The world's first! Infant RSV prevention therapy approved, tens of billions of market ushered in competition

The fall and winter season is coming, and with it comes the worry of respiratory infections.

In the past month, one in 500 infants under the age of 6 months were hospitalized for respiratory syncytial virus, or RSV, according to the CDC. Now, RSV has become the main cause of infant hospitalization in the United States, and how to prevent infant infection with RSV is a problem that many parents pay close attention to.

The good news is that RSV prophylactic drugs for a broad group of infants are finally here. Astrazeneca/Sanofi announced on 4 November that its Beyfortus (nirsevimab) has been approved in the European Union for use in newborns and infants to help prevent RSV lower respiratory tract infections as the first RSV epidemic season begins.

Respiratory syncytial virus (RSV) is a trans-single-stranded RNA virus. Infection with the virus often causes respiratory diseases such as bronchiolitis and pneumonia in infants under 6 months old, rhinitis and cold in older children and adults, and serious complications such as chronic obstructive pulmonary disease and congestive heart failure in the elderly.

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

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

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

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

Synagis is a humanized murine monoclonal antibody that blocks membrane fusion by binding to RSV fusion proteins on the surface of the virus. Synagis 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. Synagis hit the $1 billion mark in 2008, and its annual sales have ranged from $950 billion to $1.425 billion over the past decade, according to company reports. However, Synagis (palivizumab) is limited to high-risk infants and provides protection for only a month, requiring five injections to cover a typical RSV season.

Designed for infants and toddlers

RSV prophylactic antibody was approved for marketing

Beyfortus is a long-acting monoclonal antibody co-developed by Sanofi and Astrazeneca and designed for use in all infants. Unlike active immune mechanisms (vaccines), which need to activate the body's immune system, monoclonal antibodies do not need to activate the immune system and provide timely, rapid and direct disease protection. As a result, Beyfortus is the world's first and only RSV prophylaxis drug that is widely available for neonates and infants, including full-term or preterm healthy infants, or infants with special health conditions.

This approval is based on a Phase III MELODY study in 21 countries. The study evaluated Beyfortus versus placebo for 150 days after injection in healthy late preterm and term infants (gestational age ≥35 weeks) entering the first RSV epidemic season. The results showed that Beyfortus reduced the number of RSV-related acute lower respiratory tract infections (such as bronchiolitis or pneumonia) visits by 74.5% compared to placebo. Designed for the prevention of RSV in all infants, Beyfortus matched the rate of adverse reactions with saline in multiple clinical trials.

Beyfortus was previously supported by the European Medicines Agency's (EMA) Priority Medicines Programme (PRIME) and the US FDA's "Breakthrough therapy" designation. In China, niresevimab received implied approval for clinical trials in October 2020 and was included as a breakthrough treatment by the CDE in January 2021.

RSV 10 billion market opens a new round of competition

According to the research data of JV Consulting, the overall global market size of RSV drugs is expected to grow from $1.8 billion in 2020 to $12.8 billion in 2030, with a compound annual growth rate of 21.4%. 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.

There are various types of RSV products under development, including vaccines, chemical agents, monoclonal antibodies and interferon and other biological agents, and different RSV vaccines have different types, including recombinant vaccines and mRNA vaccines. From the specific indications, different products for the specific population is also different. In terms of research and development, RSV products are about to enter the explosive period, with at least 10 products entering phase 3 clinical trials.

In terms of RSV preventive vaccines, the marketing application for GSK's bivalent RSV vaccine for the elderly, GSK3844766A (RSVPreF3 OA), is under review in the EU and the US, where the marketing application has been granted priority review by the FDA and has a PDUFA date of 3 May 2023. In addition, GSK has developed an RSV vaccine, GSK3888550A, for maternal immunization. But Pfizer's bivalent RSV vaccine, PF-06928316 (RSVpreF), is on track to become the first RSV vaccine for maternal immunization, having been granted breakthrough therapy designation by the FDA in March.

In terms of RSV treatment drugs, except 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, CDE's official website showed that the marketing application of Acobaibifa's Chilisovir enteric-encapsulated capsule (AK0529) was included in the proposed priority review, suitable for the treatment of respiratory tract infection caused by respiratory syncytial virus in children under 2 years old.

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