Abrysvo

The powder is white.
The solvent is a clear, colourless liquid.
After reconstitution, one dose (0.5 mL) contains: RSV subgroup A stabilised prefusion F antigen^1,2 60 micrograms, RSV subgroup B stabilised prefusion F antigen^1,2 60 micrograms, (RSV antigens).
¹glycoprotein F stabilised in the prefusion conformation.
²produced in Chinese Hamster Ovary cells by recombinant DNA technology.
Excipients/Inactive Ingredients: Trometamol, Trometamol hydrochloride, Sucrose, Mannitol, Polysorbate 80, Sodium chloride, Water for injections.

Pharmacotherapeutic group: Vaccines, other viral vaccines. ATC code: J07BX05.
Pharmacology: Pharmacodynamics: 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 1 and 2. (See Tables 1 and 2.)

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Click on icon to see table/diagram/image

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 3. (See Table 3.)

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Pharmacokinetics: Not applicable.
Toxicology: Preclinical safety data: Non-clinical data reveal no special hazard for humans based on conventional studies of repeated dose toxicity and toxicity to reproduction and development.

Abrysvo is indicated for: Passive protection against lower respiratory tract disease caused by respiratory syncytial virus (RSV) in infants from birth through 6 months of age following maternal immunisation during pregnancy. See Dosage & Administration and Pharmacology: Pharmacodynamics under Actions.
Active immunisation of individuals 60 years of age and older for the prevention of lower respiratory tract disease caused by RSV.
The use of this vaccine should be in accordance with official recommendations.

Posology: Pregnant individuals: A single dose of 0.5 mL should be administered between weeks 24 and 36 of gestation (see Precautions and Pharmacology: Pharmacodynamics under Actions).
Individuals 60 years of age and older: A single dose of 0.5 mL should be administered.
Paediatric population: The safety and efficacy of Abrysvo in children (from birth to less than 18 years of age) have not yet been established. Limited data are available in pregnant adolescents and their infants (see Pharmacology: Pharmacodynamics under Actions).
Method of administration: Abrysvo is for intramuscular injection into the deltoid region of the upper arm.
The vaccine should not be mixed with any other vaccines or medicinal products.
For instructions on reconstitution and handling of the medicinal product before administration, see Special precautions for disposal and other handling under Cautions for Usage.

Overdose with Abrysvo is unlikely due to its single dose presentation.
There is no specific treatment for an overdose with Abrysvo. In the event of an overdose, the individual should be monitored and provided with symptomatic treatment as appropriate.

Hypersensitivity to the active substances or to any of the excipients listed in Description.

Traceability: In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
Hypersensitivity and anaphylaxis: Appropriate medical treatment and supervision should always be readily available in case of an anaphylactic event following the administration of the vaccine.
Anxiety-related reactions: Anxiety-related reactions, including vasovagal reactions (syncope), hyperventilation or stress-related reactions may occur in association with vaccination as a psychogenic response to the needle injection.
It is important that procedures are in place to avoid injury from fainting.
Concurrent illness: Vaccination should be postponed in individuals suffering from an acute febrile illness. However, the presence of a minor infection, such as a cold, should not result in the deferral of vaccination.
Thrombocytopenia and coagulation disorders: Abrysvo should be given with caution to individuals with thrombocytopenia or any coagulation disorder since bleeding or bruising may occur following an intramuscular administration to these individuals.
Immunocompromised individuals: The efficacy and safety of the vaccine have not been assessed in immunocompromised individuals, including those receiving immunosuppressant therapy. The efficacy of Abrysvo may be lower in immunosuppressed individuals.
Individuals less than 24 weeks of gestation: Abrysvo has not been studied in pregnant individuals less than 24 weeks of gestation. Since protection of the infant against RSV depends on transfer of maternal antibodies across the placenta, Abrysvo should be administered between weeks 24 and 36 of gestation (see Dosage & Administration and Pharmacology: Pharmacodynamics under Actions).
Limitations of vaccine effectiveness: As with any vaccine, a protective immune response may not be elicited after vaccination.
Excipient: This medicinal product contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially 'sodium-free'.
Effects on ability to drive and use machines: Abrysvo has no or negligible influence on the ability to drive and use machines.

Pregnancy: Data on pregnant women (more than 4,000 exposed outcomes) indicate no malformative nor feto/neonatal toxicity.
Results from animal studies with Abrysvo do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see Pharmacology: Toxicology: Preclinical safety data under Actions).
In a phase 3 study (Study 1), maternal adverse events reported within 1 month after vaccination were similar in the Abrysvo group (14%) and the placebo group (13%).
No safety signals were detected in infants up to 24 months of age. The incidences of adverse events reported within 1 month after birth in infants were similar in the Abrysvo group (37%) and the placebo group (35%). Major birth outcomes assessed in the Abrysvo group compared to placebo included premature birth (201 (6%) and 169 (5%), respectively), low birth weight (181 (5%) and 155 (4%), respectively) and congenital anomalies (174 (5%) and 203 (6%), respectively).
Breast-feeding: It is unknown whether Abrysvo is excreted in human milk. No adverse effects of Abrysvo have been shown in breastfed newborns of vaccinated mothers.
Fertility: No human data on the effect of Abrysvo on fertility are available.
Animal studies do not indicate direct or indirect harmful effects with respect to female fertility (see Pharmacology: Toxicology: Preclinical safety data under Actions).

Summary of the safety profile: Pregnant individuals: In pregnant women at 24-36 weeks of gestation the most frequently reported adverse reactions were vaccination site pain (41%), headache (31%) and myalgia (27%). The majority of local and systemic reactions in maternal participants were mild to moderate in severity and resolved within 2-3 days of onset.
Individuals 60 years of age and older: In individuals 60 years of age and older the most frequently reported adverse reaction was vaccination site pain (11%). The majority of reactions were mild to moderate in severity and resolved within 1-2 days of onset.
Tabulated list of adverse reactions: The safety of administering a single dose of Abrysvo to pregnant women at 24-36 weeks of gestation (n=3,682) and to individuals 60 years of age and older (n=18,575) was evaluated in phase 3 clinical trials.
Adverse reactions are listed according to the following frequency categories: Very common (≥1/10); Common (≥1/100 to <1/10); Uncommon (≥1/1,000 to <1/100); Rare (≥1/10,000 to <1/1,000); Very rare (<1/10,000); Not known (cannot be estimated from the available data).
Adverse reactions reported are listed per system organ class, in decreasing order of seriousness. (See Table 4.)

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Abrysvo can be administered concomitantly with seasonal quadrivalent influenza vaccine (QIV, surface antigen, inactivated, adjuvanted). In a randomised study in adults 65 years of age and older, the criteria for non-inferiority of the immune responses in the co-administration versus the separate administration group were met. However, numerically lower RSV A and B neutralising titres and numerically lower influenza A and B haemagglutination inhibition titres were observed when Abrysvo and inactivated adjuvanted seasonal influenza vaccine were co-administered than when they were administered separately. The clinical relevance of this finding is unknown.
A minimum interval of two weeks is recommended between administration of Abrysvo and administration of a tetanus, diphtheria and acellular pertussis vaccine (Tdap). There were no safety concerns when Abrysvo was co-administered with Tdap in healthy non-pregnant women. Immune responses to RSV A, RSV B, diphtheria and tetanus on co-administration were non-inferior to those after separate administration. However, the immune responses to the pertussis components were lower on co-administration compared to separate administration and did not meet the criteria for non-inferiority. The clinical relevance of this finding is unknown.

Incompatibilities: In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
Special precautions for disposal and other handling: For use of vial of antigens for Abrysvo (powder), pre-filled syringe of solvent and vial adaptor: Abrysvo must be reconstituted prior to administration by adding the entire contents of the pre-filled syringe of solvent to the vial containing the powder using the vial adaptor.
The vaccine must be reconstituted only with the solvent provided.
Preparation for administration: Step 1. Attach vial adaptor: Peel off the top cover from the vial adaptor packaging and remove the flip off cap from the vial.
While keeping the vial adaptor in its packaging, centre over the vial's stopper and connect with a straight downward push. Do not push the vial adaptor in at an angle as it may result in leaking. Remove the packaging.
Step 2. Reconstitute the powder component (antigens) to form Abrysvo: For all syringe assembly steps, hold the syringe only by the Luer lock adaptor. This will prevent the Luer lock adaptor from detaching during use.
Twist to remove the syringe cap, then twist to connect the syringe to the vial adaptor. Stop turning when you feel resistance.
Inject the entire contents of the syringe into the vial. Hold the plunger rod down and gently swirl the vial until the powder is completely dissolved (approximately 1-2 minutes). Do not shake.
Step 3. Withdraw reconstituted vaccine: Invert the vial completely and slowly withdraw the entire contents into the syringe to ensure a 0.5 mL dose of Abrysvo.
Twist to disconnect the syringe from the vial adaptor.
Attach a sterile needle suitable for intramuscular injection.
The prepared vaccine is a clear and colourless solution. Visually inspect the vaccine for large particulate matter and discolouration prior to administration. Do not use if large particulate matter or discolouration is found.
Disposal: Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Store in a refrigerator (2°C-8°C).
Do not freeze. Discard if the carton has been frozen.
For storage conditions after reconstitution of the medicinal product, see Shelf life as follows.
Shelf life: 3 years.
The unopened vial is stable for 5 days when stored at temperatures from 8°C to 30°C. At the end of this period Abrysvo should be used or discarded. This information is used to guide healthcare professionals in case of temporary temperature excursions only.
After reconstitution: Abrysvo should be administered immediately after reconstitution or within 4 hours if stored between 15°C and 30°C. Do not freeze.
Chemical and physical in-use stability has been demonstrated for 4 hours between 15°C and 30°C. From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user.

Vaccines, Antisera & Immunologicals

J07BX05 - respiratory syncytial virus vaccines ; Belongs to the class of other viral vaccines. Used for active immunization against respiratory syncytial virus.

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