On June 5th, Science and Technology Innovation Board Daily (special correspondent Xie Chen) reported that the US Food and Drug Administration (FDA) recently approved an mRNA respiratory syncytial virus (RSV) vaccine - mRESVIA (mRNA-1345), used to protect adults aged 60 and above from RSV-induced lower respiratory tract disease (RSV-LRTD).

This is the third RSV vaccine in the world and the first non-COVID mRNA vaccine, developed by Moderna.

Despite the huge demand for RSV vaccines, the two RSV vaccines Arexvy and Abrysvo already on the market have not been able to meet the needs of the high-risk population - children and the elderly. What are the advantages of mRNA as an emerging vaccine technology? Will the approval of this vaccine stir up the RSV blue ocean of tens of billions of dollars?

▌The RSV market is rising, and new vaccines are entering the arena.

Respiratory syncytial virus (RSV) is the most common virus causing pneumonia. According to a study published in The Lancet in 2022, there were 33 million RSV infection cases worldwide in 2019, leading to a large number of hospitalizations and deaths, especially among children under five years old and the elderly.

Before mRESVIA, two RSV vaccines had been approved and marketed worldwide. In May 2023, the FDA approved GlaxoSmithKline's RSV vaccine Arexvy for use in people aged 60 or older. Pfizer's other RSV vaccine, Abrysvo, was also approved a few weeks later and is also available for people aged 60 or older.

In August 2023, the FDA also approved a single injection of Abrysvo for pregnant women between 32 and 36 weeks of gestation. Vaccination during this period can prevent RSV-induced respiratory diseases for at least 6 months after the baby is born.

According to the latest report from ResearchAndMarkets, the RSV market (including vaccines and therapeutics) is expected to achieve a compound annual growth rate of 31.65% from 2024 to 2030, and the market will reach 13.59 billion by 2030. However, the RSV vaccine coverage rate among people aged 60 and above in the United States is still only 11%.

Moderna's mRESVIA is the third FDA-approved RSV vaccine on the market. Compared with Abrysvo and Arexvy, which are both recombinant protein vaccines, mRESVIA uses more innovative mRNA technology.

One year after its launch, GSK's Arexvy and Pfizer's Abrysvo have already achieved significant sales performance. According to the financial reports of the two companies, Arexvy achieved sales of 915 million US dollars in the third quarter of 2023, and sales reached 229 million US dollars in the first quarter of 2024. Pfizer's Abrysvo had sales of 375 million US dollars in the third quarter of 2023 and 145.9 million US dollars in the first quarter of 2024.

However, with the FDA's approval of the world's first mRNA RSV vaccine, it will undoubtedly have an impact on the current market structure. As RSV vaccine vaccination has strong seasonality, the upcoming third quarter is an important opportunity for new vaccines to demonstrate their strength and market acceptance.

Mid-term data with a median follow-up time of 3.7 months shows that mRESVIA has a protective efficacy of 83.7% for patients with two or more RSV-LRTD symptoms and 82.4% for patients with three or more symptoms.

For vaccine products, mRESVIA has a very competitive protective efficacy, but the data performance of Abrysvo and Arexvy is also not bad:

Abrysvo has a protective efficacy of 67% for patients with two or more RSV-LRTD symptoms and 86% for patients with three or more symptoms; Arexvy reduces the overall risk of RSV-LRTD by about 83%.

Due to different statistical calibers and populations, the protective efficacy of the three vaccines is not suitable for direct comparison, but the clinical trial data of each vaccine shows that they can effectively prevent severe respiratory diseases caused by respiratory syncytial virus.

However, in long-term follow-up, the protective efficacy of mRESVIA has decreased significantly. Specifically, when the follow-up time was extended to 8.6 months, the protective efficacy of patients with two or more symptoms decreased to 62.5%, and that of patients with three or more symptoms decreased to 61.1%.

In contrast, Pfizer's Abrysvo vaccine has shown higher durability in protecting patients with three or more RSC-LRTD cases, and its protective efficacy reached 88.9% in the first season of the epidemic and remained at a high level of 77.8% in the second season. Similarly, GSK's Arexvy vaccine had a high protective efficacy of 94.1% on severely ill RSC-LRTD patients in the first season of the epidemic, and maintained a high level of 78.8% after two seasons.

Interestingly, after Moderna released the news of mRESVIA's approval, the company's stock price did not rise as expected, but fell by 5.9%.

Some investors believe that the antigen protection designed by recombinant protein vaccines is equivalent to that of mRNA. If excellent adjuvants are added, the effect will be better. And traditional technology routes are more favored in terms of safety and determinacy. In the future, which technology route can better meet clinical needs will be the key to evaluation.

▌After COVID-19, mRNA vaccines are on the rise again.

For decades, scientists and biomedical companies have been committed to researching and developing mRNA-based treatments and vaccines. However, it was not until the 21st century that significant breakthroughs were made in the research of mRNA vaccines, as issues such as delivery and immunogenicity were gradually resolved.

Moderna is a leader in the mRNA vaccine field. The company has more than 40 mRNA candidate vaccines in different stages of development, targeting various indications, including cancer and rare diseases. mRNA-1647 (CMV vaccine), mRNA-1010 (flu vaccine), mRNA-4157 (personalized cancer vaccine), and mRNA-1083 (COVID-19 + flu combination vaccine) have all entered late-stage development.

At an investor event held by Moderna in March this year, company management publicly announced that it has decided to promote the development of three vaccines, mRNA-1189, mRNA-1468, and mRNA-1405, to the critical late-stage development phase.

Moderna's first approved product is the mRNA COVID-19 vaccine (Spikevax), which is also the world's first approved mRNA vaccine. The vaccine was granted emergency use authorization during the COVID-19 pandemic, and received formal FDA approval in 2022. mRESVIA is Moderna's second approved mRNA vaccine, following the COVID-19 vaccine.

According to an investor who spoke to the "Star Market Daily," Moderna has received widespread attention in the past because of its outstanding performance in COVID-19 vaccine research. The use of mRNA technology by the company has shortened the research and development cycle of vaccines, enabling rapid response to new pathogens. However, previous questions about Moderna mainly focused on whether its COVID-19 vaccine was widely used only due to the urgency of the pandemic, rather than its technological capabilities.

With the successful approval of Moderna's RSV vaccine, it has been proven that Moderna can not only develop a COVID-19 vaccine in a short period of time, but also continue to launch various types of vaccines using its mRNA technology platform. This achievement provides Moderna with a second growth curve and highlights the extensive value of its mRNA technology platform.

It is precisely because of the promotion of the COVID-19 pandemic that the attention to mRNA technology has begun to rise. During this period, the investment heat in the field of mRNA vaccines in China has also rapidly increased, and many biotech companies including Walvax Biotechnology, Cansino Biologics Inc., and Microcore Biotech have joined the research and development of this emerging field.

However, as the COVID-19 pandemic fades away, the market's attention to mRNA vaccines begins to decline. Now, the approval of the world's first non-COVID mRNA vaccine has become a new focus, and whether it will once again promote this field has become the expectation of many people.

The advantage of mRNA vaccines is low cost and rapid research and production. Before seasonal epidemics such as RSV outbreaks, researchers can predict the strains that will be prevalent, enabling large-scale, targeted production in a timely manner. In addition, when new pathogens emerge, researchers can rapidly design corresponding mRNA sequences and produce corresponding vaccines. This ability to respond quickly gives mRNA vaccines a significant advantage in responding to outbreaks.

"If a new variant of the coronavirus appears again, (mRNA vaccines) can enter clinical trials within two weeks at the current rate, and can be produced on a large scale at low cost," a virology researcher told reporters.

In addition, the production of mRNA vaccines does not require the use of live viruses or bacteria, avoiding the complexity and safety risks associated with these biological materials.

mRNA technology is also expected to achieve personalized cancer treatment. Theoretically, mRNA vaccines can be designed to target specific proteins unique to cancer cells, allowing human cells to produce these proteins and train the immune system to recognize and attack cancer cells with specific antigens.

Another investor focusing on mRNA vaccine technology told reporters that the field of cancer treatment is highly competitive, and effectiveness is always the most important concern for patients and doctors. However, in the field of infectious disease prevention, mRNA vaccine technology may have more obvious advantages compared to other technology routes.

However, some people still have concerns about the safety of mRNA vaccines, especially the COVID-19 mRNA vaccine. From the beginning of the COVID-19 pandemic to now, which is only five years for vaccines, it is a very short testing period, and drug vigilance needs to be continued to closely monitor the long-term effectiveness and safety of the vaccine." the person said.