Document text
CO-1
Meeting of the Advisory Committee on
Immunization Practices (ACIP)
Centers for Disease Control and Prevention
October 24, 2024
Susan Gerber, MD
Medical Director
GSK
Presentation by GSK at ACIP October 24, 2024
CO-2
~ 9 million AREXVY doses administered in US to dateAREXVY Indications
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
YOA, years of age
FDA, 2024. AREXVY Prescribing Information (PI); https://www.fda.gov/media/167805/download (URL accessed Aug 2024)
CO-3
RSV- OA=ADJ -023: Immune response and safety among adult
lung and kidney transplant recipients ≥ 18 years of age
Preliminary results
A Phase 2b, randomized, controlled, open- label study to evaluate the immune response
and safety of the RSVPreF3 + AS01E vaccine in adults (≥18 years of age) when
administered to lung and kidney transplant recipients comparing a 1 versus a 2- dose
schedule and compared to adults (≥50 years of age) receiving 1 dose
NCT 05921903
CO-4
RSV- OA=ADJ -023: Phase 2b Study Design
Descriptive immunogenicity and safety study in lung and kidney transplant recipients ≥ 18 YOA versus adults ≥ 50 YOA
1-dose; n=125Study initiation:
July 2023Visit 2*
7–14 days
post-Dose 1Visit 3
1 month***
post-Dose 1
Cohort 1
Adults with
SOT ≥ 18 YOA
N=261
1-dose; n=131
Lung SOT, n=39
Kidney SOT, n=92
2-dose; n=130
Lung SOT, n=36
Kidney SOT, n=94Visit 4
1 month
post-Dose 2****Visit 6
12 months
post-last doseVisit 5
6 months
post-last doseVisit 1
Day 1
Safety
analysesSolicited AEs Within 7 days of a vaccine dose
Unsolicited AEs Within 30 days of a vaccine dose
SAEs, pIMDs , and AESIs related to transplantation Up to end of studyCurrent analysis
Adults
≥ 50 YOA
N=125
*Only in subset of study population, ~30% of participants; **Blood sample for CMI analysis collected at each visit only in su bset of study population (~30% of participants);
***Allowed interval range: 30 -60 days; ****For Adults with SOT 1 -dose group and Adults ≥ 50 YOA, Visit 4 refers to 1 -month post- Visit 3; AE, adverse event; AESI, adverse event of special interest;
CMI, cell- mediated immunity; HI, humoral immunity; pIMD , potential immune -mediated disorder; SAE, serious adverse event; SOT, solid organ transplant; YOA, years of ageRSVPreF3 + AS01E
Blood sample; HI, CMI**Cohort 2RSV-OA=ADJ -023
R
1:1
CO-5
Key Inclusion and Exclusion Criteria
Adults with SOT (kidney & lung) ≥ 18 YOA
Inclusion criteria:
ABO compatible allogeneic kidney or lung transplant (allograft)
> 12 months prior to first study intervention
Receiving maintenance immunosuppressive therapy for prevention of allograft rejection
Exclusion criteria:
Allograft rejection in 3 months prior to first dose
Current diagnosis of malignancy
Use of anti -CD20 or other B -cell mAb agents for prevention of allograft
rejection within 9 months of first doseInclusion criteria: Stable lung function
Exclusion criteria:
•Acute pulmonary infection with 2 weeks of study intervention visit
•Diagnosis of chronic lung allograft dysfunction LungInclusion criteria: Stable renal function
Exclusion criteria:
•Previous allograft loss secondary to recurrent primary kidney disease
•Significant proteinuria/albuminuriaKidney
Inclusion criteria:
Medically stable in investigator’s opinion
Participants with chronic stable conditions with or without specific treatment (e.g., diabetes mellitus, hypertension, cardiac disease)
Exclusion criteria:
Immunosuppressive or immunodeficient conditions
Unstable chronic illnessAdults ≥ 50 YOA
ABO, ABO blood group system; CD, cluster of differentiation; mAb , monoclonal antibody; SOT, solid organ transplant; YOA, years of age
ClinicalTrials.gov. NCT05921803. https://www.clinicaltrials.gov/study/NCT05921903 (accessed September 2024)RSV-OA=ADJ -023
CO-6
Demographic Characteristics Generally Balanced Between Groups
(Exposed Set)
CharacteristicAdults with SOT ≥ 18 YOA Adults ≥ 50 YOA
Total
(N=386)1-dose group
(N=131)2-dose group
(N=130)1-dose group
(N=125)
Age (years) at vaccination, mean (SD) 61.9 (9.3) 61.4 (8.4) 63.8 (8.2) 62.4 (8.7)
Age category, n (%)
18–49 YOA 9 (6.9) 8 (6.2) 0 (0.0) 17 (4.4)
50–59 YOA 37 (28.2) 41 (31.5) 44 (35.2) 122 (31.6)
≥ 60 YOA 85 (64.9) 81 (62.3) 81 (64.8) 247 (64.0)
Sex, n (%)
Female 54 (41.2) 50 (38.5) 66 (52.8) 170 (44.0)
Ethnicity, n (%)
Hispanic or Latino 12 (9.2) 5 (3.8) 22 (17.6) 39 (10.1)
Race, n (%)
American Indian or Alaska Native 0 (0.0) 1 (0.8) 0 (0.0) 1 (0.3)
Asian 26 (19.8) 33 (25.4) 10 (8.0) 69 (17.9)
Black or African American 11 (8.4) 8 (6.2) 4 (3.2) 23 (6.0)
White 89 (67.9) 79 (60.8) 95 (76.0) 263 (68.1)
Not reported or unknown 4 (3.1) 9 (6.9) 15 (12.0) 28 (7.3)
Multiple 1 (0.8) 0 (0.0) 1 (0.8) 2 (0.5)
SOT type, n (%)
Lung transplant 39 (29.8) 36 (27.7) - -
Kidney transplant 92 (70.2) 94 (72.3) - -
Interval between last transplantation and Visit 1
(months), median (min, max) 67 (12, 386) 60 (14, 450) - -RSV-OA=ADJ -023
Adults with SOT 1 -dose group: adults with kidney and lung transplant ≥18 YOA receiving 1 dose of RSVPreF3 + AS01E at Visit 1 (Day 1); Adults with SOT 2 -dose group: adults with kidney and lung
transplant ≥18 YOA receiving 2 doses of RSVPreF3 + AS01E at Visit 1 (Day 1) and Visit 3 (30– 60 days post -Dose 1); Adults ≥50 YOA group: adults ≥50 YOA receiving 1 dose of RSVPreF3 + AS 01E at
Visit 1 (Day 1); SD, standard deviation; SOT, solid organ transplant; YOA, years of age
CO-7
Worldwide Study Including 8 Countries
Canada (n=47)
Australia (n=26)
Japan (n=61)
Italy (n=28)
Germany (n=14)
United States (n=104)
Adults with SOT
≥ 18 YOAAdults
≥ 50 YOA
1-dose
group2-dose
group 1-dose
group
n (%) 39 (29.8) 33 (25.4) 32 (25.6)
SOT type, n (%)
Lung 10 (25.6) 8 (22.2) -
Kidney 29 (31.5) 25 (26.6) -
Spain (n=82)RSV-OA=ADJ -023
South Korea
(n=24)
CO-8
Immunogenicity
Preliminary results
CO-9
Co-primary Endpoints: RSV -A and RSV -B NAbs Higher at
1 Month Post -Dose 2 vs Post- Dose 1 in Adults with SOT ≥ 18 YOA
Receiving 2 Doses of RSVPreF3 + AS01E*
NRSV-A NAb titers expressed as
MGI ratio MGI ratio (95% CI)
111 1.34 (1.20, 1.48)MGI =1 month post−Dose 2 (Visit 4)
1 month post−Dose 1 (Visit 3)
RSV-A
MGI =1 month post−Dose 2 (Visit 4)
1 month post−Dose 1 (Visit 3)
RSV-B0.5 1.0 1.5 2.0
NRSV-B NAb titers expressed as
MGI ratio MGI ratio (95% CI)
111 1.26 (1.14, 1.40)
0.5 1.0 1.5 2.0
*Adults with SOT ≥ 18 YOA receiving 2 doses of RSVPreF3 + AS01E at Visit 1 (Day 1) and Visit 3 (30– 60 days post -Dose 1)
CI, confidence interval; MGI, mean geometric increase; NAb, neutralizing antibody; SOT, solid organ transplant; YOA, years of ageRSV-OA=ADJ -023
CO-10
RSVPreF3 + AS01E Elicits Robust Humoral Immune
Responses in Kidney and Lung Transplant Recipients
SOT 1 -dose 114 114 114
SOT 2 -dose 110 110 110
≥ 50 YOA 105 105 105GMT,
ED60
(95% CI)
5005000
GMT,
ED60
(95% CI)
Visit 3
1 month
post-Dose 1Visit 1 Visit 4
1 month
post-Dose 2**5005000
0 0.5 1 1.5 2
SOT 1 -dose 114 114 114
SOT 2 -dose 110 110 110
≥ 50 YOA 105 105 105Visit 4
1 month
post-Dose 2**Visit 1 Visit 3
1 month
post-Dose 1
*In participants with results available at all timepoints; **For Adults with SOT 1 -dose group and Adults ≥50 YOA, Visit 4 refers to 1 month post- Visit 3
Adults with SOT 1 -dose group: adults with kidney and lung transplant ≥18 YOA receiving 1 dose of RSVPreF3 + AS01E at Visit 1 (Day 1); Adults with SOT 2 -dose group: adults with kidney and lung
transplant ≥18 YOA receiving 2 doses of RSVPreF3 + AS01E at Visit 1 (Day 1) and Visit 3 (30– 60 days post -Dose 1); Adults ≥50 YOA group: adults ≥50 YOA receiving 1 dose of RSVPreF3 + AS 01E at
Visit 1 (Day 1); CI, confidence interval; ED60, estimated dilution 60; GMT, geometric mean titer; NAb, neutralizing antibody; SOT, solid organ transplant; YOA, years of ageRSV-OA=ADJ -023
RSV-A NAbs * RSV-B NAbs *
Adults with SOT ≥ 18 YOA
1-doseAdults with SOT ≥ 18 YOA 2-doseAdults ≥ 50 YOAn n
CO-11
5005000
5005000
5005000
5005000
5005000
5005000RSVPreF3 + AS01E Induced Similar RSV -A and RSV -B Neutralizing
Antibody Responses in Kidney and Lung Transplant Recipients
GMT,
ED60
(95% CI)
Visit 3
1 month
post-Dose 1Visit 1 Visit 4
1 month
post-Dose 2*
Kidney 1 dose 89 88 83
Kidney 2 dose 90 84 81
Lung 1 dose 34 35 33
Lung 2 dose 33 30 30Visit 3
1 month
post-Dose 1Visit 1 Visit 4
1 month
post-Dose 2*GMT,
ED60
(95% CI)
*For Adults with SOT 1 -dose group, Visit 4 refers to 1 month post- Visit 3; Adults with SOT 1 -dose group: adults with kidney and lung transplant ≥18 YOA receiving 1 dose of RSVPreF3 + AS01E at Visit
1 (Day 1); Adults with SOT 2 -dose group: adults with kidney and lung transplant ≥18 YOA receiving 2 doses of RSVPreF3 + AS01E at Visit 1 (Day 1) and Visit 3
(30–60 days post -Dose 1);CI, confidence interval; ED60, estimated dilution 60; GMT, geometric mean titer; SOT, solid organ transplant; YOA, years of ageRSV-OA=ADJ -023
RSV-A NAbs RSV-B NAbs
1 dose 2 doseKidney transplant
1 dose 2 doseLung transplantKidney 1 dose 89 88 83
Kidney 2 dose 90 84 81
Lung 1 dose 34 35 33
Lung 2 dose 33 30 30n n
CO-12
SOT
1-doseMC 94 94 88
No MC 29 29 28
SOT
2-doseMC 93 89 87
No MC 30 25 24
≥ 50 YOA 125 118 1105005000
5005000
5005000
SOT
1-doseMC 94 94 88
No MC 29 29 28
SOT
2-doseMC 93 89 87
No MC 30 25 24
≥ 50 YOA 125 118 1105005000
5005000
5005000Differences in RSV -A and RSV -B Neutralizing Antibody Responses
Induced by RSVPreF3 + AS01E by Presence or Absence of Mycophenolate
GMT,
ED60
(95% CI)GMT, ED60
(95% CI)
Visit 1 Visit 4
1 month
post-Dose 2*Visit 3
1 month
post-Dose 1Visit 1 Visit 4
1 month
post-Dose 2 *Visit 3
1 month
post-Dose 1
*For Adults with SOT 1 -dose group and Adults ≥50 YOA, Visit 4 refers to 1 month post- Visit 3; Adults with SOT 1 -dose group: adults with kidney and lung transplant ≥18 YOA receiving 1 dose of
RSVPreF3 + AS01E at Visit 1 (Day 1); Adults with SOT 2 -dose group: adults with kidney and lung transplant ≥18 YOA receiving 2 doses of RSVPreF3 + AS01E at Visit 1 (Day 1) and Visit 3 (30– 60 days
post- Dose 1); CI, confidence interval; ED60, estimated dilution 60; GMT, geometric mean titer; MC, mycophenolate; SOT, solid organ transplant; YOA, years of ageRSV-OA=ADJ -023
RSV-A NAbs RSV-B NAbs
MC No MCAdults with SOT ≥ 18 YOA
1-dose
MC No MCAdults with SOT ≥ 18 YOA
2-dose Adults ≥ 50 YOAn n
CO-13
RSVPreF3 + AS01E Induces Robust CD4+ T -cell Responses in
Kidney and Lung Transplant Recipients
MedianQ3
Q1
MinimumMaximumKey
n 23 24 22 23 28 27 28 26 31 28 24 28
Increased CD4+ T -cell
responses were
consistent across
immunocompromised
groups (1- dose, 2- dose)
and adults ≥ 50 YOA
1.010.0100.01000.010000.0
Frequency of
RSVPreF3 -specific
CD4+ T -cells*
(per million of
CD4+ T -cells)
V1 V2 V3 V4
Adults with SOT ≥ 18 YOA
1-dose groupAdults with SOT ≥ 18 YOA
2-dose groupV1 V3 V4 V1 V2 V4 V2 V3
Adults ≥ 50 YOA
*Expressing ≥ 2 activation markers including ≥1 cytokine among CD40L, 4- 1BB, IL -2, TNF -α, IFN-γ, IL-13, and IL -17
Adults with SOT 1 -dose group: adults with kidney and lung transplant ≥ 18 YOA receiving 1 dose of RSVPreF3 + AS01E at Visit 1 (Day 1); adults with SOT 2 -dose group: adults with kidney and lung
transplant ≥ 18 YOA receiving 2 doses of RSVPreF3 + AS01E at Visit 1 (Day 1) and Visit 3 (30– 60 days post -Dose 1); Adults ≥50 YOA group: adults ≥ 50 YOA receiving 1 dose of RSVPreF3 + A S01E at
Visit 1 (Day 1); CD, cluster of differentiation; IFN, Interferon; IL, interleukin; SOT, solid organ transplant; TNF, tumor necrosis factor; V, Visit; YOA, years of ageRSV-OA=ADJ -023
CO-14
Safety
Preliminary results
CO-15
Solicited AEs Broadly Similar Between SOT Groups and ≥ 50 YOA
Group (Within 7 Days Post- Vaccination)
Grade 3 AEs were defined as administration -site erythema or swelling with a diameter >100 mm, fever with a temperature >39.0° C/102.2° F, and administration -site pain, headache, fatigue, myalgia, and
arthralgia that prevented normal activity. Adults with SOT 1 -dose group: adults with kidney and lung transplant ≥18 YOA receiving 1 dose of RSVPreF3 + AS01E at Visit 1 (Day 1); Adults with SOT 2 -
dose group: adults with kidney and lung transplant ≥18 YOA receiving 2 doses of RSVPreF3 + AS01E at Visit 1 (Day 1) and Visit 3 (30– 60 days post -Dose 1); Adults ≥50 YOA group: adults ≥50 YOA
receiving 1 dose of RSVPreF3 + AS01E at Visit 1 (Day 1); AE, adverse event; CI, confidence interval; SOT, solid organ transplant; YOA, years of age0102030405060708090100
Local SystemicErythema Arthralgia Fatigue Fever ≥38° C Headache Myalgia Swelling Pain8.5
(5.4, 12.6)8.5
(4.1, 15.0) 8.8
(4.5, 15.2)72.2
(66.3, 77.6) 68.6
(59.5, 76.9)76.0
(67.5, 83.2)
7.3
(4.5, 11.2)5.1
(1.9, 10.7)13.1
(9.3, 17.9)16.1
(10.0, 24.0)33.2
(27.5, 39.3)39.8
(30.9, 49.3)
1.2
(0.2, 3.3)1.7
(0.2, 6.0)24.7
(19.6, 30.4)25.4
(17.9, 34.3)29.0
(23.5, 34.9)32.2
(23.9, 41.4)
2.4
(0.5, 6.9)12.0
(6.9, 19.0)38.4
(29.8, 47.5)
0.8
(0.0, 4.4)35.2
(26.9, 44.2)39.2
(30.6, 48.3)Post-Dose 1
(Pooled SOT 1-dose and 2-dose groups; N=259)
Post-Dose 2 (SOT 2-dose group; N=118)
Adults ≥ 50 YOA (N=125)
Incidence of solicited Grade 3 AEs were low across groups (≤ 3% for any AE in any group)Participants
% (95% CI)RSV-OA=ADJ -023
CO-16
020406080100Related Unsolicited AEs Similar Between Groups
(Within 30 Days Post -Vaccination)
Most events in SOT groups
reflect background
morbidity (e.g. range of
infections, gastrointestinal and general AEs)
No pattern or clustering of events types to suggest a
safety concern
Adults with SOT 1 -dose group: adults with kidney and lung transplant ≥18 YOA receiving 1 dose of RSVPreF3 + AS01E at Visit 1 (Day 1); Adults with SOT 2 -dose group: adults with kidney and lung
transplant ≥18 YOA receiving 2 doses of RSVPreF3 + AS01E at Visit 1 (Day 1) and Visit 3 (30– 60 days post -Dose 1); Adults ≥50 YOA group: adults ≥50 YOA receiving 1 dose of RSVPreF3 + AS 01E at
Visit 1 (Day 1); AE, adverse event; CI, confidence interval; SOT, solid organ transplant; YOA, years of ageParticipants
% (95% CI)
Unsolicited AEs Related unsolicited AEsRSV-OA=ADJ -023
6.1
(3.5, 9.8)4.0
(1.3, 9.1)6.6
(2.9, 12.6)20.7
(15.9, 26.1)20.8
(14.1, 29.0)30.6
(22.5, 39.6)Post-Dose 1
(Pooled SOT 1-dose and 2-dose groups; N=261)
Post-Dose 2
(SOT 2-dose group; N=121)
Adults ≥ 50 YOA (N=125)
Grade 3
CO-17
SAEs Similar Between Dose 1 and Dose 2 SOT Groups
(Up to Safety Data Lock Point)
Adults with SOT 1 -dose group: adults with kidney and lung transplant ≥18 YOA receiving 1 dose of RSVPreF3 + AS01E at Visit 1 (Day 1); Adults with SOT 2 -dose group: adults with kidney and lung
transplant ≥ 18 YOA receiving 2 doses of RSVPreF3 + AS01E at Visit 1 (Day 1) and Visit 3 (30– 60 days post -Dose 1); Adults ≥50 YOA group: adults ≥50 YOA receiving 1 dose of RSVPreF3 + AS 01E at
Visit 1 (Day 1); CI, confidence interval; GBS, Guillain -Barré syndrome; pIMD , potential immune -mediated disease; SAE, serious adverse event; SOT, solid organ transplant; YOA, years of ageParticipants
% (95% CI)
020406080100
3.8
(1.3, 8.7)2.4
(0.5, 6.9)10.7
(5.8, 17.7)9.2
(4.8, 15.5)
Post -Dose 1
SOT 1-dose group Post -Dose 1
SOT 2-dose group Post -Dose 2
SOT 2-dose group Post -Dose 1
Adults ≥50 YOA
N 131 130 121 125
Median
follow -up170 days 30-60 days 136 days 171 daysNo specific pattern or clustering of SAEs
No cases of GBS or atrial fibrillationRSV-OA=ADJ -023
CO-18
AReSVi -006 Pivotal Efficacy Study:
Preliminary Updates from Season 3
Phase 3, Randomized, Placebo- Controlled, Multi -Country Study to Demonstrate Efficacy &
Safety of Single & Annual Revaccination Doses in Adults 60 Years & Older
NCT04886596
CO-19
RSV annual (N=4,968)
RSV 1 dose (N=4,988)
Placebo (N=10,031)RSV Season 1AReSVi -006 Phase 3 Trial Design1-4
Randomization (1:1)Re-randomization (1:1)RSV Season 2 RSV Season 3
RSVPreF3 + AS01E
(N=12,468)
Placebo
(N=12,498)D1RSVPreF3 + AS01E
Placebo
Older adults
≥ 60 YOANH: 1st Oct 2021 to 30 Apr 2022
SH: 1st Mar 2022 to 30 Sep 2022NH: 1st Oct 2022 to 31 Mar 2023
SH: 1st Mar 2023 to 30 Sep 2023
Primary endpoint: To demonstrate efficacy of RSVPreF3 + AS01E in prevention of RSV LRTD** in adults ≥ 60 YOA during first season2
Confirmatory secondary endpoints: To demonstrate efficacy of RSVPreF3 + AS01E in the prevention of RSV LRTD ** in adults ≥ 60 YOA over three seasons,
following a single dose and annual revaccination of RSVPreF3 + AS01E, and for each RSV subgroup (A and B) separately2
All RSV -LRTD** cases adjudicated by independent external adjudication committeeNH: 1st Oct 2023 to 30 Apr 2024
SH: 1st Mar 2024 to 30 Apr2024
RSV annual 1+1(N=3,582)
4,*
Figure adapted from Ison MG et al. Clin Infect Dis 2024. under the terms of the CC BY 4.0 Attribution License (https://creativecommons.org/licenses/by/4.0/ ); *Some participants in NH who came at
their Pre -season 3 visit before the approval of protocol amendment 5 received Dose 3; **LRTD defined as ≥2 lower respiratory symptoms/signs for ≥24 hours including ≥1 lower respiratory sign OR
≥3 lower respiratory symptoms for ≥24 hours. All cases of RSV were RT -PCR confirmed; D, day; LRTD, lower respiratory tract disea se; N, number of participants in the modified exposed set (S1),
dose 2- modified exposed set (S2), participants in the dose 2 -modified exposed set who did not receive dose 3 (RSV annual group);
NH, Northern Hemisphere; RT -PCR, reverse transcription -polymerase chain reaction; S, season; SH, Southern Hemisphere; YOA, years of age;
1. ClinicalTrials.gov, 2024. NCT04886596.; 2. Papi A et al. N Engl J Med 2023;388:595– 608; 3. Ison MG et al. Clin Infect Dis 2024;78:1732– 1744; 4. Unpublished dataEnd of
Study
Analysis
Study start
NH: 25 May 20212AReSVi- 006
RR
CO-20
~25,000 Participants Randomized in 17 Countries
Northern Hemisphere
(N=23,018
incl. ~9,000 in NA)
Southern Hemisphere
(N=1,948)
Austria
BelgiumEstoniaFinlandGermanyItalyPolandRussiaSpainUK
JapanSouth Korea
CanadaUnited StatesMexico
AustraliaNew Zealand
South Africa
RSVPreF3 Vaccine for Respiratory Syncytial Virus (RSV) in Older Adults. Presented at VRBPAC Meeting, March 1, 2023; FDA.gov (URL accessed August 2024);
NA, North America; UK, United Kingdom; VRBPAC, Vaccines and Related Biological Products Advisory CommitteeAReSVi- 006
CO-21
AReSVi -006 Case Definitions1,2
Signs and symptoms in addition to ≥ 1 RSV -positive swab detected by qRT-PCR
ARI
≥ 2 respiratory symptoms or signsOR
≥ 1 respiratory and 1 systemic symptom or sign for at least 24 hours Respiratory symptoms or signs
Fever/feverishness
Fatigue
Body aches
Headache
Decreased appetiteUpper respiratory symptoms
or signsLower respiratory
symptomsLower respiratory signsSystemic symptoms or signs
Sputum
Cough
DyspneaWheezing
Crackles/rhonchi
Tachypnea
Hypoxemia
O2 supplementNasal congestion
Sore throat
LRTD*≥ 2 lower respiratory symptoms or signs (≥ 1 sign) OR
≥ 3 lower respiratory symptoms for at least 24 hours Sputum
Cough
DyspneaLower respiratory
symptomsLower respiratory signs
Wheezing
Crackles/rhonchi
Tachypnea
Hypoxemia
O
2 supplement
Severe LRTD*≥ 2 lower respiratory signsOR
episode preventing normal,everyday activitiesLower respiratory signs
Wheezing
Crackles/rhonchi
Tachypnea
Hypoxemia
O
2 supplement
*USPI case definitions ; ARI, acute respiratory infection; LRTD, lower respiratory tract disease; qRT-PCR, quantitative reverse transcription -polymerase chain reaction;
1. GSK’s RSVPreF3 OA Vaccine (AREXVY). Presented at ACIP, 21 June 2023 https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2023- 06-21-23/03- RSV- Adults -Friedland -508.pdf (URL
accessed August 2024); 2. Papi A et al. N Engl J Med 2023;388:595– 608AReSVi- 006
CO-22
Single Dose of RSVPreF3 + AS01E Demonstrates Clinically
Meaningful Vaccine Efficacy Against RSV -LRTD* Over 3 RSV
Seasons1-4
*VE is maintained up to end of Season 3 NH. Confirmatory secondary endpoint is demonstrated with LL >20%; **96.95% CI; ***97.5% CI; ****95% CI; *****VE was estimated using a Poisson model
adjusted for age, region, and season (“with season as a covariate”) or for age and region (“without season as a covariate”; p ost-hoc analyses). For Season only VE, season could not be considered a
covariate, so data are presented in the “without season as a covariate” column; CI, confidence interval; LRTD, lower respirat ory tract disease; m, month; n/a, not applicable; NH, Northern Hemisphere;
S, Season; SH, Southern Hemisphere; VE, vaccine efficacy .
1. Papi A et al. N Engl J Med 2023;388:595– 608; 2. Ison MG et al. Clin Infect Dis 2024;78:1732– 1744; 3. Gerber S. AREXVY (Adjuvanted RS VPreF3) 2 -Year Update. Presented at ACIP 26 June 2024.
https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2024- 06-26-28/03- RSV- Adult- Gerber -508.pdf (accessed August 2024); 4. Unpublished dataSeason
(median follow -up time)RSVPreF3 +
AS01E Placebo% VE (CI)*****
W/ season
covariateW/o season
covariate Number of events (n/N)
Season 1** (end of NH S1; 6.7m)
1 7 / 12,466 40 / 12,494 n/a 82.6 (57.9, 94.1)
Season 1 + 2*** (end of NH S2; 17.8m)
2 30 / 12,469 139 / 12,498 67.2 (48.2, 80.0) 74.5 (60.0, 84.5)
2 calendar years****
(end of SH S2; 23.3m)3 32 / 12,468 154 / 12,498 67.7 (52.3, 78.7) 73.3 (60.7, 82.4)
Season 1 –3***
(end of NH S3; 30.6m)4 48 / 12, 468 215 / 12,498 62.9 (46.7, 74.8) 69.1 (55.8, 78.9)
0% 20% 40% 60% 80% 100%AReSVi- 006
Vaccine Efficacy (CI) *****
CO-23
Vaccine Efficacy of Single Dose of RSVPreF3 + AS01E Against
Severe RSV -LRTD Over 3 RSV Seasons1-4
Season
(median follow -up time)RSVPreF3 +
AS01E Placebo% VE (95% CI) *
W/ season
covariateW/o season
covariate Number of events (n/N)
Season 1 (end of NH S1; 6.7m)
1 1 / 12,466 17 / 12,494 n/a 94.1 (62.4, 99.9)
Season 1 + 2 (end of NH S2; 17.8.m)
2 7 / 12,469 48 / 12,498 78.8 (52.6, 92.0) 82.7 (61.6, 93.4)
2 calendar years (end of SH S2; 23.3m)
3 9 / 12,468 54 / 12,498 74.9 (48.4, 89.2) 78.6 (56.3, 90.7)
Season 1 –3
(end of NH S3; 30.6m)4 15 / 12,468 75 / 12,498 67.4 (42.4, 82.7) 72.3 (51.3, 85.2)
0% 20% 40% 60% 80% 100%
*VE estimated using Poisson model adjusted for age, region, and season (“with season as a covariate”) or for age and region (“ without season as a covariate”; post hoc analyses). For Season only
VE, season could not be considered a covariate, so data are presented in the “without season as a covariate” column ; CI, confidence interval; LRTD, lower respiratory tract disease; m, month; n/a, not
applicable; NH, Northern Hemisphere; S, Season; SH, Southern Hemisphere; VE, vaccine efficacy; 1. Papi A et al. N Engl J Med 2023; 2. Ison MG et al. Clin Infect Dis 2024; 3. Gerber S. AREXVY
(Adjuvanted RSVPreF3) 2 -Year Update. Presented at ACIP 26 June 2024. https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2024- 06-26-28/03- RSV- Adult- Gerber -508.pdf (accessed August
2024); 4. Unpublished dataAReSVi- 006
Vaccine Efficacy (95% CI)
CO-24
Single Dose of RSVPreF3 + AS01E Shows Consistent
Vaccine Efficacy for Subgroups Over 3 RSV Seasons
*COPD, asthma, any chronic respiratory/pulmonary disease, diabetes type 1 or type 2, chronic heart failure, advanced liver or renal disease; **97.5% CI for confirmatory secondary endpoint; 95% CI for
other endpoints; ***Vaccine efficacy was estimated using a Poisson model adjusted for age, region, and season (“with season a s a covariate”);
COPD, chronic obstructive pulmonary disease; CI, confidence interval; LL, lower limit; LRTD, lower respiratory tract disease; VE, vaccine efficacy; YOA, years of age. Unpublished dataAReSVi- 006
RSVPreF3 +
AS01E Placebo
Number of events (n/N)
LRTD 48 / 12,468 215 / 12,498
RSV-A 14 / 12,468 80 / 12,498
RSV-B 34 / 12,468 135 / 12,498
Severe LRTD 15 / 12,468 75 / 12,498
60–69 YOA 28 / 6962 117 / 6981
70–79 YOA 15 / 4489 85 / 4489
≥1 pre -existing comorbidity of interest*25 / 5014 116 / 4951
≥1 cardiorespiratory condition of interest 17 / 2577 85 / 2504
≥1 endocrine metabolic condition of interest 12 / 3243 55 / 3274
Pre-frail 12 / 4794 67 / 4779
0% 20% 40% 60% 80% 100%
Vaccine Efficacy (CI)**,***
Confirmatory
secondary
endpoints
VE cannot be
reliably estimated
for adults
≥ 80 YOA and frail
group as too few
cases were
observed
VE with season covariateMedian Follow -up: 30.6 Months
62.9% (46.7, 74.8)
69.8% (42.2, 85.7)
58.6% (35.9, 74.1)
67.4% (42.4, 82.7)
60.3% (39.5, 74.8)
70.6% (48.4, 84.3)
64.7% (45.1, 78.1)
68.1% (45.7, 82.3)
63.9% (31.4, 82.5)
70.1% (43.9, 85.3)LL of the 2- sided CI for
vaccine efficacy was > 20%
CO-25
Vaccine Efficacy of Single Dose of RSVPreF3 + AS01E
Against RSV- LRTD by RSV Season1-4
*96.95% CI for the primary endpoint (S1 RSV -LRTD, overall); 95% CI for other endpoints; CI, confidence interval; LRTD, lower resp iratory tract disease; m, month; n/a, not applicable; NH, Northern
Hemisphere; S, Season; SH, Southern Hemisphere; VE, vaccine efficacy
1. Papi A et al. N Engl J Med 2023;388:595– 608; 2. Ison MG et al. Clin Infect Dis 2024;78:1732– 1744; 3. GSK. Data on File; 2024N557587_00; 4. Unpublished dataSeason
(median follow -up time)RSVPreF3 +
AS01E Placebo
% VE (CI)* Number of events (n/N)
Season 1 (end of NH S1; 6.7m)
1 7 / 12,466 40 / 12,494 82.6 (57.9, 94.1)
Season 2 only (end of NH S2; 6.3m)
2 20 / 4991 91 / 10,031 56.1 (28.2, 74.4)
Season 2 only (end of SH S2; 11.9m)
3 22 / 4988 106 / 10,031 58.5 (33.9, 75.0)
Season 3 only (end of NH S3; 7m)
4 16 / 4988 61 / 10,031 48.0 (8.7, 72.0)Vaccine Efficacy (CI)*
0% 20% 40% 60% 80% 100%AReSVi- 006
CO-26
Vaccine Efficacy of Single Dose of RSVPreF3 + AS01E Against
RSV-LRTD in Adults with ≥ 1 Comorbidity of Interest* by RSV Season1-4
*Conditions of interest included any chronic respiratory/pulmonary disease (including chronic obstructive pulmonary disease an d asthma) and chronic heart failure (cardiorespiratory), and diabetes
mellitus type 1 or type 2 and advanced liver or renal disease (endocrine or metabolic); CI, confidence interval; COPD, chroni c obstructive pulmonary disease; LRTD, lower respiratory tract disease;
m, month; NH, Northern Hemisphere; S, Season; SH, Southern Hemisphere; VE, vaccine efficacy; YOA, years of age
1. Papi A et al. N Engl J Med 2023;388:595– 608; 2. Ison MG et al. Clin Infect Dis 2024;78:1732– 1744; 3. GSK. Data on File; 2024N557587_00; 4. Unpublished dataSeason
(median follow -up time)RSVPreF3 +
AS01E Placebo
% VE (95% CI) Number of events (n/N)
Season 1 (end of NH S1; 6.7m)
1 1 / 4937 18 / 4861 94.6 (65.9, 99.9)
Season 2 only (end of NH S2; 6.3m)
2 12 / 1981 48 / 3895 51.5 (7.4, 76.6)
Season 2 only
(end of SH S2; 11.9m)3 13 / 1990 55 / 3916 54.2 (15.1, 77.1)
Season 3 only
(end of NH S3; 7m)4 8 / 2000 37 / 3924 57.8 (8.0, 83.0)Vaccine Efficacy (95% CI)
0% 20% 40% 60% 80% 100%AReSVi- 006
CO-27
~ 25,000 participants in pivotal efficacy trial
Cumulative follow -up occurred across all groups for median of
31.7 months
Safety profile of vaccine in adults ≥ 60 YOA remains acceptable
and consistent with label1
Frequency of SAEs/ pIMDs remained low and similar across groups
No reports of GBS, ADEMSafety Profile Remains Consistent and Acceptable Over
3 Seasons
ADEM, acute disseminated encephalomyelitis; GBS, Guillain -Barré syndrome; pIMD , potential immune -mediated disease; SAE, serious adverse event;
YOA, years of age; 1. FDA, 2024. AREXVY Prescribing Information (PI); https://www.fda.gov/media/167805/download (URL accessed Aug 2024)AReSVi- 006
CO-28
Public Health Benefits with RSVPreF3 + AS01E Vaccination Over 3 Years
71,85595,759
020,00040,00060,00080,000100,000120,000
RSV-LRTD Cases Averted493657
0100200300400500600700
RSV-related Deaths Averted+23,904 averted +164 averted
7,0099,340
01,0002,0003,0004,0005,0006,0007,0008,0009,00010,000
RSV-related Hospitalizations
Averted+2,331 averted
Potential RSV outcomes averted with vaccination vs no vaccination over 3 years based on 30.6- month follow up from
Study 006 and over 2 years based on 23.3- month follow -up from Study 006 among US adults aged 50- 59 years with COPD
Estimated
Outcomes
Averted
Assuming same vaccination coverage as influenza vaccines from 2022- 2023 season (https://www.cdc.gov/flu/fluvaxview/interactive -general -population.htm); Analysis includes 3,299,241 US adults
with COPD aged 50 -59 years, with 1,652,920 (50.1%) receiving RSVPreF3 + AS01E; Estimated health outcomes over 2 years based on vaccine efficacy estimates using 23.3- month follow -up data from
RSV OA=ADJ -006 Phase 3 Trial; Estimated health outcomes over 3 years based on vaccine efficacy estimates using 30.6- month follow -up data from RSV OA=ADJ -006 Phase 3 Trial
CO-29
Overview of Clinical Development Program
CO-30
Overview of Clinical DevelopmentCo-administration
Safety, reactogenicity, and Immunogenicity
RSV OA=ADJ -011 study
(Extension of Study 002)
Adults ≥ 60 YOA
Persistence and safety and immunogenicity of
a re-vaccination doseRSV OA=ADJ -002 study
Adults 18– 40 or 60– 80 YOA
First-in-human safety, immunogenicity,
formulation, and dosing selectionAReSVi -006 study
Adults ≥ 60 YOA
Pivotal efficacy study
AReSVi -004 study
Adults ≥ 60 YOA
Safety, reactogenicity, immunogenicity,
persistence, and re- vaccination
RSV OA=ADJ -023 study
Immunocompromised adults ≥ 18 YOA
(lung and kidney transplant recipients)
Safety and immunogenicity
Phase 1/2 Phase 2b Phase 3
CompletedOngoing/in progress/
data not yet public
RSV OA=ADJ -017 study
Adults ≥ 65 YOA
Co-administration with FLU -aQIV
RSV OA=ADJ -007 study
Adults ≥ 60 YOA
Co-administration with FLU -QIV
RSV OA=ADJ -008 study
Adults ≥ 65 YOA
Co-administration with FLU -QIV-HD
RSV OA=ADJ -018 study
Adults 50−59 YOA (incl. adults at
increased risk of RSV -LRTD) vs ≥ 60 YOA
Safety, reactogenicity, immunogenicity
RSV OA=ADJ -025 study
Adults 18– 49 YOA at increased risk
vs adults ≥ 60 YOA
Immunogenicity and safety
RSV OA=ADJ -012 study
(Extension of Study 006)
Extension & crossover study
in adults ≥ 60 YOA
Immunogenicity and safety of different
re-vaccination schedules and persistence of
single dose
RSV OA=ADJ -020 study
Adults ≥ 50 YOA
Co-administration with HZ/ su vaccine
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;
M: month; PCV20, 20 -valent pneumococcal conjugate vaccine; RSV -LRTD: respiratory syncytial virus lower respiratory tract disease; YOA: years of age
All studies ClinicalTrials.gov; All URLs accessed October 2024
RSV OA=ADJ -019 study
Adults ≥ 60 YOA
Co-administration with PCV20
RSV OA=ADJ -013 study
Adults ≥ 50 YOA
Co-administration with
COVID -19 mRNA vaccine
CO-31
Summary
CO-32
Conclusions
For solid organ transplant recipients on mycophenolate, a second dose of RSVPreF3 + AS01E
resulted in RSV -A and RSV -B neutralizing antibody responses close to levels observed in adults
≥ 50 YOA at same time pointOne dose of RSVPreF3 + AS01E provides robust RSV -A and RSV -B neutralizing antibody
responses and high CD4+ T -cell responses; acceptable safety profile in kidney and lung
transplant recipients ≥ 18 YOA
1
Ahead of this year’s RSV season, it is important to protect vulnerable individuals ≥ 50 YOA who
are at high-risk for severe RSV disease RSVPreF3 + AS01E provides clinically meaningful efficacy over 3 seasons
(median follow up time 30.6 months) in ≥ 60 YOA, with a continued acceptable safety profile
Estimated public health benefits of RSVPreF3 + AS01E are increased given its efficacy
over 3 seasons as compared to previous efficacy estimates
2
3
4
5
CO-33
Meeting of the Advisory Committee on
Immunization Practices (ACIP)
Centers for Disease Control and Prevention
October 24, 2024
Susan Gerber, MD
Medical Director
GSK
Presentation by GSK at ACIP October 24, 2024