AstraZeneca and Sanofi have jointly announced that the European Commission (EC) has approved Beyfortus (nirsevimab) as a single-dose passive immunotherapy for all newborns and infants to prevent RSV lower respiratory tract disease (LRTI) during their first respiratory syncytial virus (RSV) season. The approval marks the first regulatory approval worldwide.
The approval of Beyfortus marketing marks a milestone in RSV prevention. Beyfortus is the first single-dose prophylaxis approved for RSV, and is also the first and only RSV prophylaxis for a wide population of newborns and infants at term or preterm. RSV is a common and highly contagious seasonal virus, and almost all children get RSV before age 2.
Beyfortus is the first long-acting antibody used to provide RSV protection to a wide range of neonates and infants. The Beyfortus is a pioneering passive immunotherapy for infants, designed for all infants, with a single dose of intramuscular injection, and is able to provide continuous RSV disease prevention effects at all times from birth to the end of the first RSV season. Currently, Beyfortus is being developed to enable use for infants experiencing the first RSV season as well as for children at higher risk during the second RSV season.
The approval of the Beyfortus-based clinical development project includes phase MELODY 3 trials, phase MEDLEY 2 / 3 trials, and a phase 2b trial (NCT02878330). These trials confirm the safety and efficacy of Beyfortus in providing protection to all infants by single-dose administration during the RSV season.
Specifically, in the critical MELODY efficacy trial, Beyfortus reached the primary endpoint: on day 151 (a typical RSV season) reduced lower RSV (LRTI) by 74.5% (95%CI: 49.6,87.1; p <0.001) compared to placebo. In the phase MEDLEY 2 / 3 trial, Beyfortus also showed similar safety and tolerability to Synagis (palivizumab), with a similar occurrence of emergency adverse events (TEAE) and serious adverse events (TESAE) between 2 treatment groups.
Iskra Reic, Executive Vice President of Vaccine and Immunotherapy at Astrazeneca, said: " Beyfortus is the first single-dose prophylaxis program for RSV approved in Europe, and also the first and only prophylactic program approved for a large infant population. Today's Beyforus marketing approval marks a major achievement in the scientific community that will address the ongoing global unmet medical needs for RSV prevention.”
RSV is a very common infectious agent that can cause a seasonal epidemic of LRTI (including bronchiolitis and pneumonia). Globally, RSV is the leading cause of hospitalization in infants and young children.
The active drug component of Beyfortus, nirsevimab, is a long-acting anti-RSV monoclonal antibody with an extended half-life and an average (± SD) of 59.3 days (± 9.6 days). Clinical data showed that on day 151,97.9% of infants had serum concentrations were 6.8 μg/mL above the target 90% effective concentration threshold after receiving single-dose injection; after 91 days, the mean nirsevimab serum concentration showed decay proportional to the concentration, without signs of nonlinearity.
The nirsevimab uses AstraZeneca's proprietary YTE technology, which is being developed jointly by AstraZeneca and Sanofi, as a passive immunotherapy that can provide immunity directly to all infants, providing immediate protection against RSV with single-dose intramuscular injections throughout the RSV season.
So far, nirsevimab has been awarded qualifications by various regulators worldwide to promote rapid development, including those granted by the China National Drug Evaluation Center (NMPA), the US FDA, the European Medical Products Agency (EMA) (PRIME), and the Japan Medical Research and Development Agency (AMED).
Respiratory syncytial virus (RSV) is a common infectious virus that infects the respiratory tract, and it is the primary pathogen of acute lower respiratory tract infections (LRTI, mainly bronchiolitis and pneumonia) in infants and young children. Data show that almost all infants have suffered from at least one RSV infection before the age of 2 years old, and infants under the age of 6 months are the main sick population. RSV is highly contagious and can be transmitted between humans through droplets or contact. The RSV season is from fall to spring, and the typical RSV season is 5 months.
The current anti-RSV antibody, Synagis (palivizumab), is limited to high-risk infants, provides only one month of protection, and requires five injections to cover a typical RSV epidemic season.
nirsevimab, an RSV mAb with an extended half-life, has been developed as a passive immunotherapy to prevent LRTI caused by RSV. The product was developed for a wider population of infants than the current standard of care, including: infants who will experience the first RSV epidemic season, congenital heart disease, or chronic lung disease infants who will enter the first and second RSV epidemic seasons.
nirsevimab is a passive immunotherapy that provides antibodies directly to infants to help prevent RSV, unlike active immunity, which activates the body's immune system to prevent or combat RSV infection. Passive immunity can provide immediate protection, while active immunity takes weeks to protect.
In March 2017, AstraZeneca and Sanofi reached a deal to develop and commercialize the nirsevimab. Under the terms of the agreement, Astrazeneca leads all development activities and preliminary regulatory approvals, and retains production activities, and Sanofi will lead commercial activities.
