According tο a recent systematic analysis focusing on children younger than five years old, there were globally estimated 33 million RSV-associated acute lower respiratory infection episodes (ALRTI) in 2019, 3.6 million RSV-associated ALRTI hospital admissions, 26,300 RSV-associated ALRTI in-hospital deaths, and 101,400 RSV-attributable overall deaths in children up to 5 years of age. In infants aged 0-6 months, there were estimated 6.6 million RSV-associated ALRTI episodes.
In the same analysis it is mentioned that 95% or more of RSV-associated ALRTI episodes and 97% or more of “RSV-attributable deaths across all ages were in low-income and middle-income countries (LMICs)”.
The numbers above prove the RSV burden for vulnerable populations, making an RSV vaccine a need of the hour.
What is RSV and why we need RSV vaccines.
Respiratory syncytial virus (RSV) is a communicable disease that causes infection of the lungs and respiratory tract. Its incubation period is 4 to 6 days, and an infected person can transmit the virus for 3 to 8 days by its droplets.
Usually, RSV causes a mild infection presenting with flu-like symptoms such as cough, wheezing, sneezing, sore throat and congested or runny nose.
However, vulnerable populations such as young children with small-diameter airways (the risk is highest for one month old newborns and gradually decreases afterward), and geriatrics with pulmonary disease (especially COPD) are at highest risk for severe infection and the ones who will benefit the most from a vaccine.
This article presents an overview of all RSV associated vaccines, and indications about the eligible for vaccination populations with each one of them.
The RSV vaccine landscape
The quest for the RSV vaccine began forty years ago. The first RSV vaccine, FI-RSV vaccine trial, failed because the antibodies produced were not potent enough to neutralize the virus. This in turn has led to rigorous research for successful vaccination.
BEYFORTUS developed by AstraZeneca and Sanofi, AREXVY by GSK, and ABRYSVO by Pfizer are approved by the US FDA and EMA. Launch expected by the 2023-2024 RSV season. mRNA-1345 is currently in the preregistration stage.
The efficacy, safety, and regulatory status of each product is compared at the table below:
Apple-to-apple comparison of various RSV vaccines
| Vaccine | BEYFORTUS (Nirsevimab) | AREXVY (RSVPreF3) | ABRYSVO (RSVpreF) | mRNA-1345 |
| Company | AZ/ Sanofi | GSK | Pfizer | Moderna |
| Patient segment | Healthy late-preterm and term infants | Older adults | Infants through maternal immunization and older adults | Older adults |
| Efficacy | Interim data: the statistical success criterion was not met for the second primary endpoint though clinically meaningful efficacy was observed | Demonstrated vaccine efficacy of 83.7% against RSV-LRTD as defined by two or more symptoms, and a VE of 82.4% against RSV-LRTD defined by three or more symptoms | ||
| Reduction the incidence of MA-LRTI | 74.5% (95% CI 49.6, 87.1; p<0.001) vs. placebo through day 151 (a typical RSV season) with a single dose | Single dose demonstrated 67.2% (97.5%CI, 48.2-80.0) reduction in RSV-LRTD, including subjects with co-morbidities | 57.1% (CI: 14.7%, 79.8%) through the first 90 days of life; 51.3% (CI: 29.4%, 66.8%) through 6-month follow-up | |
| Reduction the incidence of severe MA-LRTI | 94.1% (95% CI, 62.4–99.9; p<0.0001) | 81.8% (CI: 40.6%, 96.3%) through the first 90 days of life; 69.4% (CI: 44.3%, 84.1%) through 6-month follow-up | ||
| Safety | Favorable safety profile | RSVpreF was well-tolerated with no safety concerns; local and systemic events mostly mild to moderate and short lived | Generally well-tolerated, with no safety concerns | |
| AE | BEYFORTUS: 87.4% vs placebo: 86.8 % | Injection site pain, fatigue, headache, myalgia, and arthralgia. | ||
| Grade 3 or higher AE | BEYFORTUS: 3.6% vs placebo: 4.3% | Systemic: mRNA-1345: 4.0%; placebo: 2.8%
Local: mRNA-134: 5 3.2%; placebo: 1.7% |
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| SAE | BEYFORTUS: 6.8% vs placebo: 7.3% | |||
| RWE study | 83.21% (95% CI 67.77 to 92.04; P<0.001) reduction in hospitalizations due to RSV-related LRTD | |||
| Regulatory status | The US FDA has approved BEYFORTUS in Jul 2023.
Approved in the EU in Nov 2022 Regulatory applications are under review in China, Japan and other countries |
The US FDA approved AREXVY in May 2023.
Regulatory submission accepted by Japanese regulator in Oct 2022 |
Approved for older adults by the US FDA in May 2023 and for infants through active immunization of pregnant individuals in Aug 2023.
In review with Japan’s MHLW since Feb 2023. Received EU EMA approval for older adults and for infants in Aug 2023 In review with Canada since Apr 2023 |
Rolling BLA submission to the US FDA in Jul 2023. Has BTD and FTD designation from the US FDA.
Filed for MAA with EMA and Australia (Priority Pathway). Global submissions on the way |
| Expected launch | 2023-2024 RSV season in the US | Launch planned on time for 2023/2024 in the US and EU.
H2 2023 launch in JP. |
Launched for adults (60+); RSV infant (through maternal immunisation) launch expected in H2 2023 |
Table 1: Apple-to-apple comparison of various RSV vaccines
BEYFORTUS immunizes newborns and infants; while AREXVY immunizes geriatric patients; and ABRYSVO immunizes both infants and geriatrics.
Another distinguishing feature of ABRYSVO is that it is a maternal vaccine which immunizes their infants while eliminating any risk of injection.
mRNA-1345 is currently being evaluated in pediatric populations.
Regulatory agencies on RSV vaccines.
As stated at Sanofi press release the US FDA Advisory Committee has recommended BEYFORTUS (nirsevimab) “as the first immunization against RSV disease for all infants”.
AREXVY (GSK) has received recommendations from the US CDC Advisory Committee on Immunization Practices “for the prevention of RSV disease in adults aged 60 and older” and is the first RSV vaccine EMA approved for older adults having gained positive recommendation from CHMP.
Following the recent approval of BEYFORTUS, the CDC Advisory Committee has unanimously recommended the routine use of BEYFORTUS.
Pharma is ready for the RSV 2023–2024 season.
Unlike the previous years, this year in the fall season, there will be three new RSV vaccines available in the market: BEYFORTUS, AREXVY, and ABRYSVO. These vaccines would potentially decrease the incidence of mortality as well as hospitalization. At the same time, they can also reduce healthcare costs.
Over the years to come, MSD’s Clesrovimab, Janssen’s VAC 18193, and Novavax’ RSV F Vaccine, which are currently being evaluated in Phase 3 studies, are expected to enter the market.
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The article was published on 24th August 2023 and includes all information available till this day, with Pfizer’s press release “European Commission Approves Pfizer’s ABRYSVO™ to Help Protect Infants through Maternal Immunization and Older Adults from RSV” being the most recent one.
Sources:
Press Release: FDA approves Beyfortus™ (nirsevimab-alip) to protect infants against RSV disease
RSV Vaccines Are Finally Here after Decades of False Starts – Scientific American.