Moderna's RSV Vaccine, mRESVIA, Receives FDA Approval for Expanded Use in Adults Aged 18-59
Moderna announced that the U.S. Food and Drug Administration (FDA) has approved mRESVIA (mRNA-1345), its respiratory syncytial virus (RSV) vaccine, fo...
Breakthrough Clinical Results
Moderna announced that the U.S. Food and Drug Administration (FDA) has approved mRESVIA (mRNA-1345), its respiratory syncytial virus (RSV) vaccine, for adults aged 18-59 years at increased risk for RSV disease. This expands the previous approval for adults 60 and older. The approval is based on a Phase 3 study (NCT06067230) demonstrating the vaccine's safety and immunogenicity in this younger adult population with underlying health conditions. The vaccine was generally well-tolerated, with common side effects including injection site pain, fatigue, headache, muscle pain, and joint pain. Moderna plans to make mRESVIA available for both younger and older adults for the 2025-2026 respiratory virus season.
Key Highlights
- FDA approves Moderna's mRESVIA RSV vaccine for adults aged 18-59 at increased risk for RSV disease.
- Approval expands the existing indication for adults aged 60 and older.
- Phase 3 trial (NCT06067230) demonstrated safety and immunogenicity in the 18-59 age group.
- mRESVIA will be available for both younger and older adults during the 2025-2026 respiratory virus season.
Incidence and Prevalence
Global RSV Burden:
Estimating the precise global incidence and prevalence of RSV infection is challenging due to variations in study methodologies, surveillance strategies, and reporting practices across different regions. Many studies focus on specific populations (e.g., hospitalized children, older adults) or geographic areas, making it difficult to generalize findings to the entire global population. Additionally, RSV incidence can fluctuate significantly from year to year, influenced by factors like climate and public health interventions.
Children:
- Incidence of RSV-associated acute lower respiratory infection (ALRI): A 2005 estimate indicated 33.8 million new episodes of RSV-ALRI globally in children under 5 years, representing 22% of all ALRI episodes. Of these, at least 3.4 million were severe cases requiring hospitalization. Nearly all RSV-ALRI deaths occurred in developing countries.
- Hospitalization rates: A more recent analysis (2019) estimated a median of 8.25 thousand annual RSV-ALRI hospitalizations per country in children under 5, with a median rate of 514 hospitalizations per 1000 children. The majority of these hospitalizations occurred in infants under 1 year old.
- Mortality: In 2005, between 66,000 and 199,000 children under 5 died from RSV-ALRI, with 99% of these deaths occurring in developing countries. A 2021 study estimated 502,000 deaths in children younger than 5 years from lower respiratory infections (including RSV), with 254,000 of these deaths occurring in low Socio-demographic Index countries.
Adults:
- Incidence: Data on adult RSV incidence are more limited. A 2022 literature review found highly variable RSV incidence estimates in adults, with higher rates in older adults and those with underlying conditions. Hospital-based studies are more common than population-based studies, potentially overestimating the true community incidence.
- Hospitalization: A US study estimated annual RSV hospitalization rates of 178 per 100,000 adults aged 65 and older based on nasal/NP swab PCR testing alone. Adjusting for the increased diagnostic yield of paired serology or sputum testing, the estimated rate increased to 267 hospitalizations per 100,000. Another US study found a high burden of RSV hospitalization, with annual incidence ranging from 44.2 to 58.9 per 100,000 adults overall and even higher rates in older adults and those with comorbidities like COPD, coronary artery disease, and congestive heart failure.
- Mortality: A US study analyzing death certificate data from 2005-2016 found an increase in RSV-associated deaths, particularly among older adults, primarily due to RSV pneumonia. However, the study acknowledged that death certificate data likely underestimate the true RSV mortality burden.
Overall:
RSV remains a significant global health concern, particularly for young children and older adults. More research, particularly population-based studies with standardized methodologies, is needed to improve the accuracy and comparability of RSV burden estimates across different populations and geographic regions. This information is crucial for informing public health interventions, resource allocation, and the development and implementation of effective prevention strategies, such as vaccination.
Risk Factors and Comorbidities
Respiratory syncytial virus (RSV) is a common respiratory virus that causes mild, cold-like symptoms in most people. However, it can lead to serious complications, especially in infants, young children, and older adults. Several risk factors and comorbidities increase the likelihood of developing severe RSV disease or requiring hospitalization.
Here are the top 3 risk factors and comorbidities for the occurrence of RSV disease, based on the provided medical literature:
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Young Age (Infants <6 months):
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Infants, particularly those younger than 6 months, are at the highest risk of severe RSV disease. This is due to their underdeveloped immune systems and smaller airways, which can become easily obstructed. Multiple studies highlight the increased risk in this age group, with some reporting the highest incidence rates of RSV-associated lower respiratory tract infection (LRTI) in infants aged 3-5 months. Infants aged 0-5 months also have a significantly higher odds ratio (OR) of being diagnosed with RSV and requiring ICU admission. Additionally, young age is a predictor of the need for respiratory support during RSV hospitalization in children with heart disease.
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Prematurity:
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Preterm infants are at significantly increased risk of RSV hospitalization and severe disease. This is because their lungs are not fully developed, making them more susceptible to respiratory infections. Studies have shown higher RSV hospitalization rates in preterm infants compared to term infants, with the highest rates in the lowest gestational age infants. Prematurity is also a risk factor for ICU admission in RSV cases and is associated with severe RSV disease in hospitalized children. Preterm birth, especially with chronic lung disease, further increases the risk of severe RSV infection.
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Underlying Chronic Medical Conditions:
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Children and adults with underlying chronic medical conditions are at increased risk of severe RSV disease and complications. These conditions can include:
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Chronic lung disease (CLD): CLD, including bronchopulmonary dysplasia (BPD), increases the risk of hospitalization and severe outcomes in RSV-infected children. It is also a predictor of PICU admission.
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Congenital heart disease (CHD): CHD is a significant risk factor for RSV hospitalization and severe disease, particularly in infants. It is also an independent predictor of fatality due to RSV among preterm infants.
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Neuromuscular disorders: These disorders increase the risk of worse clinical outcomes in older children hospitalized with RSV.
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Immunocompromised states: Individuals with weakened immune systems, such as those with HIV or undergoing organ transplantation, are at higher risk of severe RSV infection and complications.
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Down syndrome: Down syndrome is significantly associated with death in severe RSV infections and increases the risk of RSV-associated LRTI requiring hospitalization.
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Other chronic conditions: Other chronic conditions, such as cardiovascular disease, neurological disorders, blood disease, liver disease, and chronic kidney disease, also contribute to the risk of severe RSV disease and ICU admission.
It's important to note that while these are the top 3 risk factors and comorbidities, other factors can also play a role in RSV disease severity. These include environmental factors like exposure to tobacco smoke, household crowding, and daycare attendance, as well as host factors like male sex, low birth weight, and family history of atopy or asthma.
Drug used in other indications
The provided text focuses on trials involving mRNA-1345 (mRESVIA) for RSV in combination with other vaccines, specifically influenza and SARS-CoV-2. It doesn't mention trials for other indications besides RSV.
Specifically, a phase 3 trial evaluated coadministration of mRNA-1345 with:
- A standard-dose quadrivalent inactivated influenza vaccine (SIIV4)
- A bivalent SARS-CoV-2 mRNA-1273.214 vaccine (Wuhan-Hu-1 plus omicron BA.1)
The trials aimed to assess the safety and immunogenicity of these combinations compared to individual vaccines. The results indicated acceptable safety profiles and mostly non-inferior immune responses for the coadministered vaccines. However, the seroresponse rate difference in neutralizing antibodies against RSV-A when coadministered with SIIV4 did not meet the non-inferiority criterion.
Other texts mention mRNA-1345 being tested in phase 3 clinical trials for RSV in infant or elderly populations, and Moderna receiving FDA fast-track designation for mRNA-1345 against RSV in adults over 60. One text also mentions a phase 1 dose-ranging study evaluating mRNA-1345 in adults aged 65-79, which found it well-tolerated and immunogenic after a single injection and a 12-month booster.
None of the provided texts discuss trials of mRNA-1345 for indications other than RSV.
