consistent Responses
Post Each Vaccination Dose
RSVPreF3
CD4+ T-cells, /106 cells
(geometric mean [95% CI])
0.0500.01000.01500.02000.02500.03000.0
M
6M
12M
18M
24M
25M
13D
31D
1M
36M
37M
30
Timepoint
*Expressing ≥ 2 activation markers including ≥ 1 cytokine among CD40L, 4 -1BB, IL -2, TNF -a, IFN -g, IL-13, IL -17; RSV 1 dose (N=31 -42): Participants receiving single dose (Dose 1) of RSVPreF3 + AS01E
at Day 1; RSV M12, M24 revaccination (N=215 -286): Participants receiving first dose (Dose 1) of RSVPreF3 + AS01E at Day 1, followed by revaccination doses at 12 months and 24 months post Dose 1;
RSV M24 revaccination (N=68 -88): Participants receiving first dose (Dose 1) of RSVPreF3 + AS01E at Day 1 followed by revaccination dose at 24 months post Dose 1; RSV M36 Revaccination (N=31 -
37): Participants receiving first dose (Dose 1) of RSVPreF3 + AS01E at Day 1, followed by revaccination dose at 36 months post Dose 1.
CD, cluster of differentiation; IL, interleukin; NAb, neutralizing antibody; TNF, tumor necrosis factorAReSVi -004
RSV M12, M24 Revaccination RSV M24 Revaccination RSV 1 Dose RSV M36 Revaccination
Presentation by GSK at ACIP April 16, 2025
CO-9
RSV OA=ADJ -012: I mmunogenicity of Different Revaccination
Schedules and Persistence of a Single Dose of AREXVY Vaccine
in Adults Aged ≥ 60 YOA Who Participated in Pivotal AReSVi -006
Efficacy Study
Open -label extension and crossover study (NCT06534892)
Preliminary results
Presentation by GSK at ACIP April 16, 2025
CO-10
RSV-A and RSV -B NAb Titers After Initial Dose and 36 -Month
Revaccination Similar Regardless of Comorbidities of Interest*
100100010000
GMT
(ED60)
[95%CI]
\
100100010000
\M
12M
24D
31M
36M
37
TimepointM
12M
24D
31D
1M
36M
37
Timepoint≥1 comorbidity of interest* Overall No comorbidity
*COPD, asthma, any chronic respiratory/pulmonary disease, diabetes type 1 or type 2, chronic heart failure, advanced liver or renal disease; ED, estimated dilution; GMT, geometric mean titer; NAb,
neutralizing antibody; 1. Unpublished data; 2. Feldman RG et al. Clin Infect Dis 2024; Day 1 to M12: All participants who received one dose of RSVPreF3 + AS01E in AReSVi -006 ( Immunosubset ); M24:
All participants randomized into RSV_1dose group ( Immunosubset ) in AReSVi -006 who did not receive additional doses of vaccine;
M36 - M37: All participants who received second dose of RSVPreF3 + AS01E approximately 36 Months post -primary dose Presentation by GSK at ACIP April 16, 2025RSV-A Serum Neutralization Titers RSV-B Serum Neutralization Titers
GMT
(ED60)
[95%CI]AReSVi -006 / RSV OA=ADJ -012
544
328519
315416
246180
94552
412535
379
872 834 662 274 964 914No comorbidity (n)
≥ 1 comorbidity (n)
Overall (n)544 519 417 180 552 535
328 315 246 94 412 379
872 834 663 274 964 914D
1
CO-11
100100010000
100100010000RSV-A and RSV -B NAb Titers After Initial Dose and 36 -Month
Revaccination Similar Regardless of Frailty Status
\M
12M
24D
31D
1M
36M
37\M
12M
24D
31D
1M
36M
37
ED, estimated dilution; GMT, geometric mean titer; NAb, neutralizing antibody; Unpublished data; Day 1 to M12: All participants who received one dose of adjuvanted RSVPreF3 vaccine in RSV
OA=ADJ -006 ( Immunosubset ); M24: All participants randomized into the RSV_1dose group ( Immunosubset ) in RSV OA=ADJ -006 who did not receive additional doses of vaccine;
M36 - M37: All participants who received a second dose of adjuvanted RSVPreF3 vaccine approximately 36 Months post -primary doseRSV-A Serum Neutralization Titers RSV-B Serum Neutralization Titers
GMT
(ED60)
[95%CI]GMT
(ED60)
[95%CI]Overall Frail Pre-frail Fit
Timepoint Timepoint16
38214
35515
2875
11121
39719
374
474 465 360 158 541 516Frail (n)
Pre-frail (n)
Fit (n)
872 834 662 274 964 914 Overall (n)16 14 15 5 21 19
382 355 287 111 397 374
361 158 541 516 474 465
872 834 663 274 964 914AReSVi -006 / RSV OA=ADJ -012
Presentation by GSK at ACIP April 16, 2025
CO-12
Increase in RSV -A and RSV -B NAb Titers Following Revaccination
with AREXVY at 36 Months Across Pre -Revaccination Levels
110100100010000100000Pre-revaccination
(Month 36 )Post-revaccination
(Month 37 )
1 2 3
Quartile*
N 225 227 226 2264110100100010000100000
1 2 3
Quartile*
N 226 226 226 2264
*Participants grouped into quartiles depending on pre -revaccination NAb titers . Participants in quartile 1 had lowest pre -revaccination NAb and those in quartile 4 had highest;
Participants receiving first dose (Dose 1) of RSVPreF3 + AS01E at Day 1 (in AReSVi -006 study) followed by revaccination
dose at 36 months post Dose 1 (in RSV OA=ADJ -012 study); ED, estimated dilution; GMT, geometric mean titer; NAb, neutralizing antibody
Unpublished data Presentation by GSK at ACIP April 16, 2025RSV-A Serum Neutralization Titers RSV-B Serum Neutralization TitersRSV OA=ADJ -012
4.9 3.1 2.3 1.5Fold increase
(by GMTs)
GMT
(ED60)
[95%CI]GMT
(ED60)
[95%CI]4.7 2.9 2.5 1.6Fold increase
(by GMTs)
CO-13
Lower Pre -Revaccination RSV -A and RSV -B NAb Titers
Associated with Higher Seroresponse Rates (≥ 4 -Fold Increase)
After Revaccination at 36 Months
Participants with
≥ 4-fold increase in
RSV-B NAb titers at
M37 vs M36
[95% CI]
0%20%40%60%80%100%
0 1 2 3 422.6
(17.3, 28.6)
8.8
(5.5, 13.3)29.6
(23.8, 36.1)52.7
(45.9, 59.3)
1 2 3 4
Quartile*Participants with
≥ 4-fold increase in
RSV-A NAb titers at
M37 vs M36
[95% CI]
0%20%40%60%80%100%
0 1 2 3 418.1
(13.3, 23.8)
7.5
(4.4, 11.8)33.9
(27.8, 40.5)56.9
(50.1, 63.5)
1 2 3 4
Quartile*
n / N 128 / 225 77 / 227 41 / 226 17 / 226RSV OA=ADJ -012
*Participants grouped into quartiles depending on pre -revaccination NAb titers . Participants in quartile 1 had lowest pre -revaccination NAb and those in quartile 4 had highest;
Participants receiving first dose (Dose 1) of RSVPreF3 + AS01E at Day 1 (in AReSVi -006 study) followed by revaccination
dose at 36 months post Dose 1 (in RSV OA=ADJ -012 study); NAb, neutralizing antibody Presentation by GSK at ACIP April 16, 2025RSV-A Serum Neutralization Titers RSV-B Serum Neutralization Titers
n / N 119 / 226 67 / 226 51 / 226 20 / 226
CO-14
AReSVi -004 and RSV OA=ADJ -012: Safety Results
Preliminary updated results
Presentation by GSK at ACIP April 16, 2025
CO-15
0%20%40%60%80%100%Safety and Reactogenicity Profile in Individuals Revaccinated
at Month 36 Similar to First Dose
Solicited AEs reported within 4 days of each vaccine dose (Exposed Set)
% of
Participants
[95% CI]Grade 3
Arthralgia Fatigue Fever Headache Myalgia Erythema Pain Swelling
Unsolicited AEs, SAEs, Fatal SAEs and pIMDs of individuals who were revaccinated at Month 36 also similar to those vaccinated at Day 1LocalRSV M36 Revaccination
(Day 1 Dose)RSV M36 Revaccination
(M36 Dose)
4.615.164.8
57.5
2.87.514.817.932.434.0
1.93.821.3 20.832.435.8M36 Revac
(Day 1)
M36 Revac
(M36)
M36 Revac
(Day 1)
M36 Revac
(M36)
M36 Revac
(Day 1)
M36 Revac
(M36)
M36 Revac
(Day 1)
M36 Revac
(M36)
M36 Revac
(Day 1)
M36 Revac
(M36)
M36 Revac
(Day 1)
M36 Revac
(M36)
M36 Revac
(Day 1)
M36 Revac
(M36)
M36 Revac
(Day 1)
M36 Revac
(M36)AReSVi -004
RSV 36M revaccination: Participants receiving the first dose (Day 1 Dose) of RSVPreF3 + AS01E at Day 1 followed by a revaccination dose at 36 months (M36 Dose) post -Dose 1.
Grade 3: >100 mm for erythema and swelling; significant pain at rest, prevents normal everyday activities for pain; prevents normal activity for headache, fatigue, myalgia,
and arthralgia; >39.0 °C (102.2 °F) for fever. AE, adverse event; SAE, serious adverse event; pIMD , potential immune -mediated diseaseSystemic
Presentation by GSK at ACIP April 16, 2025
CO-16
39.3
31.7
2.235.5
27.9
2.3
0%20%40%60%80%100%
▪Safety profile after revaccination of AREXVY acceptable and consistent with first dose in RSV OA=ADJ -012
▪No events of GBS or ADEM reported in RSV OA=ADJ -012Safety Profile of Revaccination at Month 36 Similar to
First -Vaccination Dose in Crossover Group RSV OA=ADJ -012
Presentation by GSK at ACIP April 16, 2025Grade 3
Any unsolicited AE within
30 days post -vaccinationM36 Revaccination
(N = 993)Crossover
First Dose RSVPreF3 + AS01E
(N = 6,638)
Any vaccine -related unsolicited AE
within 30 days post -vaccinationAny SAE up to 6 months
post -vaccinationParticipants
Reporting
Event
(95% CI)
*Solicited AEs not collected in RSV OA=ADJ -012
CO-17
Summary: AReSVi -004 and RSV OA=ADJ -012
Robust humoral and cellular immune responses observed with AREXVY revaccination
▪Humoral immune responses similar among participants with ≥ 1 comorbidity of interest or
frailty status compared to overall population
▪RSV neutralizing antibody responses observed after revaccination at 36 -month interval
similar to RSV neutralizing antibody responses after revaccination at 24 -month interval
▪The lower the pre -revaccination RSV -A and RSV -B neutralizing titers, the higher the
seroresponse rates after revaccination at 36 months
Safety and reactogenicity of revaccination is similar as compared with first dose
Presentation by GSK at ACIP April 16, 2025
CO-18
224403757
0100200300400500600700800
RSV-Related DeathsRSV Outcomes Estimated to be Avoided with Vaccination vs
No Vaccination Over 3 Years Based on Vaccine Efficacy Results
from AReSVi -006 (30.6 -Month Median Follow Up)
3,1835,7369,838
02,0004,0006,0008,00010,00012,000
RSV-Related Hospitalizations
Presentation by GSK at ACIP April 16, 2025Estimates are based on GSK modeling that synthesized multiple published and public sources, and involved assumptions to infor m certain parameters, including variability in RSV -related mortality
by age. Key references for model inputs include: Singer et al., Poster Presentation at RSV Symposium 2025; La et al., Human V accines & Immunotherapeutics , 2024; Branche et al., Clin Infect Dis,
2022; McLaughlin et al., Open Forum Infect Dis, 2022; Tseng et al., J Infect Dis, 2020 ; Ison et al., Poster Presentation at CHEST 2024 .
COPD = chronic obstructive pulmonary disease; YOA = years of ageDiabetes COPD Heart Failure
Estimated RSV
Outcomes
Avoided
per 1 Million
AREXVY
Vaccinations
Among Adults
50-59 YOA
CO-19
Conclusion
Presentation by GSK at ACIP April 16, 2025
Real world vaccine effectiveness data, along with ongoing immunogenicity studies,
will inform optimal revaccination timing
~13 million US adults 50 -59 YOA at risk for severe RSV disease
▪Over 3 years, vaccination with AREXVY* may help prevent an estimated
▪~3,218 hospitalizations in individuals with heart failure
▪~8,638 hospitalizations in individuals with COPD
▪~8,164 hospitalizations in individuals with diabetes
Evidence to support revaccination with AREXVY
▪Robust humoral and cellular immune responses following revaccination at
24 and 36 -month intervals
▪Lower pre -revaccination titers elicit higher seroresponse rates after revaccination
▪Safety and reactogenicity of revaccination is similar as compared with first dose
*Based on GSK modeling 46.2% uptake = flu vaccine uptake in group
CO-20
Meeting of the Advisory Committee on
Immunization Practices (ACIP)
Centers for Disease Control and Prevention
April 16, 2025
Susan Gerber, MD
Medical Director
GSK
Presentation by GSK at ACIP April 16, 2025
CO-21
•AREXVY is contraindicated in anyone with a history of a severe allergic reaction ( eg, anaphylaxis) to any
component of AREXVY
•The results of a postmarketing observational study suggest an increased risk of Guillain -Barré syndrome during the
42 days following vaccination with AREXVY
•Appropriate medical treatment must be immediately available to manage potential anaphylactic reactions following
administration of AREXVY
•Syncope (fainting) may occur in association with administration of injectable vaccines, including AREXVY .
Procedures should be in place to avoid injury from fainting
•Immunocompromised persons, including those receiving immunosuppressive therapy, may have a diminished
immune response to AREXVY
•In adults 60 years of age and older, the most commonly reported adverse reactions (≥10%) were injection site pain
(60.9%), fatigue (33.6%), myalgia (28.9%), headache (27.2%), and arthralgia (18.1%)
•In adults 50 through 59 years of age, the most commonly reported adverse reactions (≥10%) were injection site pain
(75.8%), fatigue (39.8%), myalgia (35.6%), headache (31.7%), arthralgia (23.4%), erythema (13.2%), and swelling
(10.4%)
•There are no data on the use of AREXVY in pregnant or breastfeeding individuals. AREXVY is not approved for use
in persons <50 years of age
•Vaccination with AREXVY may not result in protection of all vaccine recipientsAREXVY Important Safety InformationAREXVY Indication
AREXVY is a vaccine indicated for 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;
•individuals 50 through 59 years of age who are at increased risk for LRTD caused by RSV