The world's first! RSV prevention therapy for infants and young children was approved, and the tens of billions of market ushered in a competitive battle

Autumn and winter are coming, and respiratory infections are also troublesome.

According to the CDC, 1 in 500 babies under 6 months of age was hospitalized with respiratory syncytial virus (RSV) infection in the past month. Now, RSV has become the main reason for hospitalization of infants in the United States, and how to prevent RSV infection in infants and young children is a hot concern for many parents.

The good news is that RSV prophylaxis for a wide range of infant populations is finally here. On November 4, AstraZeneca/Sanofi jointly announced that its Beyfortus (nirsevimab) has been approved by the European Union for use in newborns and infants to help prevent RSV lower respiratory tract infections during the first respiratory syncytial virus (RSV) season.

64 million children infected every year!

The RSV market has huge potential

Respiratory syncytial virus (RSV) is a trans single-stranded RNA virus, infection with the virus often causes infant bronchiolitis, pneumonia and other respiratory diseases under 6 months of age, older children and adults can cause rhinitis, colds and other symptoms after infection, elderly RSV infection can lead to serious complications, such as chronic obstructive pulmonary disease and congestive heart failure.

According to statistics, RSV causes more than 360,000 hospitalizations and more than 24,000 deaths among adults worldwide every year. WHO data estimates that 64 million children worldwide are infected with RSV each year, of which 160,000 children die from RSV infection, which is an important cause of child death.

RSV is a recognized global health problem that brings a huge burden of disease to the world, prevention of RSV infection has been listed by WHO as one of the world's top priorities, and the research and development of RSV prevention products has also been listed by WHO as one of the highest priority products in the world.

However, there are limited global approvals for drugs/vaccines specifically for RSV prophylaxis. Prior to Beyfortus, only RI-002, RespiGam, and Synagis (Palivizumab) were approved for RSV prophylaxis.

Among them, RespiGam is an immunoglobulin containing high-titer RSV-neutralizing antibodies, RSV-IVIG, which was approved by the FDA in 1995 for RSV prevention in high-risk newborns under two years of age. However, due to the inconvenience of immunoglobulin preparation and use, RespiGam was later discontinued.

Synagis is a humanized murine monoclonal antibody that blocks the membrane fusion process by binding to RSV fusion proteins on the surface of the virus, and was approved by the FDA in June 1998 for the prevention of lower respiratory tract RSV infection in infants with bronchopulmonary dysplasia, premature infants, and children with congenital heart disease with hemodynamic abnormalities. According to the company's financial report, in 2008, Synagis entered the ranks of 1 billion US dollars, and its annual sales in the past ten years have changed between 9.00~1.425 billion US dollars. However, Synagis (palivizumab) is limited to high-risk infants and can only provide one month of protection and requires 5 injections to cover a typical RSV epidemic season.

Designed for babies and toddlers

RSV preventive antibody was approved for marketing

Beyfortus is a long-acting monoclonal antibody jointly developed by Sanofi and AstraZeneca, designed for all infants. Unlike active immune mechanisms (vaccines), which require activation of the body's immune system, monoclonal antibodies do not require activation of the immune system and provide timely, rapid, and immediate disease protection. As a result, Beyfortus became the world's first and only RSV prevention drug that can be widely used in newborns and infants, including healthy babies born at term or prematurely, or babies with special health conditions.

THE APPROVAL IS BASED ON A PHASE III MELODY STUDY CONDUCTED IN 21 COUNTRIES. This study assessed healthy late-term preterm and term infants (gestational age≥35 weeks) compared to placebo within 150 days of Beyfortus injection at the first RSV season. Results showed that Beyfortus reduced the rate of visits for RSV-associated acute lower respiratory tract infections such as bronchiolitis or pneumonia by 74.5% compared with placebo. As a means of RSV prevention designed for all infants, Beyfortus has had the same incidence of adverse effects as normal saline in multiple clinical trials.

Previously, Beyfortus was supported by the European Medicines Agency (EMA) Priority Drug Initiative (PRIME) and the US FDA granted "breakthrough therapy" designation. In China, niresevimab received implied approval for clinical trials in October 2020 and was included in the breakthrough therapy by CDE in January 2021.

RSV's 10 billion market opens a new round of competition

According to research data from China Insights Consulting, the overall global market size of RSV drugs is expected to grow from US$1.8 billion in 2020 to US$12.8 billion in 2030, with a compound annual growth rate of 21.4%. Among them, RSV drugs for children are expected to increase from $1.8 billion in 2020 to $11.7 billion in 2030, accounting for 91.1% of the global RSV drug market.

At present, more and more pharmaceutical companies have laid out the RSV market and developed a variety of products under research for RSV prevention or treatment, as shown in the table below.

Globally, some RSV vaccines/drugs are under development

There are various types of RSV products under development, including vaccines, chemical drugs, monoclonal antibodies, and biological agents such as interferon, and different types of RSV vaccines are also different, including recombinant vaccines and mRNA vaccines. From the perspective of specific indications, different products target different groups of people. From the perspective of research and development, RSV products are about to enter the outbreak period, and at least 10 products have entered phase 3 clinical trials.

In terms of RSV preventive vaccines, the marketing application for GSK's bivalent RSV vaccine GSK3844766A (RSVPreF3 OA) for the elderly is under review in the European Union and the United States, where the marketing application in the United States has been granted priority review by the FDA with a PDUFA date of 3 May 2023. In addition, GSK has developed an RSV vaccine for maternal immunization, GSK3888550A. However, Pfizer's bivalent RSV vaccine PF-06928316 (RSVpreF) has progressed faster, and was granted breakthrough therapy designation by the FDA in March this year, which is expected to become the first RSV vaccine for maternal immunity.

In terms of RSV therapeutics, in addition to interferon preparations (such as XW001), most of them are RSV fusion protein inhibitors, such as AK0529, JNJ-53718678 and Sisunatovir. On November 9 this year, the official website of CDE showed that the marketing application of ikobaifa's zirisovir enteric-coated capsules (AK0529) was included in the priority review, which is suitable for the treatment of respiratory infections in children aged 2 years and younger caused by respiratory syncytial virus.

In addition, companies have developed non-RSV fusion protein inhibitor drugs, such as EDP-938. The drug works by interfering with viral nucleoproteins. Unfortunately, the phase IIb clinical study of the drug in adults with RSV failed in May, failing to meet the primary endpoint of reduced total symptom score (TSS) and the secondary endpoint of antiviral.

brief summary

The development of any drug/vaccine carries great risks, and RSV is no exception.

Over the past 60 years, many pharmaceutical companies such as Pfizer, Novavax, and GSK have suffered setbacks in the RSV field, and products such as Novavax's Resvax (recombinant nanoparticle vaccine), Regeneron's suptavumab (monoclonal antibody) and Alynlam's ALN-RSV01 (siRNA drug) have finally been terminated. However, with the approval of Beyfortus, RSV prevention/treatment will enter a new level. In the near future, a number of RSV products may be approved for marketing to benefit more patients.