"Star Market Daily" June 5th News (Special reporter Xie Chen) Recently, the Food and Drug Administration (FDA) of the United States approved an mRNA respiratory syncytial virus (RSV) vaccine - mRESVIA (mRNA-1345), used to protect adults aged 60 and above from lower respiratory tract diseases caused by RSV infections (RSV-LRTD).

This is the third RSV vaccine globally, and also the world's first non-COVID mRNA vaccine developed by Moderna.

Despite the huge demand for RSV vaccines, the two RSV vaccines currently on the market, Arexvy and Abrysvo, have still not been able to meet the needs of high-risk groups - children and the elderly. What are the advantages of mRNA as an emerging vaccine technology? Will the approval of this vaccine disrupt the hundred billion dollar RSV blue ocean market?

▌RSV market rising, new vaccines entering the scene

Respiratory Syncytial Virus (RSV) is the most common pathogenic virus causing pneumonia. According to a study published in The Lancet in 2022, there were 33 million RSV infection cases globally in 2019, resulting in a large number of hospitalizations and deaths, especially affecting children under 5 years old and the elderly.

Prior to mRESVIA, two RSV vaccines had already been approved for marketing globally. In May 2023, the FDA approved the RSV vaccine Arexvy produced by GSK for use in people aged 60 and above. Another RSV vaccine, Abrysvo, produced by Pfizer, was also approved a few weeks later for the same age group.

In August 2023, the FDA approved pregnant women to receive one dose of Abrysvo during weeks 32 to 36 of pregnancy. Vaccination during this period can prevent respiratory diseases caused by RSV in infants for at least 6 months after birth.

According to the latest report from ResearchAndMarkets, the RSV market (including vaccines and therapeutic drugs) is expected to achieve a compound annual growth rate of 31.65% between 2024 and 2030, reaching $13.59 billion by 2030. Currently, the RSV vaccination rate for adults over 60 in the USA is only 11%.

Moderna's mRESVIA is the third RSV vaccine approved by the FDA for market. Compared to Abrysvo and Arexvy, both are recombinant protein vaccines, mRESVIA uses a more innovative mRNA technology.

After one year on the market, GSK's Arexvy and Pfizer's Abrysvo have achieved significant sales performance. According to the financial reports of the two companies, Arexvy's sales in the third quarter of 2023 reached 0.915 billion USD, and in the first quarter of 2024, the sales were 0.229 billion USD. Pfizer's Abrysvo had sales of 0.375 billion USD in the third quarter of 2023 and 0.1459 billion USD in the first quarter of 2024.

However, with the approval and market launch of the world's first mRNA RSV vaccine, it will undoubtedly have an impact on the existing market landscape. Due to the strong seasonality of RSV vaccine administration, the upcoming third quarter will be an important opportunity for the new vaccine to demonstrate its strength and market acceptance.

The median follow-up time of 3.7 months in the mid-term data shows that mRESVIA has a protective efficacy of 83.7% for patients with 2 or more RSV-LRTD symptoms, and 82.4% for patients with 3 or more symptoms.

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

Abrysvo has a protective efficacy of 67% and 86% for patients with 2 or more RSV-LRTD symptoms and 3 or more RSV-LRTD symptoms, respectively; Arexvy reduces the overall risk of RSV-LRTD by about 83%.

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

However, in long-term follow-up, mRESVIA's protective efficacy has shown a significant decline. Specifically, when the follow-up time extends to 8.6 months, its protective efficacy decreases to 62.5% for patients with 2 or more symptoms; for patients with 3 or more symptoms, the protective efficacy drops even further to 61.1%.

Compared to other vaccines, Pfizer's Abrysvo vaccine has demonstrated higher durability in protecting patients with 3 or more RSC-LRTD. Its protective efficacy reached 88.9% in the first epidemic season and remains at 77.8% in the second epidemic season. Similarly, GSK's Arexvy vaccine has shown strong protection for severe RSC-LRTD patients, reaching 94.1% in the first epidemic season and maintaining a high level of 78.8% after two epidemic seasons.

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

Some investors believe that the carefully designed antigen protection of recombinant protein vaccines is equivalent to mRNA, and with the addition of excellent adjuvants, the effect will be even better. Traditional technology routes are more favored in terms of safety and certainty. In the future, which technology route can better meet clinical needs will be a key evaluation point.

After COVID-19, mRNA vaccines are taking off again.

For decades, scientists and biomedical companies have been dedicated to researching and developing mRNA-based therapeutic methods and vaccines. It wasn't until the 21st century that significant breakthroughs were made in mRNA vaccine research as issues such as delivery and immunogenicity were gradually addressed.

Moderna is a leader in the field of mRNA vaccine development. The company has over 40 mRNA candidate vaccines in various stages of development targeting multiple 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 combo vaccine) have all progressed to late-stage development.

During an investor event held by Moderna in March this year, the company's management publicly announced the decision to advance three vaccines, mRNA-1189, mRNA-1468, and mRNA-1405, to critical late-stage development.

Moderna's first approved product is the mRNA COVID-19 vaccine (Spikevax), also the world's first approved mRNA vaccine. This vaccine received emergency use authorization during the COVID-19 pandemic and obtained formal approval from the FDA in 2022. mRESVIA is Moderna's second approved mRNA vaccine to be marketed following the COVID-19 vaccine.

Investors told the Science and Technology Innovation Board Daily reporter that Moderna company has received widespread attention in the past for its outstanding performance in the development of the COVID-19 vaccine. The mRNA technology used by the company shortens the vaccine development cycle, enabling rapid response to new pathogens. However, the previous doubts about Moderna mainly focused on whether its COVID-19 vaccine was widely used only out of urgent need rather than due to its technological level.

With the successful approval of Moderna's RSV vaccine, it proves that Moderna can not only develop the COVID-19 vaccine in a short time, but also continuously launch more types of vaccines using its mRNA technology platform. This achievement provides Moderna with a second growth curve, proving that they have a platform technology that can continuously introduce multiple vaccines, highlighting the broad value of Moderna's mRNA technology platform.

It is also because of the drive of the COVID-19 pandemic that the attention to mRNA technology has begun to increase. During this period, the domestic mRNA vaccine field has rapidly heated up, with many biotechnology companies such as walvax biotechnology, cansino biologics inc., and Sysmex MicroLife all involved in the development of this emerging field.

However, as the COVID-19 pandemic recedes, the market environment changes, and the attention to mRNA vaccines in the market begins to decrease. Now, the approval of the first non-COVID mRNA vaccine globally has become a new focus, whether it will reignite interest in this track, which has become the expectation of many.

The advantage of mRNA vaccines lies in the low cost and rapid development and production. Before the outbreak of seasonal epidemics such as RSV, researchers can pre-determine the prevalent strains, enabling large-scale, rapid, targeted production. In addition, when new pathogens appear, researchers can quickly design corresponding mRNA sequences and produce the corresponding vaccines. This rapid response capability makes mRNA vaccines significantly advantageous in responding to sudden epidemics.

"If new variants of the coronavirus appear again, at the current speed, (mRNA vaccines) can enter clinical trials within two weeks, and can be produced on a large scale at low cost." A researcher in the field of virology told reporters.

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

mRNA technology also holds the promise of personalized cancer treatment. In theory, it is possible to design mRNA vaccines targeting specific proteins of cancer cells, allowing human cells to produce these proteins, thus training the immune system to recognize and attack cancer cells with specific antigens.

Another investor interested in mRNA vaccine technology told reporters that the field of cancer treatment is highly competitive, and efficacy 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 technological routes.

However, some people still have concerns about the safety of mRNA vaccines, especially the mRNA vaccines for COVID-19. It has only been five years since the COVID-19 pandemic began, which is a very short period for vaccine evaluation. Continuous drug monitoring is needed to closely monitor the long-term effects and safety of the vaccine, said the source.