Study 1 (NCT04424316) is a Phase 3 study that assessed the efficacy of ABRYSVO in the prevention of RSV-associated lower respiratory tract disease (LRTD) in infants born to individuals vaccinated during pregnancy. The study evaluated the efficacy of ABRYSVO to prevent RSV-associated LRTD and severe RSV-LRTD in infants within 90, 120, 150, and 180 days after birth. Participants were randomized (1:1) to receive ABRYSVO (0.5 mL dose) or placebo (0.5 mL dose containing the same buffer ingredients in the same quantities as in a single dose of ABRYSVO [see Description (11)]). This study includes sites in both the northern and southern hemispheres. Vaccine efficacy (VE) was defined as the relative risk reduction of the endpoints of severe LRTD caused by RSV and LRTD cause by RSV in infants born to individuals who received ABRYSVO compared to infants born to individuals who received placebo. The demographic characteristics of Study 1 are described in Clinical Trials Experience Section 6.1.
Maternal participants were randomized (1:1) to receive ABRYSVO (3,695) or placebo (3,697). RSV-associated LRTD in infants was defined as a medically attended visit with a reverse transcription-polymerase chain reaction (RT-PCR) confirmed RSV illness with one or more of the following respiratory symptoms: tachypnea (respiratory rate ≥60 breaths/minute [<2 months of age], ≥50 breaths/minute [≥2 to 12 months of age], or ≥40 breaths/minute [≥12-24 months of age]); SpO2 measured in room air <95%; chest wall indrawing. RSV-associated severe LRTD was a subset defined as meeting the LRTD RSV criteria plus at least one of the following: tachypnea (respiratory rate ≥70 breaths per minute [<2 months of age], ≥60 breaths per minute [≥2 to 12 months of age], or ≥50 bpm [≥12 to 24 months of age]); SpO2 measured in room air <93%; high-flow nasal cannula or mechanical ventilation (invasive or noninvasive), ICU admission for >4 hours and/or failure to respond/unconscious. Secondary efficacy endpoints included hospitalizations due to RSV.
The VE results met the statistical criterion for success (a CI lower bound >20%) for reducing severe LRTD due to RSV, at all timepoints to within 180 days. The VE results did not meet the statistical criterion for success (a CI lower bound >20%) for reducing LRTD due to RSV; however, clinically meaningful efficacy was observed after 90 days through 180 days after birth.
Vaccine efficacy information is presented in Tables 6 to 10.
| CI - confidence interval; N – number of participants; RSV – respiratory syncytial virus; VE - vaccine efficacy | |||
Time Period | ABRYSVO Number of Cases N=3,495† | PLACEBO Number of Cases N=3,480† | VE (%) (CI)‡ |
90 days | 6 | 33 | 81.8 (40.6, 96.3) |
120 days | 12 | 46 | 73.9 (45.6, 88.8) |
150 days | 16 | 55 | 70.9 (44.5, 85.9) |
180 days | 19 | 62 | 69.4 (44.3, 84.1) |
| CI - confidence interval; N – number of participants; RSV – respiratory syncytial virus; VE - vaccine efficacy | |||
Time Period | ABRYSVO Number of Cases N=3,495† | PLACEBO Number of Cases N=3,480† | VE (%) (CI)‡ |
90 days | 24 | 56 | 57.1 (14.7, 79.8) |
120 days | 35 | 81 | 56.8 (31.2, 73.5) |
150 days | 47 | 99 | 52.5 (28.7, 68.9) |
180 days | 57 | 117 | 51.3 (29.4, 66.8) |
| CI - confidence interval; N – number of participants; n - number of cases; RSV – respiratory syncytial virus; VE - vaccine efficacy | |||
Time Period | ABRYSVO Number of Cases N=1572† | PLACEBO Number of Cases N=1539† | VE (%) (CI)‡ |
90 days | 1 | 11 | 91.1 (38.8, 99.8) |
180 days | 6 | 25 | 76.5 (41.3, 92.1) |
| CI - confidence interval; N – number of participants; n - number of cases; RSV – respiratory syncytial virus; VE - vaccine efficacy | |||
Time Period | ABRYSVO Number of Cases N=1572† | PLACEBO Number of Cases N=1539† | VE (%) (CI)‡ |
90 days | 14 | 21 | 34.7 (-34.6, 69.3) |
180 days | 24 | 55 | 57.3 (29.8, 74.7) |
| CI - confidence interval; N – number of participants; n - number of cases; RSV – respiratory syncytial virus; VE - vaccine efficacy | |||
Time Period | ABRYSVO Number of Cases N=3,495† | PLACEBO Number of Cases N=3,480† | VE (%) (CI)‡ |
90 days | 10 | 31 | 67.7 (15.9, 89.5) |
120 days | 15 | 37 | 59.5 (8.3, 83.7) |
150 days | 17 | 39 | 56.4 (5.2, 81.5) |
180 days | 19 | 44 | 56.8 (10.1, 80.7) |
Study 3 (NCT05035212) is an ongoing Phase 3, multicenter, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of ABRYSVO in the prevention of RSV-associated lower respiratory tract disease in individuals 60 years of age and older. Participants are planned to be followed for up to two RSV seasons, approximately 25 months.
Participants were randomized (1:1) to receive ABRYSVO (n=17,197) or placebo (n=17,186). Randomization was stratified by age, 60-69 years (n=21,499, 63%), 70-79 years (n=10,948, 32%), and ≥80 years (n=1,934, 6%). Healthy adults and adults with stable chronic diseases were included. Among enrolled participants 15% had stable chronic cardiopulmonary conditions such as chronic obstructive pulmonary disease (COPD), asthma, or congestive heart failure (CHF).
Starting 14 days after study vaccination (study Day 15), all participants were actively monitored for onset of acute respiratory illness (ARI) symptoms: new or increased sore throat, nasal congestion, nasal discharge, cough, wheezing, sputum production, or shortness of breath. If the participant experienced 1 or more ARI symptoms, a mid-turbinate nasal swab was collected within 7 days of onset of symptoms and tested by reverse transcriptase polymerase chain reaction (RT-PCR) for RSV.
RSV-associated lower respiratory tract disease (RSV-LRTD) was evaluated in Study 3. A case of RSV-LRTD was defined as an RT-PCR confirmed RSV illness with two or more, or three or more, of the following respiratory symptoms within 7 days of symptom onset and lasting more than 1 day during the same illness: new or increased cough, wheezing, sputum production, shortness of breath, or tachypnea (≥25 breaths/min or 15% increase from resting baseline). A case of RSV-associated severe lower respiratory tract disease was defined as a case meeting the RSV-LRTD criteria plus at least one of the following: hospitalization due to RSV-LRTD, new or increased oxygen supplementation, or mechanical ventilation including Continuous Positive Airway Pressure (CPAP).
Efficacy against Respiratory Syncytial Virus-associated Lower Respiratory Tract Disease in Individuals 60 Years of Age and Older
Vaccine efficacy (VE), against RSV-LRTD, defined as the relative risk reduction of first episode of RSV-LRTD in the ABRYSVO group compared to the placebo group in the first RSV season, was assessed.
The study met the pre-specified success criteria for demonstration of efficacy of ABRYSVO for the primary objectives of prevention of RSV-LRTD with ≥2 symptoms and prevention of RSV-LRTD with ≥3 symptoms. The median duration of follow-up for efficacy was 7 months.
Vaccine efficacy information is presented in Table 11.
| CI – confidence interval; N – number of participants; n = number of cases; RSV – respiratory syncytial virus; VE – vaccine efficacy (VE based on case count ratio is calculated as 1-(P/[1-P]), where P is the number of RSVpreF cases divided by the total number of cases) | |||
Efficacy Endpoint | ABRYSVO N=16,306† n | Placebo N=16,308† n | VE (%) (96.66% CI) |
First episode of RSV-associated lower respiratory tract disease with ≥2 symptoms | 11 | 33 | 66.7 (28.8, 85.8) |
First episode of RSV-associated lower respiratory tract disease with ≥3 symptoms | 2 | 14 | 85.7 (32.0, 98.7) |
There were 2 cases of RSV-associated severe lower respiratory tract disease in the placebo group and no cases in the ABRYSVO group.
Study 4 (NCT04071158) was a Phase 2, placebo-controlled, randomized, observer-blind study to evaluate the safety, tolerability, and immunogenicity of ABRYSVO (at dose levels 120 µg and 240 µg, with or without Al(OH)3) when administered concomitantly with Tdap in non-pregnant women 18 through 49 years of age.
Antibody responses to antigens contained in ABRYSVO and Tdap were assessed 1 month after vaccination in a population of non-pregnant adult individuals. Lower geometric mean antibody concentrations (GMCs) to the acellular pertussis antigens (pertussis toxin [PT], filamentous hemagglutinin (FHA), and pertactin [PRN]) were observed when ABRYSVO was administered concomitantly with a tetanus, diphtheria and acellular pertussis vaccine (Tdap) compared to pertussis GMCs when Tdap was administered alone. The lower limit (LL) of the 2-sided 95% confidence interval of the GMC ratio (GMC ABRYSVO+Tdap /GMC Tdap) was 0.64 for PT, 0.50 for FHA, and 0.48 for PRN, which did not meet the pre-specified non-inferiority criterion (lower limit of the 95% confidence interval for the GMC ratio is >0.67). The clinical relevance of this finding is unknown. The non-inferiority criteria for tetanus, diphtheria and RSV vaccine antigens were met [see Drug Interactions (7)].
Study 1 (NCT04424316) is a Phase 3 study that assessed the efficacy of ABRYSVO in the prevention of RSV-associated lower respiratory tract disease (LRTD) in infants born to individuals vaccinated during pregnancy. The study evaluated the efficacy of ABRYSVO to prevent RSV-associated LRTD and severe RSV-LRTD in infants within 90, 120, 150, and 180 days after birth. Participants were randomized (1:1) to receive ABRYSVO (0.5 mL dose) or placebo (0.5 mL dose containing the same buffer ingredients in the same quantities as in a single dose of ABRYSVO [see Description (11)]). This study includes sites in both the northern and southern hemispheres. Vaccine efficacy (VE) was defined as the relative risk reduction of the endpoints of severe LRTD caused by RSV and LRTD cause by RSV in infants born to individuals who received ABRYSVO compared to infants born to individuals who received placebo. The demographic characteristics of Study 1 are described in Clinical Trials Experience Section 6.1.
Maternal participants were randomized (1:1) to receive ABRYSVO (3,695) or placebo (3,697). RSV-associated LRTD in infants was defined as a medically attended visit with a reverse transcription-polymerase chain reaction (RT-PCR) confirmed RSV illness with one or more of the following respiratory symptoms: tachypnea (respiratory rate ≥60 breaths/minute [<2 months of age], ≥50 breaths/minute [≥2 to 12 months of age], or ≥40 breaths/minute [≥12-24 months of age]); SpO2 measured in room air <95%; chest wall indrawing. RSV-associated severe LRTD was a subset defined as meeting the LRTD RSV criteria plus at least one of the following: tachypnea (respiratory rate ≥70 breaths per minute [<2 months of age], ≥60 breaths per minute [≥2 to 12 months of age], or ≥50 bpm [≥12 to 24 months of age]); SpO2 measured in room air <93%; high-flow nasal cannula or mechanical ventilation (invasive or noninvasive), ICU admission for >4 hours and/or failure to respond/unconscious. Secondary efficacy endpoints included hospitalizations due to RSV.
The VE results met the statistical criterion for success (a CI lower bound >20%) for reducing severe LRTD due to RSV, at all timepoints to within 180 days. The VE results did not meet the statistical criterion for success (a CI lower bound >20%) for reducing LRTD due to RSV; however, clinically meaningful efficacy was observed after 90 days through 180 days after birth.
Vaccine efficacy information is presented in Tables 6 to 10.
| CI - confidence interval; N – number of participants; RSV – respiratory syncytial virus; VE - vaccine efficacy | |||
Time Period | ABRYSVO Number of Cases N=3,495† | PLACEBO Number of Cases N=3,480† | VE (%) (CI)‡ |
90 days | 6 | 33 | 81.8 (40.6, 96.3) |
120 days | 12 | 46 | 73.9 (45.6, 88.8) |
150 days | 16 | 55 | 70.9 (44.5, 85.9) |
180 days | 19 | 62 | 69.4 (44.3, 84.1) |
| CI - confidence interval; N – number of participants; RSV – respiratory syncytial virus; VE - vaccine efficacy | |||
Time Period | ABRYSVO Number of Cases N=3,495† | PLACEBO Number of Cases N=3,480† | VE (%) (CI)‡ |
90 days | 24 | 56 | 57.1 (14.7, 79.8) |
120 days | 35 | 81 | 56.8 (31.2, 73.5) |
150 days | 47 | 99 | 52.5 (28.7, 68.9) |
180 days | 57 | 117 | 51.3 (29.4, 66.8) |
| CI - confidence interval; N – number of participants; n - number of cases; RSV – respiratory syncytial virus; VE - vaccine efficacy | |||
Time Period | ABRYSVO Number of Cases N=1572† | PLACEBO Number of Cases N=1539† | VE (%) (CI)‡ |
90 days | 1 | 11 | 91.1 (38.8, 99.8) |
180 days | 6 | 25 | 76.5 (41.3, 92.1) |
| CI - confidence interval; N – number of participants; n - number of cases; RSV – respiratory syncytial virus; VE - vaccine efficacy | |||
Time Period | ABRYSVO Number of Cases N=1572† | PLACEBO Number of Cases N=1539† | VE (%) (CI)‡ |
90 days | 14 | 21 | 34.7 (-34.6, 69.3) |
180 days | 24 | 55 | 57.3 (29.8, 74.7) |
| CI - confidence interval; N – number of participants; n - number of cases; RSV – respiratory syncytial virus; VE - vaccine efficacy | |||
Time Period | ABRYSVO Number of Cases N=3,495† | PLACEBO Number of Cases N=3,480† | VE (%) (CI)‡ |
90 days | 10 | 31 | 67.7 (15.9, 89.5) |
120 days | 15 | 37 | 59.5 (8.3, 83.7) |
150 days | 17 | 39 | 56.4 (5.2, 81.5) |
180 days | 19 | 44 | 56.8 (10.1, 80.7) |
Study 3 (NCT05035212) is an ongoing Phase 3, multicenter, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of ABRYSVO in the prevention of RSV-associated lower respiratory tract disease in individuals 60 years of age and older. Participants are planned to be followed for up to two RSV seasons, approximately 25 months.
Participants were randomized (1:1) to receive ABRYSVO (n=17,197) or placebo (n=17,186). Randomization was stratified by age, 60-69 years (n=21,499, 63%), 70-79 years (n=10,948, 32%), and ≥80 years (n=1,934, 6%). Healthy adults and adults with stable chronic diseases were included. Among enrolled participants 15% had stable chronic cardiopulmonary conditions such as chronic obstructive pulmonary disease (COPD), asthma, or congestive heart failure (CHF).
Starting 14 days after study vaccination (study Day 15), all participants were actively monitored for onset of acute respiratory illness (ARI) symptoms: new or increased sore throat, nasal congestion, nasal discharge, cough, wheezing, sputum production, or shortness of breath. If the participant experienced 1 or more ARI symptoms, a mid-turbinate nasal swab was collected within 7 days of onset of symptoms and tested by reverse transcriptase polymerase chain reaction (RT-PCR) for RSV.
RSV-associated lower respiratory tract disease (RSV-LRTD) was evaluated in Study 3. A case of RSV-LRTD was defined as an RT-PCR confirmed RSV illness with two or more, or three or more, of the following respiratory symptoms within 7 days of symptom onset and lasting more than 1 day during the same illness: new or increased cough, wheezing, sputum production, shortness of breath, or tachypnea (≥25 breaths/min or 15% increase from resting baseline). A case of RSV-associated severe lower respiratory tract disease was defined as a case meeting the RSV-LRTD criteria plus at least one of the following: hospitalization due to RSV-LRTD, new or increased oxygen supplementation, or mechanical ventilation including Continuous Positive Airway Pressure (CPAP).
Efficacy against Respiratory Syncytial Virus-associated Lower Respiratory Tract Disease in Individuals 60 Years of Age and Older
Vaccine efficacy (VE), against RSV-LRTD, defined as the relative risk reduction of first episode of RSV-LRTD in the ABRYSVO group compared to the placebo group in the first RSV season, was assessed.
The study met the pre-specified success criteria for demonstration of efficacy of ABRYSVO for the primary objectives of prevention of RSV-LRTD with ≥2 symptoms and prevention of RSV-LRTD with ≥3 symptoms. The median duration of follow-up for efficacy was 7 months.
Vaccine efficacy information is presented in Table 11.
| CI – confidence interval; N – number of participants; n = number of cases; RSV – respiratory syncytial virus; VE – vaccine efficacy (VE based on case count ratio is calculated as 1-(P/[1-P]), where P is the number of RSVpreF cases divided by the total number of cases) | |||
Efficacy Endpoint | ABRYSVO N=16,306† n | Placebo N=16,308† n | VE (%) (96.66% CI) |
First episode of RSV-associated lower respiratory tract disease with ≥2 symptoms | 11 | 33 | 66.7 (28.8, 85.8) |
First episode of RSV-associated lower respiratory tract disease with ≥3 symptoms | 2 | 14 | 85.7 (32.0, 98.7) |
There were 2 cases of RSV-associated severe lower respiratory tract disease in the placebo group and no cases in the ABRYSVO group.
Study 4 (NCT04071158) was a Phase 2, placebo-controlled, randomized, observer-blind study to evaluate the safety, tolerability, and immunogenicity of ABRYSVO (at dose levels 120 µg and 240 µg, with or without Al(OH)3) when administered concomitantly with Tdap in non-pregnant women 18 through 49 years of age.
Antibody responses to antigens contained in ABRYSVO and Tdap were assessed 1 month after vaccination in a population of non-pregnant adult individuals. Lower geometric mean antibody concentrations (GMCs) to the acellular pertussis antigens (pertussis toxin [PT], filamentous hemagglutinin (FHA), and pertactin [PRN]) were observed when ABRYSVO was administered concomitantly with a tetanus, diphtheria and acellular pertussis vaccine (Tdap) compared to pertussis GMCs when Tdap was administered alone. The lower limit (LL) of the 2-sided 95% confidence interval of the GMC ratio (GMC ABRYSVO+Tdap /GMC Tdap) was 0.64 for PT, 0.50 for FHA, and 0.48 for PRN, which did not meet the pre-specified non-inferiority criterion (lower limit of the 95% confidence interval for the GMC ratio is >0.67). The clinical relevance of this finding is unknown. The non-inferiority criteria for tetanus, diphtheria and RSV vaccine antigens were met [see Drug Interactions (7)].
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