ABRYSVO Powder and solvent for solution for injection Ref.[51247] Active ingredients: RSV glycoprotein F antigen

Pharmacotherapeutic group: Vaccines, other viral vaccines
ATC code: J07BX05

Mechanism of action

Abrysvo contains two recombinant stabilised RSV prefusion F antigens representing subgroups RSV-A and RSV-B. Prefusion F is the primary target of neutralising antibodies that block RSV infection. Following intramuscular administration, the prefusion F antigens elicit an immune response, which protects against RSV-associated lower respiratory tract disease.

In infants born to mothers who were vaccinated with Abrysvo between weeks 24 and 36 of gestation, protection against RSV-associated lower respiratory tract disease is due to transplacental transfer of RSV neutralising antibodies. Adults 60 years of age and older are protected by active immunisation.

Clinical efficacy

Infants from birth through 6 months of age by active immunisation of pregnant individuals

Study 1 is a phase 3, multicentre, randomised (1:1), double-blind, placebo-controlled study to assess the efficacy of a single dose of Abrysvo in the prevention of RSV-associated lower respiratory tract disease in infants born to pregnant individuals vaccinated between weeks 24 and 36 of gestation. The need for revaccination with subsequent pregnancies has not been established.

RSV-associated lower respiratory tract illness 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: fast breathing, low oxygen saturation (SpO₂ <95%) and chest wall indrawing. RSV-associated severe lower respiratory tract illness was defined as an illness that met the lower respiratory tract illness-RSV criteria plus at least one of the following: very fast breathing, low oxygen saturation (SpO₂ <93%), high-flow oxygen supplementation via nasal cannula or mechanical ventilation, ICU admission for >4 hours and/or failure to respond/unconscious.

In this study, 3 695 pregnant individuals with uncomplicated, singleton pregnancies were randomised to the Abrysvo group and 3 697 to placebo.

Vaccine efficacy (VE) was defined as the relative risk reduction of the endpoint in the Abrysvo group compared to the placebo group for infants born to pregnant individuals who received the assigned intervention. There were two primary efficacy endpoints, assessed in parallel, severe RSV-positive medically attended lower respiratory tract illness and RSV-positive medically attended lower respiratory tract illness, occurring within 90, 120, 150 or 180 days after birth.

Of the pregnant women who received Abrysvo, 65% were White, 20% were Black or African American and 29% were Hispanic/Latino. The median age was 29 years (range 16-45 years); 0.2% of participants were under 18 years of age and 4.3% were under 20 years of age. The median gestational age at vaccination was 31 weeks and 2 days (range 24 weeks and 0 days to 36 weeks and 4 days). The median infant gestational age at birth was 39 weeks and 1 day (range 27 weeks and 3 days to 43 weeks and 6 days).

Vaccine efficacy is presented in Tables 2 and 3.

Table 2. Vaccine efficacy of Abrysvo against severe medically attended lower respiratory tract illness caused by RSV in infants from birth through 6 months of age by active immunisation of pregnant individuals – Study 1:

CI = confidence interval; VE = vaccine efficacy
^a 99.5% CI at 90 days; 97.58% CI at later intervals

Table 3. Vaccine efficacy of Abrysvo against medically attended lower respiratory tract illness caused by RSV in infants from birth through 6 months of age by active immunisation of pregnant individuals – Study 1:

CI = confidence interval; VE = vaccine efficacy
^a 99.5% CI at 90 days; 97.58% CI at later intervals

A post-hoc analysis of VE by maternal gestational age was conducted. For severe medically attended lower respiratory tract illness occurring within 180 days, VE was 57.2% (95% CI 10.4, 80.9) for women vaccinated early in pregnancy (24 to <30 weeks) and 78.1% (95% CI 52.1, 91.2) for women vaccinated later in the pregnancy eligible window (30 to 36 weeks). For medically attended lower respiratory tract illness occurring within 180 days, VE was 30.9% (95% CI -14.4, 58.9) for women vaccinated early in pregnancy (24 to <30 weeks) and 62.4% (95% CI 41.6, 76.4) for women vaccinated later in the pregnancy eligible window (30 to 36 weeks).

Active immunisation of individuals 60 years of age and older

Study 2 is a phase 3, multicentre, randomised, double-blind, placebo-controlled study to assess the efficacy of Abrysvo in the prevention of RSV-associated lower respiratory tract illness in individuals 60 years of age and older.

RSV-associated lower respiratory tract illness was defined as 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 tachypnoea (≥25 breaths/min or 15% increase from resting baseline).

Participants were randomised (1:1) to receive Abrysvo (n=18 488) or placebo (n=18 479). Enrollment was stratified by age 60-69 years (63%), 70-79 years (32%) and ≥80 years (5%). Subjects with stable chronic underlying conditions were eligible for this study and 52% of participants had at least 1 prespecified condition; 16% of participants were enrolled with stable chronic cardiopulmonary conditions such as asthma (9%), chronic obstructive pulmonary disease (7%) or congestive heart failure (2%). Immunocompromised individuals were ineligible.

The primary objective was assessment of vaccine efficacy (VE), defined as the relative risk reduction of first episode of RSV-associated lower respiratory tract illness in the Abrysvo group compared to the placebo group in the first RSV season.

Of the participants who received Abrysvo, 51% were male and 80% were White, 12% were Black or African American and 41% were Hispanic/Latino. The median age of participants was 67 years (range 59-95 years).

At the end of the first RSV season the analysis demonstrated statistically significant efficacy for Abrysvo for reduction of RSV-associated lower respiratory tract illness with ≥2 symptoms and with ≥3 symptoms.

Vaccine efficacy information is presented in Table 4.

Table 4. Vaccine efficacy of Abrysvo against RSV disease – active immunisation of individuals 60 years of age and older – Study 2:

CI – confidence interval; RSV – respiratory syncytial virus; VE – vaccine efficacy
^a In an exploratory analysis in RSV subgroup A (Abrysvo n=3, placebo n=16 VE was 81.3% (CI 34.5, 96.5); and in RSV subgroup B (Abrysvo n=12, placebo n=26) VE was 53.8% (CI 5.2, 78.8).
^b In an exploratory analysis in RSV subgroup A (Abrysvo n=1, placebo n=5) VE was 80.0% (CI -78.7, 99.6); and in RSV subgroup B (Abrysvo n=1, placebo n=12) VE was 91.7% (CI 43.7, 99.8).

Paediatric population

The European Medicines Agency has deferred the obligation to submit the results of studies with Abrysvo in children from 2 to less than 18 years of age in prevention of lower respiratory tract disease caused by RSV (see section 4.2 for information on paediatric use).