mRESVIA
mRNA-1345
With its U.S. FDA approval in May 2024, mRESVIA® joined AREXVY and ABRYSVO, both featured in Drugs to Watch 2024, as respiratory syncytial virus (RSV) vaccines currently available for adults ages 60 years and older, helping further support the public health initiative to reduce the RSV-related disease burden. Even with available vaccines, RSV infections continue to be a public health concern, particularly for infants and older adults (65 years and older).
About mRESVIA®
- Moderna Inc
- mRNA sequence encoding a stabilized prefusion F glycoprotein
- Single-dose, 0.5-mL, intramuscular injection for active immunization to prevent lower respiratory tract disease (LRTD) caused by RSV in individuals ≥60 years old
- ~5m diagnosed RSV inpatient hospitalizations and outpatient events in the G7 markets in 2024
Why is it a drug to watch?
Using the same lipid nanoparticles (LNPs) as Moderna Inc’s COVID-19 vaccines, mRESVIA builds on the company’s foundational development of its mRNA platform. mRESVIA represents the first mRNA-based RSV vaccine, the first approval of an mRNA vaccine for a disease other than COVID-19 and the only RSV vaccine available in single-dose pre-filled syringes.
This vaccine further validates the clinical efficacy of vaccines based on the RSV F protein, which was a ground-breaking discovery that accelerated the recent development of vaccines against RSV, including AREXVY and ABRYSVO.
Approvals for mRESVIA are based on positive data from the global phase 3 clinical trial ConquerRSV:
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Participants included ~37,000 adults ages 60 years or older in 22 countries.
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Vaccine efficacy against RSV-related LRTD was 83.7% (95.88% CI 66.0%, 92.2%) over a median 3.7-month follow-up.
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In supplementary analysis of data from a median 8.6-month follow-up, sustained vaccine efficacy against RSV-related lower respiratory tract disease (LRTD) was:
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63.3% (95% CI: 48.7%, 73.7%) for two symptoms.
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74.6% (95% CI, 50.7, 86.9) for two or more symptoms, including shortness of breath.
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63.0% (95% CI, 37.3%, 78.2%) for three or more symptoms.
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The most commonly reported adverse events were injection site pain, fatigue, headache, myalgia and arthralgia.
The approval in the United States was followed by the CDC ACIP official recommendation for the use of the vaccine in adults 60 years of age and older.
Trials are ongoing to expand the population eligible for mRESVIA:
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Phase 3 study with high-risk individuals aged 18 years to <60 years (Part A) and individuals aged ≥18 years who received solid organ transplant (Part B)
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Single intramuscular injection (Part A)
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Two intramuscular injections on days 1 and 57 (Part B)
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Expected completion: July 2026
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Phase 2 study with children aged 2 years to <5 years (cohorts 1 and 3) and 5 years to 18 years at high risk of RSV (cohort 2)
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Single intramuscular injection (cohort 2) vs placebo (cohorts 1 and 3)
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Expected completion: April 2025
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Phase 2 study with individuals aged ≥18 years to <40 years who are pregnant and infants born to vaccinated mothers
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Single intramuscular injection in the period from 28 weeks to 36 weeks of gestation
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Expected completion: February 2026
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Phase 1 study with infants aged 5 months to <24 months
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Single intramuscular injection on days 1, 57 and 113
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Expected completion: July 2026
Review and approval status
August 2021
- Fast track designation: U.S. FDA
January 2023
- Breakthrough therapy designation: U.S. FDA
May 2024
- Approved: U.S. FDA
August 2024
- Approved: EMA
Actual and expected launch:
- 2024: European Union, United States
- 2025: Japan, United Kingdom
Patents estimated to expire beginning in 2038
Drug Timeline & Success Rates
Source: Cortellis Competitive Intelligence, Drug Timeline & Success Rates Prediction current as of October 31, 2024
How will mRESVIA impact the market for RSV prevention?
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The landscape looks likely to become increasingly crowded, with the RSV vaccine and prophylaxis market for the general vaccination population (adults 75 years and older and pregnant women to protect their babies through maternal immunization) potentially reaching $7bn by 2033 in the G7 countries.
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The two existing vaccines, ABRYSVO and AREXVY, identified as drugs to watch in the 2023 report, have fared very differently from each other.
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AREXVY was the first to enter the U.S., Canada, the E.U. and Japan and has since been approved in the E.U. and U.S. for at-risk individuals 50 years to 59 years old. 60% of adults in the U.S. aged ≥60 years who were vaccinated against RSV were vaccinated with AREXVY, contributing to the £1.238bn (1.65bn USD) total global sales in 2023. In fact, almost all of AREXVY’s 2023 sales were in the U.S.,2 and it currently leads in RSV vaccine market share, mostly due to its contracts with retail pharmacies. However, sales slowed in 2024, reaching only £432m ($555.7m) in the first three quarters of 2024, but this could change with the 2024-2025 RSV season.4
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ABRYSVO had the advantage of being launched with a broader population that includes both older adults (May 2023) and pregnant individuals (August 2023), and it was approved for high-risk adults aged 18 years to 59 years in October 2024 (the first to be approved for adults younger than 50 years). However, its sales only reached $890m after its launch in 2023, approximately the same amount AREXVY earned in Q3 2023 alone. Revenue was primarily from the older population in the U.S., although the company held hope for its impact on maternal immunization in 2024.5 Despite the population expansion, sales decreased to $356m in the first three quarters of 2024.6
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Other candidates in clinical development include the following:
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ADV-110 ( Advaccine Biopharmaceuticals): Recombinant protein vaccine for RSV
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BLB-201 (Blue Lake Biotechnology and CyanVac LLC): Recombinant viral vector vaccine for RSV
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CodaVax-RSV (Codagenix): cLive-attenuated viral vaccine for RSV
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D46/NS2/N/deltaM2-2-HindIll (NIAID): Recombinant viral vector vaccine for RSV
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DS-Cav1 (NIAID): Protein subunit vaccine for RSV
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IVX-A12 (Icosavax Inc/AstraZeneca): Virus-like particle and protein subunit vaccine for human metapneumovirus and RSV
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mRNA-1045 (Moderna Inc): mRNA vaccine for influenza and RSV
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mRNA-1230 (Moderna Inc): mRNA vaccine for SARS-CoV2, influenza and RSV
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mRNA-2365 (Moderna Inc): mRNA vaccine for RSV and human metapneumovirus (hMPV)
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MV-012-968 (Meissa Vaccines): Live-attenuated vaccine for RSV
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RSV 6120/deltaNS2/1030s (NIAID): cLive-attenuated viral vaccine for RSV
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RSV-276 (NIAID): Live-attenuated viral vaccine for RSV
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SP0125 (Sanofi): Live-attenuated viral vaccine for RSV
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V-306 (Virometix AG): Synthetic virus-like particle vaccine for RSV
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VN-0200 (Daiichi Sankyo): VAGA-9001a antigen; MABH-9002b adjuvant for RSV
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VXB-241 (Vicebio Ltd): Protein subunit vaccine using the company’s molecular clamp technology for human parainfluenza virus type 3 (PIV3), hMPV and RSV
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VXB-251 (Vicebio Ltd): Protein subunit vaccine using the company’s molecular clamp technology for hMPV and RSV
What gaps in treatment does mRESVIA fill?
Seasonal hospitalizations due to serious respiratory illness caused by RSV continue to be a public health issue, particularly for infants, young children, older adults and individuals with underlying health conditions such as COPD and asthma. The approvals of RSV vaccines address a significant need for infectious disease control, reduced morbidity and mortality, and decreased hospital burden, especially during the “tripledemic” of RSV, flu and COVID-19.
What hurdles might it need to overcome to reach blockbuster status?
As the third to market, mRESVIA will compete with ABRYSVO and AREXVY, and other RSV vaccines that are in late-stage development. Although mRESVIA has the advantage over the other RSV vaccines of not requiring preparation by health professionals, it has a shorter shelf-life and requires very cold storage temperatures to remain intact, which could limit where it is used. In addition, the CDC ACIP’s delay on a decision around recommending RSV vaccines for those aged 50-59 years in mid-2024 could hamper all RSV vaccine sales, in addition to the CDC’s suggestion that the vaccines are expected to confer multiple years of protection making it unnecessary to be vaccinated annually.
