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MedicalSafety and Efficacy of
Bivalent RSV Prefusion F Vaccine
in Vaccinated Mothers and their Infants
Iona Munjal, MD
Senior Director, Vaccine Research and Development
178Worldwide Research, Development and Medical
Vaccine Research and DevelopmentBivalent RSV Prefusion F Vaccine
Proposed Indication:
Prevention of lower respiratory
tract disease and severe lower
respiratory tract disease caused by
respiratory syncytial virus (RSV)DOSE LEVEL•120 µg without an adjuvant
•Dose contains 60 µg dose of
each prefusion protein
antigen, in a 0.5 mL injection
PRESENTATION•Single dose 2 mL vial
•1 mL Pre-filled syringe
•Vial adaptor
STORAGE •Refrigeration at 2 °Cto 8°CInfants from birth through 6 months of age by active immunization of pregnant individuals
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Vaccine Research and DevelopmentGroundbreaking Structural Work by NIH Elucidated that RSV F on the
Virus Exists as an Unstable Prefusion Form
Only prefusion F can bind host
cells for RSV to infect
Antibodies specific to the
prefusion form are most effective
at blocking virus infection
McLellan et al. Science, Nov 2013
Postfusion F Trimer
fused membranePrefusion F Trimer
Antigenic Site Ø
(Nirsevimab, AM22)
Viral membraneAntigenic Site II
(Synagis)
Antigenic Site IV
(101- F, AM14)
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Vaccine Research and Development2018 2019 2020 2021 2022+
Phase 1/2
First -in-Human1Adults 18- 85y
Dose Ranging
+/-Al(OH)3 +/-Influenza
Phase 2b2Pregnant Women 18–49y
Safety and ImmunogenicityEarly Efficacy
Phase 2b
3 Nonpregnant Women 18– 49y
Concomitant Tdap
Phase 34 Adults 18- 49y
Lot Consistency Study
Phase 35 Pregnant Women ≤49y
Pivotal Efficacy
1. A Study to Describe the Safety and Immunogenicity of a RSV Vaccine in Healthy Adults. NCT03529773.
2. A Phase 2bPlacebo- Controlled, Randomized Study of an RSV Vaccine in Pregnant Women. NCT04032093.
3. A Study of an RSV Vaccine When Given Together with Tdap in Healthy Nonpregnant Women Aged Between 18 to 49 Years. NCT04071158.
4. Clinical Lot Consistency for RSVpreF in a Population of Healthy Adults 18 to ≤49 Years of Age. NCT05096208.
5. A Trial to Evaluate the Efficacy and Safety of RSVpreF in Infants Born to Women Vaccinated During Pregnancy. NCT04424316 .Pfizer’s RSVpreF Maternal Immunization Clinical Development Program
181Worldwide Research, Development and Medical
Vaccine Research and Development2018 2019 2020 2021 2022+
Phase 1/2
First -in-Human1Adults 18- 85y
Dose Ranging
+/-Al(OH)3 +/-Influenza
Phase 2b2Pregnant Women 18–49y
Safety and ImmunogenicityEarly Efficacy
Phase 2b
3 Nonpregnant Women 18- 49y
Concomitant Tdap
Phase 34 Adults 18- 49y
Lot Consistency Study
Phase 35 Pregnant Women ≤49y
Pivotal Efficacy
1. A Study to Describe the Safety and Immunogenicity of a RSV Vaccine in Healthy Adults. NCT03529773.
2. A Phase 2bPlacebo- Controlled, Randomized Study of an RSV Vaccine in Pregnant Women. NCT04032093.
3. A Study of an RSV Vaccine When Given Together with Tdap in Healthy Nonpregnant Women Aged Between 18 to 49 Years. NCT04071158.
4. Clinical Lot Consistency for RSVpreF in a Population of Healthy Adults 18 to ≤49 Years of Age. NCT05096208.
5. A Trial to Evaluate the Efficacy and Safety of RSVpreF in Infants Born to Women Vaccinated During Pregnancy. NCT04424316 .Pfizer’s RSVpreF Maternal Immunization Clinical Development Program
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Vaccine Research and DevelopmentRSVpreF Elicits Maternal Neutralizing Titer with GMR >12 at Delivery*
Phase 2bCombined A/B 50% Neutralization Geometric Mean Titers & Geometric Mean Ratio vs. Placebo – in Maternal Participants at
Baseline (24- 36 weeks GA), 1M(if Delivery had not Occurred), Delivery and Postpartum; All Evaluable (N=116 participants)
10100100010000100000
Baseline 1 Month Delivery 6 Months Postpartum50% Neutralizing GMT
Placebo 120 μ g17.8
12.4 5.4
Lower Limit of Quantification (L LOQ), RSV A LLOQ , RSV B*Mean time from vaccination to delivery, 61.4 days
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Vaccine Research and DevelopmentTransplacental Transfer Ratios >1 Overall and by Geography and
Gestational Age
Combined RSV A/B 50% Neutralization Antibody Infant v. Maternal Ratio for Phase 3 selected dose
Evaluable Population, RSVpreF Groups (N=99)
0.1110
RSV A/B, All
(n=99)Northern
Hemisphere
(n=88)Southern
Hemisphere
(n=11)GA 24 to <27
(n=21)GA 27 to <30
(n=26)GA 30 to <33
(n=26)GA 33 to 36
(n=26)Neutralizing Titer Transfer Ratio
Geography Maternal Gestational Age at Vaccination
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Vaccine Research and DevelopmentRSV A/B Combined 50% Geometric Mean Neutralizing Titers by Month in Infants born to Mothers Vaccinated at 24-36 weeksInfant Neutralizing Titers Remain High Through 6 Months
100100010000100000
0 1 2 3 4 5 6 7RSV A/B Combined Serum Neutralizing
Titer
MonthsRSVpreF 120 μ g
Placebo
Palivizumab reference
---Palivizumab reference line = 50% A/B neutralizing titer of a 100ug/mL palivizumab dose, demonstrated to be efficacious in preventing infant RSV-
associated ICU admission (Forbes ML, Kumar VR, Yogev R, et al. Hum Vaccin Immunother 2014;10:2789 -94.)
185Worldwide Research, Development and Medical
Vaccine Research and Development2018 2019 2020 2021 2022+
Phase 1/2
First -in-Human1Adults 18- 85y
Dose Ranging
+/-Al(OH)3 +/-Influenza
Phase 2b2Pregnant Women 18–49y
Safety and ImmunogenicityEarly Efficacy
Phase 2b
3 Nonpregnant Women 18- 49y
Concomitant Tdap
Phase 34 Adults 18- 49y
Lot Consistency Study
Phase 35 Pregnant Women ≤49y
Pivotal Efficacy
1. A Study to Describe the Safety and Immunogenicity of a RSV Vaccine in Healthy Adults. NCT03529773.
2. A Phase 2bPlacebo- Controlled, Randomized Study of an RSV Vaccine in Pregnant Women. NCT04032093.
3. A Study of an RSV Vaccine When Given Together with Tdap in Healthy Nonpregnant Women Aged Between 18 to 49 Years. NCT04071158.
4. Clinical Lot Consistency for RSVpreF in a Population of Healthy Adults 18 to ≤49 Years of Age. NCT05096208.
5. A Trial to Evaluate the Efficacy and Safety of RSVpreF in Infants Born to Women Vaccinated During Pregnancy. NCT04424316 .Pfizer’s RSVpreF Maternal Immunization Clinical Development Program
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Vaccine Research and DevelopmentA Trial to Evaluate the Efficacy and Safety of RSVpreF in Infants Born to Women Vaccinated During Pregnancy. NCT04424316.MATISSE: A Phase 3 Trial to Evaluate the Efficacy and Safety of RSVpreF in
Infants Born to Women Vaccinated During Pregnancy
7,392 Maternal Participants in 18 Countries
Randomized 1:1 RSVpreF 120µg or Placebo
Pregnant persons ≤49 years between
≥24 and ≤36 weeks gestation
7,128 Infants enrolled
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Vaccine Research and Development
AEs from Consent to 28 Days
a. Screening bloods and fetal anomaly ultrasound (if not standard of care); ROW, Rest of World
b. Fetal dating and dating ultrasounds (if not standard of care).
c. AESI (AE of Special Interest including preterm delivery and asymptomatic SARS -CoV -2 test positive).Maternal Immunogenicity & Safety Assessment Timeline
AESIc, SAEs : Consent to End of Study
7 days e-diary
Screening
Philippines & Africab
Screening
ROWa
Day -90 Day -28 Day 1 Day 7 Day 28 Variable Duration Delivery 6-Months Post Delivery
RTI surveillance : All MA -RTI Events Captured as Endpoints from Vaccination to End of Study
Pre-Screening
Pre-vaccination
Vaccination
Visit 1
1-Month Follow- up
Visit 2
Labor & Delivery
Visit 3
Maternal Follow- Up
Visit 4
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Vaccine Research and Development
AEs for 28 Days
Infant Efficacy, Immunogenicity & Safety Assessment Timeline
AESI, SAEs and NDCMCs: Birth to End of Study
Birth Day 1 28 Days After 6-mo 12-Mo 24-Mo
Delivery & Infant RTI Surveillance Period*
*Starts 72 hours after delivery
18-Mo
Visit 1
Visit 2
Visit 3
12-Mo Follow- up
for All Infants
24-mo Follow- up for Infants
Born in Study -year 1
Cord
Blood
Weekly contact with mother /
RTI site visit + nasal swabs for MA -RTI
Monthly contact with mother / RTI hospitalization
& severe LRTI requires RTI visit + nasal swabs
RTISurveillance (e-dairy)
Visit 4
Visit 5
Visit 6
AESI (AE of Special Interest including preterm birth, low birth weight, developmental delay, and asymptomatic SARS -CoV -2 test positive)
SAE (Serious Adverse Event)
NDCMC (Newly Diagnosed Chronic Medical Condition)
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Vaccine Research and Developmenta. N = number of participants in the specified vaccine group. This value is the denominator for the percentage calculations.
b. n = Number of participants in the specified category. Demographic Characteristics
(Maternal Safety Population)
RSVpreF 120 μg
(Na=3682) ; n (%)Placebo
(Na=3675) ; n (%)Total
(Na=7357) ; n (%)
Race
White 2383 (64.7) 2365 (64.4) 4748 (64.5)
Black or African American 720 (19.6) 723 (19.7) 1443 (19.6)
Asian 454 (12.3) 464 (12.6) 918 (12.5)
American Indian or Alaskan Native 38 (1.0) 37 (1.0) 75 (1.0)
Native Hawaiian or Other Pacific Islander 9 (0.2) 12 (0.3) 21 (0.3)
Multiracial 30 (0.8) 21 (0.6) 51 (0.7)
Ethnicity
Hispanic/Latino 1049 (28.5) 1075 (29.3) 2124 (28.9)
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Vaccine Research and Development*Average GA at vaccination = 30 weeks
Note: One participant is counted under ≥24 weeks to <28 weeks however actual age was 23 weeks 6 days.
a. N = number of participants in the specified vaccine group. This value is the denominator for the percentage calculations.
b. n = Number of participants in the specified category. Demographic Characteristics (continued 2/2)
(Maternal Safety Population)
RSVpreF 120 μg
(Na=3682) ; n (%)Placebo
(Na=3675) ; n (%)Total
(Na=7357) ; n (%)
Age at Vaccination (years)
N 3682 3675 7357
Mean (SD) 29.1 (5.64) 29.0 (5.74) 29.0 (5.69)
Median (Range) 29.0 (16– 45) 29.0 (14– 47) 29.0 (14– 47)
Gestational Age (GA) at Vaccination*
≥24 weeks to <28 weeks 941 (25.6) 909 (24.7) 1850 (25.1)
≥28 weeks to <32 weeks 1085 (29.5) 1128 (30.7) 2213 (30.1)
≥32 weeks to ≤36 weeks 1653 (44.9) 1632 (44.4) 3285 (44.7)
>36 weeks 3 (<0.1) 6 (0.2) 9 (0.1)
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Vaccine Research and DevelopmentDemographic Characteristics
(Infant Safety Population)
RSVpreF 120 μg
(Na=3568); n (%)Placebo
(Na=3558) ; n (%)Total
(Na=7126) ; n (%)
Sex
Male 1816 (50.9) 1793 (50.4) 3609 (50.6)
Female 1752 (49.1) 1765 (49.6) 3517 (49.4)
Race
White 2294 (64.3) 2284 (64.2) 4578 (64.2)
Black or African American 687 (19.3) 688 (19.3) 1375 (19.3)
Asian 420 (11.8) 430 (12.1) 850 (11.9)
American Indian or Alaskan Native 42 (1.2) 36 (1.0) 78 (1.1)
Native Hawaiian or other Pacific Islander 13 (0.4) 11 (0.3) 24 (0.3)
Multiracial 65 (1.8) 59 (1.7) 124 (1.7)
Ethnicity
Hispanic/Latino 1033 (29.0) 1039 (29.2) 2072 (29.1)
a.N = number of participants in the specified vaccine group. This value is the denominator for the percentage calculations.
b.n = Number of participants in the specified category.
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Vaccine Research and DevelopmentPhase 3 Study Objectives
Safety•Describe the safety profile of RSVpreF
Local reactions and systemic events within 7 days post -vaccination
AEs through 1-month post -vaccination (Maternal)
AEs through 1-month after birth (Infant)
AESIs , SAEs (Maternal and Infant) and NDCMCs (Infant) throughout study
EfficacyPrimary•Prevention of RSV MA -LRTI within 180 days after birth
•Prevention of RSV severe MA -LRTI within 180 days after birth
Secondary•Prevention of RSV MA -LRTIs within 360 days after birth
•Prevention of RSV hospitalization within 360 days after birth
•Prevention of MA -LRTIs due to any cause within 360 days after birth
AE, adverse event; AESI, adverse event of special interest; NDCMC, newly diagnosed chronic medical condition; SAE, serious adver se event;
MA, medically attended; LRTI, lower respiratory tract illness; RSV, respiratory syncytial virus
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Vaccine Research and Development7.2%
0.2%6.2%
0.2%40.6%
10.1%
0102030405060708090100
RSVpreF
120µgPlacebo RSVpreF
120µgPlacebo RSVpreF
120µgPlacebo% of Subjects
Vaccine Group (as Administered)
Mild Moderate SevereLocal Reactions, by Maximum Severity, within 7 Days After Vaccination
Maternal Participants (n=7357)
Induration/Swelling Pain at Injection Site Erythema/Redness
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Vaccine Research and Development2.6% 2.9%46.1%43.8%
31.0%27.6%
20.0% 19.2%26.5%
17.1%
11.6% 10.5%7.8% 7.0%11.2% 11.5%
0102030405060708090100
RSVpreF
120µgPlacebo RSVpreF
120µgPlacebo RSVpreF
120µgPlacebo RSVpreF
120µgPlacebo RSVpreF
120µgPlacebo RSVpreF
120µgPlacebo RSVpreF
120µgPlacebo RSVpreF
120µgPlacebo% of Subjects
Vaccine Group (as Administered)
Mild or 38.0°C to 38.4°C Moderate or 38.5°C to 38.9°C Severe or 39.0°C to 40.0°C >40°CSystemic Events, by Maximum Severity, Within 7 Days After Vaccination
Maternal Participants (n=7357)
Fatigue Headache Muscle Pain Diarrhea Nausea Fever Joint Pain Vomiting
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Vaccine Research and DevelopmentAbbreviations: AESIs = adverse events of special interest; NDCMCs = newly diagnosed chronic medical conditions.
Notes: The severity of the event is in the determination of the investigator. Per statistical analysis plan, 1 month after bi rthor 1 month after vaccination reflects a 30- day period. However, as per protocol, non- serious adverse events were only solicited
through 28 days after birth/vaccination. AESIs and SAEs were solicited throughout the study for maternal participants.a. N = number of participants in the specified vaccine group. This value is the denominator for the percentage calculations. b. n = Number of participants reporting at least 1 occurrence of the specified adverse event. For "any event", n = number of
participants reporting at least 1 occurrence of any adverse event. c. Exact 2- sided confidence interval (CI) calculated using the Clopper and Pearson method. d. An immediate AE is defined as any AE that occurred within the first 30 minutes after
administration of the investigational product for maternal participants.Number (%) of Participants Reporting Adverse Events by Category
Within 1 Month After Vaccination
Maternal Participantsa,b,c
13.8
4.2
<0.11.7 0.5 0.42.70.013.1
3.7<0.1 1.3 0.3 0.22.50.0
0102030405060708090100
Any AE Serious AE Immediate AEᵈ Severe AE Life-threatening
AERelated AESIs AE Leading to
WithdrawalParticipants
Reporting ≥ AE %RSVpreF 120 μg
(N=3682)
Placebo
(N=3675)
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Vaccine Research and DevelopmentAbbreviations: AESIs = adverse events of special interest; NDCMCs = newly diagnosed chronic medical conditions.
Notes: The severity of the event is in the determination of the investigator. Per statistical analysis plan, 1 month after bi rthor 1 month after vaccination reflects a 30- day period. However, as per protocol, non- serious adverse events were only solicited
through 28 days after birth/vaccination. AESIs and SAEs were solicited throughout the study for maternal participants.a. N = number of participants in the specified vaccine group. This value is the denominator for the percentage calculations. b. n = Number of participants reporting at least 1 occurrence of the specified adverse event. For "any event", n = number of
participants reporting at least 1 occurrence of any adverse event. c. Exact 2- sided confidence interval (CI) calculated using the Clopper and Pearson method. d. An immediate AE is defined as any AE that occurred within the first 30 minutes after
administration of the investigational product for maternal participants.Number (%) of Participants Reporting Adverse Events by Category
Within 1 Month After Birth
Infant Participantsa,b,c
37.1
15.5
4.51.0 <0.18.44.8
0.2 0.034.5
15.2
3.81.0 0.07.2 5.9
0.2 0.0
0102030405060708090100
Any AE Serious AE Severe AE Life-threatening
AERelated AESIs Congenital
AnomaliesNDCMCs AE Leading to
WithdrawalParticipants
Reporting ≥ AE %RSVpreF 120 μg
(N=3568)
Placebo
(N=3558)
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Vaccine Research and DevelopmentBirth Outcomes and Developmental Delay – Infant Participants
Infant Participants with Prematurity, Low Birth Weight, or Developmental Delay (Adverse Events of Special Interest)
0.65.6
0.15.1
0.3 0.34.7
0.24.4
0.3
0102030405060708090100
Early Premature
≤ 34 weeksTotal Premature
≤ 37 weeksVery Low Birth Weight
< 1500gLow Birth Weight
<2500gDevelopmental Delay% ParticipantsRSVpreF
(N=3568)
Placebo(N=3558)
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Vaccine Research and DevelopmentDeaths and Fetal Losses Reported in the Trial (all unrelated)
Event TypeRSVpreF 120 μg
(N=3682)Placebo
(N=3675)
Maternal Death: n = 1
•1 in a maternal participant who received RSVpreF Maternal Death 1 (<0.1%) 0
Fetal Demise: n = 18
•18 fetal demises in maternal participants who received
Vaccine/PlaceboFetal death or stillbirth 10 (0.3%) 8 (0.2%)
Event TypeRSVpreF 120 μg
(N=3568)Placebo
(N=3558)
Infant Death: n = 17
•16 due to various causes
•1 infant adjudicated “Acute Respiratory Illness due to RSV” (placebo group)Infant Death 5 (0.1%) 12 (0.3%)
199 Breakthroughs that change patients’ livesMATISSE
Infant Efficacy Endpoints
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Vaccine Research and DevelopmentC3671008: https://clinicaltrials.gov/ct2/show/NCT04424316?term=C3671008&draw=2&rank=1Phase 3 Efficacy Endpoints Defined
Primary Endpoints Criteria
Medically attended
RSV LRTIMedically attended visit and ≥1 :
•tachypnea (RR ≥60 (<2 m [60 days]) or ≥50 (≥2 to 12 m)
•peripheral capillary oxygen saturation (SpO2) measured in room air <95%
•chest wall indrawing
Medically attended
severe RSV LRTIMedically attended visit and ≥1 :
•tachypnea (RR ≥70 (<2 m [60 days]) or ≥60 (≥2 to 12 m)
•SpO2 measured in room air <93%
• high- flow nasal cannula or mechanical ventilation
•ICU admission for >4 hours; unresponsive/unconsciousPositive
validated
RT-PCR
in central
laboratoryWeekly active surveillance for ARI symptoms
Symptoms trigger nasal swab and possibly a visit
Medically attended visit: Infant participant taken to or seen by a healthcare provider (e.g. outpatient or inpatient visit, emer gency room, urgent care, or home visit)
LRTI : Lower respiratory tract illness; SpO2: peripheral capillary oxygen saturation
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Vaccine Research and DevelopmentRSV-Positive MA -LRTI
Time Interval Number of Cases (%) Number of Cases (%) Vaccine Efficacyb(%) (CI*)
90 Days after birth 24 (0.7) 56 (1.6) 57.1 (14.7, 79.8)
120 Days after birth 35 (1.0) 81 (2.3) 56.8 (31.2, 73.5)
150 Days after birth 47 (1.3) 99 (2.8) 52.5 (28.7, 68.9)
180 Days after birth 57 (1.6) 117 (3.4) 51.3 (29.4, 66.8)Maternal Vaccine Group (as Randomized)
RSV-Positive Severe MA -LRTIRSVpreF 120 μg
(Na=3495)Placebo
(Na=3480)
Time Interval Number of Cases (%) Number of Cases (%) Vaccine Efficacyb(%) (CI*)
90 Days after birth 6 (0.2) 33 (0.9) 81.8 (40.6, 96.3)
120 Days after birth 12 (0.3) 46 (1.3) 73.9 (45.6, 88.8)
150 Days after birth 16 (0.5) 55 (1.6) 70.9 (44.5, 85.9)
180 Days after birth 19 (0.5) 62 (1.8) 69.4 (44.3, 84.1)Vaccine Efficacy by Cumulative Days after Birth for Two Primary Endpoints
*99.5% CI for 90 days, 97.58% CI for 120/150/180 days. CI LB >20% for all time points.
Abbreviations: RSV = respiratory syncytial virus. a. N = number of participants (at risk) in the specified group. These values a re used as the denominators for the percentage calculations. b. Vaccine efficacy was
calculated as 1- (P/[1- P]), where P is the number of cases in the RSVpreF group divided by the total number of cases. The confide nce interval was adjusted using Bonferroni procedure and accounting for the primary
endpoints results.Primary Endpoints:
202Worldwide Research, Development and Medical
Vaccine Research and DevelopmentAbbreviations: MA -LRTI = medically attended lower respiratory tract illness; RSV = respiratory syncytial virus.
a. N = number of participants (at risk) in the specified group. These values are used as the denominators for the percentage calculations.
b. Vaccine efficacy was calculated as 1- (P/[1- P]), where P is the number of cases in the RSVpreF group divided by the total number of cases. The confidence interval was adjusted using Bonferroni procedure and accounting for the primary endpoints results.Secondary Endpoint: RSV -Positive MA-LRTIs within 360 Days After Birth
Maternal Vaccine Group (as Randomized)
RSVpreF 120 μg
(Na=3495)Placebo
(Na=3480)
Time Interval Number of Cases (%) Number of Cases (%) Vaccine Efficacyb(%) (99.17% CI)
210 Days after birth 70 (2.0) 127 (3.6) 44.9 (17.9, 63.5)
240 Days after birth 76 (2.2) 133 (3.8) 42.9 (16.1, 61.6)
270 Days after birth 82 (2.3) 137 (3.9) 40.1 (13.0, 59.2)
360 Days after birth 92 (2.6) 156 (4.5) 41.0 (16.2, 58.9)RSV-Positive MA -LRTIs Occurring Within 360 Days After Birth Met Statistical Criteria for Success
(CI LB>0%)
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Vaccine Research and DevelopmentMaternal Vaccine Group (as Randomized)
RSVpreF 120 μg
(Na=3495)Placebo
(Na=3480)
Time Interval Number of Cases (%) Number of Cases (%) Vaccine Efficacyb(%) (99.17% CI)
90 Days after birth 10 (0.3) 31 (0.9) 67.7 (15.9, 89.5)
180 Days after birth 19 (0.5) 44 (1.3) 56.8 (10.1, 80.7)
360 Days after birth 38 (1.1) 57 (1.6) 33.3 (- 17.6, 62.9)
Abbreviations: EAC = endpoint adjudication committee; RSV = respiratory syncytial virus.
a. N = number of participants (at risk) in the specified group. These values are used as the denominators for the percentage calculations.
b. Vaccine efficacy was calculated as 1- (P/[1-P]), where P is the number of cases in the RSVpreF group divided by the total number of cases. The confidence interval was adjusted using Bonferroni procedure and accounting for the primary endpoints results.Secondary Endpoint: Hospitalizations Due to RSV within 360 Days
After Birth
Hospitalizations Due to RSV through 180 days Met Statistical Criteria for Success (CI LB>0%)
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Vaccine Research and DevelopmentAbbreviations: EAC = endpoint adjudication committee; MA -RTI = medically attended respiratory tract illness; RSV = respiratory s yncytial virus.
a. N = number of participants (at risk) in the specified group. These values are used as the denominators for the percentage calculations.
b. Vaccine efficacy was calculated as 1- (P/[1- P]), where P is the number of cases in the RSVpreF group divided by the total number of cases.Exploratory Endpoint: RSV -Positive MA-RTIs (EAC confirmed) within
180 Days After Birth
Maternal Vaccine Group (as Randomized)
RSVpreF 120 μg
(Na=3495)Placebo
(Na=3480)
Time Interval Number of Cases (%) Number of Cases (%) Vaccine Efficacyb(%) (95% CI)
90 Days after birth 67 (1.9) 110 (3.2) 39.1 (16.7, 55.7)
180 Days after birth 157 (4.5) 253 (7.3) 37.9 (24.0, 49.5)RSV-Positive MA -RTIs through 180 Days After Birth
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Vaccine Research and DevelopmentConsistent efficacy Was Observed Across RSV Subgroup A and B*
RSV Severe MA -LRTI
90, 180 Days
RSV MA -LRTI
90, 180 Days90 Days
180 Days
90 Days
180 DaysCase Split
(RSVpreF/Placebo) VE
6:33 81.8%
4:8 50.0%
2:25 92.0%
19:62 69.4%
7:14 50.0%
11:44 75.0%
Case Split
(RSVpreF/Placebo) VE
24:56 57.1%
8:12 33.3%
17:43 60.5%
57:117 51.3%
19:26 26.9%
38:87 56.3%Vaccine Efficacy (%) (95% CI)
Vaccine Efficacy (%) (95% CI)-100 -50 0 50 100RSV-BRSV-AOverallRSV-BRSV-AOverall
-100 -50 0 50 100RSV-BRSV-AOverallRSV-BRSV-AOverall
* Exploratory Endpoint –no prespecified criterion for RSV A and B
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Vaccine Research and DevelopmentRSVpreF Efficacious Against Severe Infant MA- LRTI in Phase 3 with a
Favorable Safety Profile
RSV = Respiratory Syncytial Virus; IA: Interim Analysis; MATISSE: MAT ernal Immunization Study for S afety and Efficacy; MA-LRTI: Medically Attended Lower Respiratory Tract Illness; CI: Confidence Interval;
DMC: Data Monitoring Committee; BLA: Biologics License Application; FDA: Food and Drug Administration
Source: Pfizer Press release, Oct 31, 2022Time Period Vaccine Efficacy
First 90 days of life* 81.8% (CI: 40.6%, 96.3%)
Six-month follow -up* 69.4% (CI: 44.3%, 84.1%)
Time Period Vaccine Efficacy
First 90 days of life* 57.1% (CI: 14.7%, 79.8%)
Six-month follow -up* 51.3% (CI: 29.4%, 66.8%)Primary Endpoint: Severe MA -LRTI
Primary Endpoint: MA -LRTI
RSVpreF investigational vaccine was well -tolerated with a favorable benefit -risk profile for the
maternal populations and their newborns.*Confidence intervals are 99.5% CI at 90 days and 97.58% CI at later intervals.
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Vaccine Research and Development•The participants and their families
•The study investigators, nurses, coordinators, and laboratory personnel
•Pfizer essential colleagues and our vendorsThanks to