Respiratory syncytial virus (RSV) is one of the most frequently mentioned respiratory infectious diseases or pathogens in the winter of 2023.
Last November, at the press conference organized by National Health Commission, RSV was mentioned many times. On November 13, 2023, Wang Quan, chief physician of Beijing Children’s Hospital, said, "On the whole, virus is still the most common pathogen of respiratory tract infection in children, including influenza virus, rhinovirus, adenovirus and respiratory syncytial virus." On November 26, 2023, Mi Feng, spokesperson of the National Health and Wellness Commission and deputy director of the Propaganda Department, once pointed out that "monitoring shows that recently, respiratory infectious diseases are mainly influenza. In addition, rhinovirus, mycoplasma pneumoniae, respiratory syncytial virus, adenovirus, etc. "
RSV is a negative single-stranded RNA virus belonging to the genus Pneumonia of Paramyxoviridae. It is named because it is related to respiratory tract infection and can fuse infected cells. Moreover, RSV is the pathogen of acute respiratory infection after influenza.
According to a prospective surveillance study on all-age patients with acute respiratory infection in China from 2009 to 2019, the etiology and epidemiological characteristics of about 231,000 patients were analyzed. As a whole, influenza (28.5%), RSV(16.8%) and rhinovirus (16.7%) were the most common virus pathogens. Children and the elderly are the key people infected with RSV. Among them, in children under 5 years old, the positive rate of RSV detection exceeds that of influenza and rhinovirus, and RSV has become the most common virus pathogen that causes respiratory tract infection in children.
On January 2nd, AstraZeneca and Sanofi jointly announced that the long-acting monoclonal antibody Nirsevimab/Nisevimab was officially approved for marketing in National Medical Products Administration, China, to prevent lower respiratory tract infection (LRTI) caused by RSV in newborns and infants. This also fills the gap that there is no medicine for preventing RSV infection in infants in China.
It is worth noting that nisevimab is the first and only approved preventive measure to protect infants from RSV infection in China, covering healthy full-term infants, premature infants and infants susceptible to severe RSV infection due to special health conditions. In addition, nisevimab can achieve the effect of continuous protection for 5 months with one injection, that is, a typical RSV infection season (November-April in the northern hemisphere, totaling 5-6 months).
AstraZeneca and Sanofi revealed that nisevimab is expected to be listed in China during the RSV infection season in 2024-2025. Previously, nisevi monoclonal antibody had been approved in the European Union and the United States. The listing applications submitted by nisevimab in Japan and other markets are also under review.
At present, there are two main ways to prevent RSV infection: vaccination and drug prevention. In terms of drugs to prevent infection, infants can prevent RSV infection by injecting palizumab or nisevimab, while adults have no related RSV preventive drugs at present.
Both palizumab and nisevimab are products of AstraZeneca. Among them, palizumab is the first drug approved for the prevention of RSV infection in children in the world. It was approved for marketing in the United States in 1998 and has not been approved for marketing in China yet. The population covered by this drug is small, and the EU only recommends the use of this drug for premature infants within 6 months and under 35 weeks after birth, children with bronchopulmonary dysplasia (BPD) who need treatment in the past 6 months, and children with congenital heart disease (CHD) who are over 24 months old.
Moreover, compared with only one injection of nisevizumab in an RSV epidemic season, palizumab needs to be injected once a month in the RSV epidemic season, and the drug price is high.
In terms of vaccines, in 2023, the FDA approved the listing of RSV vaccines from Pfizer and GlaxoSmithKline. Infants within 6 months can take the initiative to inoculate Pfizer bivalent RSV vaccine Abysvo at 24-36 weeks of pregnancy to prevent RSV-related lower respiratory diseases, while people over 60 years old can be inoculated with GlaxoSmithKline’s RSV vaccine Arexvy or Pfizer bivalent RSV vaccine Abysvo for prevention, and there is no relevant RSV vaccine on the market for other age groups.
At present, GlaxoSmithKline’s RSV vaccine has been approved for clinical trials in China and has reached cooperation with domestic pharmaceutical companies. On June 19th, 2023, China National Medical Products Administration Drug Evaluation Center (CDE) official website announced that the RSV vaccine (AS01E adjuvant system) declared by GlaxoSmithKline had obtained implied permission for clinical trials and was suitable for active immunization to prevent lower respiratory diseases in adults aged 60 and above caused by RSV-A and RSV-B subtypes. On October 8, 2023, GlaxoSmithKline reached a strategic cooperation with Zhifei Bio, and Zhifei Bio won the priority agency right of RSV vaccine in mainland China.
It is worth mentioning that not long ago, the only RSV vaccine giant started a patent war. In August 2023, GlaxoSmithKline filed a patent lawsuit against Pfizer, claiming that Pfizer’s RSV vaccine Abrysvo infringed four patents of GlaxoSmithKline’s vaccine Arexvy. If GlaxoSmithKline wins the case, Pfizer will be permanently banned from selling and producing RSV vaccine in the United States in the future.
RSV is considered as the next field with a market of 10 billion dollars. Minsheng Securities Research Report shows that the overall global market size of RSV drugs (including preventive and therapeutic drugs) is expected to increase from $1.8 billion in 2020 to $12.8 billion in 2030, with a compound annual growth rate of 21.4%.
The market potential of RSV can be seen from the sales of products that have been listed. The aforementioned two RSV vaccines, Abrysvo of Pfizer and Arexvy of GlaxoSmithKline, achieved revenue of $375 million and $870 million respectively in the first quarter after being approved for marketing. Insight database shows that even palizumab, which has extremely limited coverage and short effect duration, has reached a sales peak of $1.6 billion in the past decade.
Many domestic pharmaceutical companies have also joined the development of the 10 billion blue ocean market. From the domestic research and development of RSV vaccine, many pharmaceutical companies, such as watson biological/Blue Magpie Bio, Unacon, Zhifei Bio, Clover Bio, Aidiweixin, participated in the research and development of RSV vaccine, but most of them are still in the early stage. Among them, the research and development progress of Aidiweixin is relatively fast, and its product ADV110 is in the second clinical stage; It is estimated that the phase II study will be extended from the elderly group to the infant group in 2024, aiming at protecting children aged 6 months to 5 years and the elderly over 65 years old.
According to the research of children’s RSV preventive drugs, TNM001 of Tylenol Mai Bo is in phase II/III clinical research, and RB0026 of Ruiyang Biotechnology is in phase I clinical trial. In addition to the products already on the market, the fastest research and development progress in the world is Clesrovimab of Merck, which has been in phase III clinical research.
Judging from the drugs under research for the treatment of children’s RSV infection, the domestic pharmaceutical company Aike Baifa AK0529 has submitted an application for NDA registration, and the progress is leading. AK0529 is an oral drug, which is suitable for children from birth to 24 months old. In addition, RV521 from Pfizer and EDP-938 from Enanta are under research all over the world, all of which are oral drugs, suitable for children aged from January to 36 months and 28 days to 36 months respectively. As of October 20, 2023, these two products are in phase II clinical trials.