Document text
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AREXVY (Adjuvanted RSVPreF3)
2-Year Update
ACIP June 26, 2024
Susan Gerber, MD
Medical Director
GSK
Presentation by GSK at ACIP June 26, 2024
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AREXVY Indications
AREXVY now 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 June 2024)
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Risk Factors for Severe RSV Disease Are Highly Prevalent Among
Adults ≥ 50 Years with Disparities Observed by Race and Ethnicity
▪31.4% of adults 50–59 YOA and 46.9% of adults ≥ 60 YOA are diagnosed with ≥ 1 risk factor for severe RSV diseasea
▪Mexican American/other Hispanic and NH Black adults have significantly higher prevalence of ≥ 1 diagnosed risk factor in
each of these age groups (vs. NH White adults)b
aSelf-reported diagnosis of the following conditions: CHF, CHD, stroke, angina pectoris, MI, COPD (COPD, emphysema, or current chro nic bronchitis), asthma (current), diabetes, liver disease (current), renal
disease. bOther race/multi -racial results not presented.
*Statistically significant based on two -sided P < 0.05. P -values were calculated based on pairwise chi -square analysis on 2x2 ta bles using non -Hispanic White adults as the reference group.
Notes: Retrospective, cross -sectional analysis of pooled NHANES data spanning the period 2011 -March 2020 .Weighting to the United States population conducted in accordance with NHANES published
guidelines: https://wwwn.cdc.gov/nchs/nhanes/tutorials/weighting.aspx . CHD, coronary heart disease; CHF, congestive heart failure; COPD, chronic obstructive pulmonary disease; MI, myocardial infar ction;
NH, Non -Hispanic; NHANES, National Health and Nutrition Examination Survey; YOA, years of age.Horn et al. NFID ACVR, May 8 -10, 2024 31.4%46.9%
29.9%44.9% 43.6%
34.1%*36.9%*
24.1%*50.4%*54.0%*
29.9%44.9%
34.1%*50.4%*
36.9%*54.0%*
24.1%*43.6%
0%20%40%60%
50-59 years ≥60 yearsPercentage of US adults with
≥1 diagnosed risk factor for
severe RSV disease
NH White Mexican American/other Hispanic NH Black NH Asian50–5 9 YOA ≥ 60 YOA% of
US adults with
≥ 1 diagnosed risk
factor for severe
RSV disease
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AReSVi -004: Immunogenicity, Safety, Reactogenicity and
Persistence of Single Dose of AREXVY Vaccine and
Different Revaccination Schedules in Adults ≥ 60 YOA
Randomized, open -label, multi -country study (NCT04732871)
Presentation by GSK at ACIP June 26, 2024
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AReSVi-004 Phase 3 Study Design1-3
Timepoint
HI only
(n≈215)D1 M13 M24 M25 M60
Presentation by GSK at ACIP June 26, 2024*RSV M24 revaccination: Participants receiving first dose (Dose 1) of AREXVY at Day 1 followed by revaccination dose at 24 months post Dose 1; **Primary endpoints: NAb
(neutralizing antibody) geometric mean titers (RSV-A and RSV-B) at Day 1 (pre-vaccination), D31, M6, and M12 post-dose 1; ***CMI response in terms of frequency of RSVPreF3-
specific CD4+ and/or CD8+ T-cells expressing > 2 activation markers; CMI, cell-mediated immunity; HI, humoral immunity; 1. Schwarz TF et al. 2023; 2. ClinicalTrials.gov.
NCT04732871; 3. GSK, 2024 https://www.gsk-studyregister.com/en/trial-details/?id=212496 (All URLs accessed June 2024)M12 M18 M30 M36 M37 M42 M48 M49 M54
HI + CMI
(n≈115)
HI + CMI
(n≈345)Safety
(n≈645)
RSV 1 Dose
N≈330
RSV Annual
N≈9901st analysis 2nd analysis 3rd analysisAnalyses may be performed or
regrouped depending on data availabilityFinal End
of Study
analysis AREXVY
Blood sample for HI responses
Blood sample for CMI responses4th analysis
R
3:1:1Current analysis
Re-randomization 1:1 (N≈ 330)
HI only
(n≈215)HI + CMI
(n≈115)
RSV M24
Revaccination*
N≈330
All participants followed for safety
Primary objective: To evaluate humoral immune response following 1-dose primary schedule up to 12 months post-dose 1**
Key secondary objectives: To evaluate humoral and CMI *** responses following 1-dose primary schedule and re-vaccination doses, up to study end (M60);
safety and reactogenicity also assessedAReSVi -004
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Presentation by GSK at ACIP June 26, 2024AReSVi -004
GMT
(ED60)
[95%CI]
M
6M
12M
18M
24M
25M
13100010000
M
6M
12M
18M
24M
25M
13RSV Annual Revaccination RSV M24 Revaccination RSV 1 Dose
TimepointD
31D
1100010000
D
31D
1RSV-A Serum Neutralization Titers RSV-B Serum Neutralization TitersHigher RSV -A and RSV -B Neutralizing Antibody Titers
Observed After 24 Month Vaccination Interval
RSV Annual revaccination (N=250 -341): Participants receiving first dose (Dose 1) of AREXVY at Day 1, followed by revaccination d ose at 12 months post Dose 1 and at 24 months post Dose 1;
RSV M24 revaccination (N= 223 -319): Participants receiving first dose (Dose 1) of AREXVY at Day 1 followed by revaccination dose at 24 months post Dose 1;
RSV 1 dose (N=281 -318): Participants receiving single dose (Dose 1) of AREXVY at Day 1; ED60: estimated dilution 60; GMT: geomet ric mean titer
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CD4+ T -Cell Responses Increased 1 -Month Post Each
Vaccination DoseAReSVi -004
Presentation by GSK at ACIP June 26, 2024RSVPreF3 CD4+
T-cells, /106 cells
0500100015002000
1 201 401 601 M
6M
12M
18M
24M
25M
13D
31D
1
TimepointRSV Annual Revaccination RSV M24 Revaccination RSV 1 Dose
RSV Annual revaccination (N=216 -286): Participants receiving first dose (Dose 1) of AREXVY at Day 1, followed by revaccination dose at 12 months post Dose 1 and at 24 months post Dose 1; RSV
M24 revaccination (N=68 -94): Participants receiving first dose (Dose 1) of AREXVY at Day 1 followed by revaccination dose at 24 months post Dose 1; RSV 1 dose (N=83 -95):
Participants receiving single dose (Dose 1) of AREXVY at Day 1; CD4+ T -cells expressing ≥ 2 activation markers including ≥ 1 cytokine among CD40L, 4 -1BB, IL -2, TNF -α, IFN -γ, IL-13, IL -17
events/ 106 cells; (by intracellular staining)
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Lower Prevaccination RSV-A NAb Titers Associated with Higher
Seroresponse Rates (≥ 4 -Fold Increase) Following Revaccination
n/N 22 / 67 4 / 67 6 / 67 3 / 67
NAb baseline
GMT (ED60)193 – <1,304 1,304 – <2,381 2,381 – <4,078 4,078 – 123,535Participants with
≥ 4-fold increase
in RSV- A NAb
titers at
M13 vs M12
[95% CI]
29 / 55 23 / 56 10 / 56 7 / 56
283 – <1,000 1,000 – <1,849 1,849 – <3,736 3,736 – 38,8400%20%40%60%80%100%
0 1 2 3 432.8
(21.8, 45.4)
6.0
(1.7, 14.6)9.0
(3.4, 18.5) 4.5
(0.9, 12.5)RSV Annual Revaccination
1 2 3 4Participants with
≥ 4-fold increase
in RSV- A NAb
titers at
M25 vs M24
[95% CI]
0%20%40%60%80%100%
0 1 2 3 41 2 3 417.9
(8.9, 30.4) 12.5
(5.2, 24.1)41.1
(28.1, 55.0)52.7
(38.8, 66.3)
Quartile* Quartile*RSV M24 Revaccination
Presentation by GSK at ACIP June 26, 2024*Participants were grouped into quartiles depending on their baseline NAb titers: 1 = baseline NAb min–<1; 2 = baseline NAb 1–<2 (median); 3 = baseline NAb 2 (median) –<3;
4 = baseline NAb 3–4. Participants in the quartile 1 had the lowest pre -revaccination NAb and those in the quartile 4 had the highest; ED60, serum dilution inducing 60% inhibition in plaque -
forming units; GMT, geometric mean titer; NAb, neutralizing antibody; RSV Annual revaccination: Participants receiving the first dose (Dose 1) of Arexvy at Day 1, followed by a
revaccination dose at 12 months post Dose 1 and at 24 months post Dose 1; RSV M24 revaccination: Participants receiving the f irst dose (Dose 1) of Arexvy at Day 1 followed by a
revaccination dose at 24 months post Dose 1.AReSVi -004
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Lower Prevaccination RSV-B NAb Titers Associated with Higher
Seroresponse Rates (≥ 4 -Fold Increase) Following Revaccination
Presentation by GSK at ACIP June 26, 2024*Participants were grouped into quartiles depending on their baseline NAb titers: 1 = baseline NAb min–<1; 2 = baseline NAb 1–<2 (median); 3 = baseline NAb 2 (median) –<3;
4 = baseline NAb 3–4. Participants in the quartile 1 had the lowest pre -revaccination NAb and those in the quartile 4 had the highest; ED60, serum dilution inducing 60% inhibition in plaque -
forming units; GMT, geometric mean titer; NAb, neutralizing antibody; RSV Annual revaccination: Participants receiving the first dose (Dose 1) of Arexvy at Day 1, followed by a
revaccination dose at 12 months post Dose 1 and at 24 months post Dose 1; RSV M24 revaccination: Participants receiving the f irst dose (Dose 1) of Arexvy at Day 1 followed by a
revaccination dose at 24 months post Dose 1.0%20%40%60%80%100%
0 1 2 3 41 2 3 40%20%40%60%80%100%
0 1 2 3 41 2 3 4
Quartile* Quartile*58.2
(44.1, 71.3)
37.5
(24.9, 51.5)
19.6
(10.2, 32.4)12.5
(5.2, 24.1)17.9
(9.6, 29.2)
7.5
(2.5, 16.6)4.5
(0.9, 12.5)3.0
(0.4, 10.4)RSV Annual Revaccination RSV M24 Revaccination
Participants with
≥ 4-fold increase
in RSV-B NAb
titers at
M13 vs M12
[95% CI]Participants with
≥ 4-fold increase
in RSV-B NAb
titers at
M25 vs M24
[95% CI]
n/N 12 / 67 5 / 67 3 / 67 2 / 67
NAb baseline
GMT (ED60)351 – <1,607 1,607 – <2,453 2,453 – <4,133 4,133 – 36,39132 / 55 21 / 56 11 / 56 7 / 56
271 – <1,190 1,190 – <2,122 2,122 – <3,845 3,845 – 26,385AReSVi -004
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Safety and Reactogenicity Profile in Individuals Revaccinated at
Month 24 Similar to First Dose
Solicited AEs reported within 4 days of each vaccine dose (exposed set)
AE, adverse event; M, month; RSV 24M revaccination: Participants receiving the first dose (Day 1 Dose) of RSVPreF3 OA investi gational vaccine at Day 1 followed by a revaccination
dose at 24 months (M24 Dose) post -Dose 1 (n=270 -328). Grade 3: >100 mm for erythema and swelling; significant pain at rest, prev ents normal everyday activities for pain; prevents
normal activity for headache, fatigue, myalgia, and arthralgia; >39.0 °C (102.2 °F) for fever.RSV M24 Revaccination
(Day 1 Dose)RSV M24 Revaccination
(M24 Dose)
020406080100
% of
Participants
M24 Revac
(Day 1)
M24 Revac
(M24)
M24 Revac
(Day 1)
M24 Revac
(M24)
M24 Revac
(Day 1)
M24 Revac
(M24)
M24 Revac
(Day 1)
M24 Revac
(M24)
M24 Revac
(Day 1)
M24 Revac
(M24)
M24 Revac
(Day 1)
M24 Revac
(M24)
M24 Revac
(Day 1)
M24 Revac
(M24)
M24 Revac
(Day 1)
M24 Revac
(M24)Grade 3
11.6 11.461.3
56.1
10.17.714.917.830.535.2
1.5 1.921.326.332.6 31.1Arthralgia Fatigue Fever Headache Myalgia Erythema Pain Swelling
Unsolicited AEs, SAEs, Fatal SAEs and pIMDs of individuals who were revaccinated at Month 24 are also similar to those vaccinated at Day 1Local SystemicAReSVi -004
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AReSVi -004 Summary
Revaccination at a 24 -month interval provides higher RSV -A and RSV -B neutralizing antibody
titers as compared to a 12 -month interval 1
Safety and reactogenicity profiles of second dose comparable with first dose 3
The l ower the prevaccination RSV-A and RSV -B neutralizing antibody titers observed at 2 years
post initial vaccination, the higher the seroresponse rates after revaccination 2
Presentation by GSK at ACIP June 26, 2024
Future results from this trial will help inform optimal revaccination timing 4
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Postmarketing Safety Update
Presentation by GSK at ACIP June 26, 2024
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AREXVY: Post -Licensure Safety Surveillance After 1 Year
Reflects Acceptable Safety Profile in Clinical Trials
Presentation by GSK at ACIP June 26, 2024*IQVIA NPA Rapid Weekly TRx, to 13 May 2024
**Based on GSK safety database, spontaneous AE reports not necessarily causally -related to vaccination
1. Sejvar JJ, et al. 2011; AE: adverse event ; VSD: vaccine safety datalink; BEST: biologics effectiveness and safety
▪1,640 AE reports received (launch 3 May ’23 -2 May ‘24)**
▪82% from US
▪89% non -serious
▪Since launch, GSK received 12 reports of GBS, all from US
▪Observed vs expected, based on 7,246,910 AREXVY doses administered
in US and background incidence rate = 2.1 / 100,000 PY3
Vaccine
Exposure▪~ 8 million doses of AREXVY administered in US since launch*
AE▪1,640 AEs (from US, 1,344 AE reports received) [launch 3 May ’23 -2 June ’24]**
▪89% non -serious
▪Majority related to labelled reactions
GBS▪Since launch, GSK received 13 reports of GBS, all from US
▪Reports do not exceed expected background incidence1
▪17 cases expected in absence of vaccination
▪VSD and BEST initiative will provide additional assessment of GBS
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Overview of Clinical Development Program
Presentation by GSK at ACIP June 26, 2024
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AREXVY Clinical Development Program
AReSVi -004 study
Older adults ≥60 YOA
Safety, reactogenicity, immunogenicity, persistence, and re -vaccination
RSV OA=ADJ -019 study
Older adults ≥60 YOA
Safety, reactogenicity, immunogenicity when
co-administered with PCV20
RSV OA=ADJ -020 study
Older adults ≥50 YOA
Safety, reactogenicity, immunogenicity when
co-administered with HZ/ su vaccine
Phase 2b
Phase 3
Completed
Ongoing/
in progress
RSV OA=ADJ -025 study
Adults 18 –49 years of age compared
to older adults ≥60 years of age
Safety and immunogenicity
RSV OA=ADJ -007,
RSV OA=ADJ -017, RSV OA=ADJ -008
Safety, reactogenicity, immunogenicity when
co-administered with FLU -QIV, FLU -aQIV ,
FLU-QIV-HD, respectively
RSV OA=ADJ -013 study
Older adults ≥50 YOA
Safety, reactogenicity, immunogenicity when
co-administered with COVID -19 mRNA
vaccine
Presentation by GSK at ACIP June 26, 2024FLU-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; 1MPD1: 1 month post dose 1; PCV20: 20 -valent pneumococcal conjugate vaccine; YOA: years of age
All studies ClinicalTrials.gov; All URLs accessed June 2024AReSVi -006 study
Older adults ≥60 YOA
Pivotal efficacy study
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 -023 study
Immunocompromised adults ≥18 YOA
(lung and renal transplant recipients)
Safety and immunogenicity
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AREXVY (Single dose)AREXVY Placebo% VE (95% CI)
W/ season
covariateW/o season
covariateNumber of events (n/N)
RSV-LRTD 32 / 12,468 154 / 12,498 67.7% (52.3, 78.7) 73.3% (60.7, 82.4)
≥ 1 comorbidity of interest* 17 / 5,000 79 / 4,942 67.1% (43.6, 81.8) 73.1% (54.2, 85.1)
≥ 70 years of age 12 / 5,506 74 / 5,517 74.6% (52.6, 87.5) 79.1% (61.3, 89.7)
Pre-frail** 9 / 4,794 50 / 4,779 71.3% (40.6, 87.7) 77.0% (52.7, 90.1)
Severe RSV-LRTD 9 / 12,468 54 / 12,498 74.9% (48.4, 89.2) 78.6% (56.3, 90.7)
Vaccine Efficacy0% 20% 40% 60% 80% 100%Efficacy of a Single Dose of AREXVY over 2 Calendar Years
Presentation by GSK at ACIP June 26, 2024
Median follow-up: 23.3 monthsAReSVi -006
*Comorbidities of interest: COPD, asthma, any chronic respiratory or pulmonary disease, heart failure (cardiorespiratory cond ition), diabetes mellitus type 1 or 2, advanced liver or renal
disease (endocrine or metabolic condition); **frailty assessed using gait speed test: walking speed < 0.4 m/s or not able to perform test (frail), walking speed 0.4 –0.99 m/s
(pre-frail), walking speed ≥1 m/s (fit); Due to too few cases observed, cannot conclude VE for frail and ≥ 80 years of age
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Conclusion
▪Immunogenicity data supports potential for revaccination with AREXVY
▪Stronger immune responses were observed in those revaccinated after
24-month interval compared to those revaccinated annually
▪Results from ongoing Phase 3 studies will help inform timing of
revaccination
▪AREXVY provides protection over 2 calendar years
▪Acceptable safety profile following administration of ~ 8 million doses
▪FDA recently expanded AREXVY’s indication to include use in individuals
50–59 YOA at increased risk for RSV-LRTD
▪Will help to close equity gap by broadening access for populations at
increased risk for severe disease caused by RSV
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AREXVY (Adjuvanted RSVPreF3)
2-Year Update
ACIP June 26, 2024
Susan Gerber, MD
Medical Director
Presentation by GSK at ACIP June 26, 2024