Vaccine Information: Arexvy (Page 2 of 3)

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

All pregnancies have a risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

AREXVY is not approved for use in persons <60 years of age.

In a clinical study that enrolled pregnant individuals who received an investigational unadjuvanted RSV vaccine that contained the same RSVPreF3 antigen as AREXVY, an increase in preterm births was observed compared to pregnant individuals who received placebo (sucrose reconstituted with saline).

Data

In a randomized controlled clinical trial that enrolled pregnant individuals in a 2:1 ratio, 3,557 received an investigational unadjuvanted RSV vaccine that contained the same RSVPreF3 antigen as AREXVY and 1,771 received placebo (sucrose reconstituted with saline) at 24 to 34 weeks gestation. In the vaccine and placebo groups, 6.81% and 4.95% of preterm births were reported, respectively.

8.2 Lactation

Risk Summary

It is not known whether AREXVY is excreted in human milk. AREXVY is not approved for use in persons <60 years of age. No human or animal data are available to assess the effects of AREXVY on the breastfed infant or on milk production/excretion.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for AREXVY and any potential adverse effects on the breastfed child from AREXVY or from the underlying maternal condition. For preventive vaccines, the underlying maternal condition is susceptibility to disease prevented by the vaccine.

8.4 Pediatric Use

Evidence from an animal model strongly suggests that AREXVY would be unsafe in individuals younger than 2 years of age because of an increased risk of enhanced respiratory disease. Safety and effectiveness in individuals 2 years through 17 years of age have not been established.

8.5 Geriatric Use

AREXVY is approved for use in individuals 60 years of age and older. Of the total number of participants (N = 24,966) who received AREXVY or placebo in Study 1 (NCT04886596), 13,943 (55.8%) were 60 to 69 years of age, 8,978 (36.0%) were 70 to 79 years of age, and 2,045 (8.2%) were 80 years of age and older. [see Adverse Reactions (6.1), Clinical Studies (14.1)].

11 DESCRIPTION

AREXVY (Respiratory Syncytial Virus Vaccine, Adjuvanted) is a sterile suspension for intramuscular injection. The vaccine is supplied as a vial of lyophilized recombinant respiratory syncytial virus glycoprotein F stabilized in pre-fusion conformation (RSVPreF3) as the antigen component, which must be reconstituted at the time of use with the accompanying vial of AS01_E adjuvant as the adjuvant suspension component.

The RSVPreF3 antigen is expressed by culturing genetically engineered Chinese Hamster Ovary cells in media containing no antibiotics or animal-derived proteins. The RSVPreF3 protein is purified by several chromatographic and filtration steps, formulated with excipients, filled into vials, and lyophilized.

The AS01_E adjuvant is composed of 3‑O ‑desacyl‑4’‑monophosphoryl lipid A (MPL) from Salmonella minnesota and QS-21, a saponin purified from plant extract Quillaja saponaria Molina, combined in a liposomal formulation. The liposomes are composed of dioleoyl phosphatidylcholine (DOPC) and cholesterol in a phosphate-buffered saline solution containing disodium phosphate anhydrous, potassium dihydrogen phosphate, sodium chloride, and water for injection.

After reconstitution, each 0.5-mL dose is formulated to contain 120 mcg of the recombinant RSVPreF3 antigen, 25 mcg of MPL, and 25 mcg of QS-21. Each dose also contains 14.7 mg of Trehalose, 4.4 mg of sodium chloride, 0.83 mg of potassium dihydrogen phosphate, 0.26 mg of dipotassium phosphate, 0.18 mg of polysorbate 80, 0.15 mg of disodium phosphate anhydrous, 0.5 mg of DOPC, and 0.125 mg of cholesterol.

AREXVY contains no preservative. Each dose may also contain residual amounts of host cell proteins (≤2.0%) and DNA (≤0.80 ng/mg) from the manufacturing process.

The vial stoppers are not made with natural rubber latex.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

AREXVY induces an immune response against RSVpreF3 that protects against LRTD caused by RSV.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

AREXVY has not been evaluated for carcinogenic or mutagenic potential or for impairment of fertility.

14 CLINICAL STUDIES

14.1 Efficacy in Adults 60 Years of Age and Older

Efficacy of AREXVY against RSV-associated LRTD in adults 60 years of age and older was evaluated in Study 1 (NCT04886596), an ongoing, Phase 3, randomized, placebo‑controlled, observer-blind clinical study conducted in 17 countries from Northern and Southern Hemispheres. Participants are planned to be followed for up to 36 months.

The study excluded participants who were immunocompromised. Participants with pre-existing, chronic, stable disease such as diabetes, hypertension, or cardiac disease were allowed to participate in the study if considered by the investigator as medically stable at the time of vaccination.

The primary population for efficacy analysis (referred to as the modified exposed set, included adults 60 years of age and older receiving 1 dose of AREXVY or placebo and who did not report an RSV-confirmed acute respiratory illness [ARI] prior to Day 15 after vaccination) included 24,960 participants randomized equally to receive 1 dose of AREXVY (n = 12,466) or placebo (n = 12,494). At the time of the primary efficacy analysis, participants had been followed for the development of RSV-associated LRTD for up to 10 months (median of 6.7 months).

At the time of first efficacy analysis of the ongoing Study 1, 51.7% were female; 79.4% were White, 8.7% were Black, 7.6% were Asian, and 4.3% were of other racial/ethnic groups including American Indian or Alaska Native, Native Hawaiian or Other Pacific Islander; 5.5% were of Hispanic or Latino ethnicity. The median age of participants was 69.0 years.

At baseline, 39.3% of participants had at least one comorbidity of interest; 19.7% of participants had an underlying cardiorespiratory condition (chronic obstructive pulmonary disease, asthma, any chronic respiratory/pulmonary disease, or chronic heart failure) and 25.8% of participants had endocrine and metabolic conditions (diabetes, advanced liver or renal disease).

Efficacy against Respiratory Syncytial Virus-associated Lower Respiratory Tract Disease

The primary objective was to demonstrate the efficacy of AREXVY in the prevention of a first episode of confirmed RSV-A and/or B‑associated LRTD during the first season.

Confirmed RSV cases were determined by quantitative Reverse Transcription Polymerase Chain Reaction (qRT‑PCR) on a nasopharyngeal swab during all ARI episodes. Acute respiratory illness (ARI) was defined by the presence of at least 2 respiratory symptoms/signs for at least 24 hours (nasal congestion, sore throat, lower respiratory symptoms/signs, as described below), or at least 1 respiratory symptom/sign plus 1 systemic symptom/sign (fever or feverishness, fatigue, body aches, headache, decreased appetite) for at least 24 hours. LRTD was defined based on the following criteria: the participant must have experienced at least 2 lower respiratory symptoms/signs, including at least 1 lower respiratory sign for at least 24 hours, or experienced at least 3 lower respiratory symptoms for at least 24 hours. Lower respiratory symptoms included: new or increased sputum, new or increased cough, new or increased dyspnea (shortness of breath). Lower respiratory signs included: new or increased wheezing, crackles/rhonchi, respiratory rate ≥20 respirations/min, low or decreased oxygen saturation (O₂ saturation <95% or ≤90% if baseline is <95%), need for oxygen supplementation.

Compared with placebo, AREXVY significantly reduced the risk of developing RSV‑associated LRTD by 82.6% (96.95% CI [57.9, 94.1]) in participants 60 years of age and older, which met the pre-specified success criterion for the primary study objective (Table 2). The median duration of efficacy follow-up was 6.7 months.

Vaccine efficacy analyses by age subgroup and for participants with at least one comorbidity of interest are presented in Table 2.

The vaccine efficacy against RSV A-associated LRTD cases and RSV B-associated LRTD cases was 84.6% (95% CI [32.1, 98.3]) and 80.9% (95% CI [49.4, 94.3]), respectively.

Table 2. Efficacy Analysis: First Respiratory Syncytial Virus-associated Lower Respiratory Tract Disease Overall, by Age and Co-morbidity Subgroups in Study 1^a (Modified Exposed Set)

Two-sided exact CI for vaccine efficacy is derived based on Poisson model adjusted by age categories and regions. N = Number of participants included in each group. n = Number of participants having first occurrence of RSV-confirmed LRTD occurring from Day 15 post-vaccination. a Study 1: NCT04886596. b CI = Confidence Interval (96.95% for the overall ≥60 years and 95% for all subgroup analyses).
Subgroup	AREXVY			Placebo			% Efficacy (CI)b
	N	n	Incidence Rate per 1,000 Person-Years	N	n	Incidence Rate per 1,000 Person-Years
Overall (≥60 years)	12,466	7	1.0	12,494	40	5.8	82.6 (57.9, 94.1)
60 to 69 years	6,963	4	1.0	6,979	21	5.5	81.0 (43.6, 95.3)
70 to 79 years	4,487	1	0.4	4,487	16	6.5	93.8 (60.2, 99.9)
Participants with at least 1 comorbidity of interest	4,937	1	0.4	4,861	18	6.6	94.6 (65.9, 99.9)

Compared with placebo, AREXVY significantly reduced the risk of developing RSV‑associated LRTD by 84.4% (95% CI [46.9, 97.0]) in participants 70 years of age and older. The vaccine efficacy in the subgroup of participants 80 years of age and older (1,016 participants who received AREXVY versus 1,028 participants who received placebo) cannot be concluded due to the low number of total cases accrued (2 cases among participants who received AREXVY and 3 cases among participants who received placebo).

Efficacy Against Severe Respiratory Syncytial Virus-associated Lower Respiratory Tract Disease

In Study 1, a severe RSV-associated LRTD was defined as an RT-PCR confirmed RSV‑associated LRTD with at least 2 lower respiratory signs, or as an RT-PCR confirmed RSV‑associated LRTD episode preventing normal, everyday activities. One case of severe RSV‑associated LRTD in the group that received AREXVY and 17 cases in the group that received placebo were reported, amongst which 2 cases required supportive therapy. Compared with placebo, AREXVY significantly reduced the risk of developing severe RSV‑associated LRTD by 94.1% (95% CI [62.4, 99.9]) in participants 60 years of age and older.