Nirsevimab Phase III MELODY Trial Achieves Primary Endpoint, Significantly Reducing RSV-Related Lower Respiratory Tract Infections in Healthy Infants

April 26, 2021 News /BioValleyBIOON/ --AstraZeneca(AstraZeneca) recently announced the evaluation of respiratory syncytial virus (RSV)Monoclonal Antibody DrugsThe Phase 3 MELODY trial of nirsevimab met its primary endpoint: in healthy late-preterm and full-term infants (≥35 weeks) during their first RSV season, compared with placebo,A single intramuscular dose of nirsevimab resulted in a statistically significant reduction in the incidence of lower respiratory tract infections (LRTI) caused by RSV.. The preliminary analysis of the safety of nirsevimab is consistent with previous trial data. There were no clinically meaningful differences in safety outcomes between the nirsevimab group and the placebo group.

It is worth noting that,This is the first time that potential passive immunization has demonstrated protective effects against RSV in the general infant population in a Phase 3 trial.RSV is a highly common infectious pathogen that causes seasonal epidemics of lower respiratory tract infections (LRTI), including bronchiolitis and pneumonia. Globally, RSV is the leading cause of hospitalization in infants and young children, with the majority of hospitalizations occurring in healthy, full-term infants. Clearly, all infants require protection against RSV, and nirsevimab has the potential to become an important complement to routine prevention programs.

Nirsevimab is a monoclonal antibody against respiratory syncytial virus (RSV) with an extended half-life (mean 59.3 days)., leveraging AstraZeneca's proprietary technology and jointly developed by AstraZeneca and Sanofi,As a passive immunotherapy, it has the potential to directly provide immunity to infants and offer immediate protection against RSV.

Nirsevimab is the first potential passive immunotherapy for infants, proven to provide sustained protection throughout the RSV season with a single intramuscular injection. To date,Nirsevimab Granted Breakthrough Therapy Designation by Three Major Global Regulatory Agencies, including:ChinaBreakthrough Therapy Designation granted by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA),United StatesFDAGranted Breakthrough Therapy Designation,EuropePriority Medicines (PRIME) designation granted by the European Medicines Agency (EMA).

RSV - Respiratory Syncytial Virus

Dr. William Muller, Principal Investigator of the MELODY trial and Associate Professor of Pediatrics at Northwestern University’s Feinberg School of Medicine, stated: “Although RSV is the leading cause of pneumonia and bronchiolitis in infants during their first year of life, there are currently no routine preventive measures available for all infants. These exciting trial data demonstrate that nirsevimab can provide protection to a broad population of infants throughout the RSV season with a single dose, thereby transforming the prevention landscape.”

Mene Pangalos, Executive Vice President of BioPharmaceuticals R&D at AstraZeneca, stated: “These breakthrough results mark a significant scientific advancement in our efforts to provide all infants with protection against RSV. Nearly all infants are infected with this virus before the age of two, leading to nearly 30 million cases of acute lower respiratory tract infections globally each year. As the first passive immunization therapy for RSV targeting the general infant population, nirsevimab has the potential to deliver substantial public health benefits, and these data bring us one step closer to making nirsevimab available to infants worldwide.”

Jean-François Toussaint, Global Head of R&D at Sanofi Pasteur, stated, “RSV is the leading cause of hospitalization among all infants. In fact, most hospitalizations occur in healthy, full-term infants. It is clear that all infants require protection against this virus, and we hope that nirsevimab will become an important complement to routine immunization programs.”

Synagis, a marketed product for the prevention of RSV in infants and young children

The assessment of the primary efficacy endpoint in the MELODY trial was conducted earlier than anticipated. Global public health measures implemented to control COVID-19 reduced the transmission of all respiratory viruses, including RSV. Sufficient cases had already been accrued prior to the COVID-19 pandemic to evaluate the ability of nirsevimab versus placebo to prevent RSV-LRTI. The trial is ongoing to collect additional safety data. The results of the MELODY trial will be presented at an upcoming medicalMeetingpublished above.

Nirsevimab is also being evaluated in the Phase 2/3 MEDLEY trial, which compares the safety and tolerability of nirsevimab with Synagis (palivizumab) in preterm infants and children with chronic lung disease (CLD) and congenital heart disease (CHD) entering their first and second RSV seasons. Data from the MEDLEY trial are also expected to be released earlier than anticipated, with initial results slated for publication in the second half of 2021. Data from the MELODY and MEDLEY trials, along with those from a Phase IIb trial (NCT02878330), will form the basis of AstraZeneca’s planned marketing authorization application for nirsevimab in 2022.

Advantages of Nirsevimab Over the Marketed Drug Synagis

Respiratory syncytial virus (RSV) is a common contagious virus that infects the respiratory tract and is the leading cause of acute lower respiratory tract infections (LRTI), primarily bronchiolitis and pneumonia, in infants and young children. Data indicate that nearly all infants and young children experience at least one RSV infection before the age of two, with infants under six months of age being the most affected population. RSV is highly contagious and can be transmitted from person to person via respiratory droplets or direct contact. The RSV epidemic season occurs annually from autumn to the following spring, with a typical epidemic duration of five months.

The current anti-RSV antibody, Synagis (palivizumab), is limited to high-risk infants and provides only one month of protection, requiring five injections to cover a typical RSV season.

Nirsevimab is a long-acting monoclonal antibody against respiratory syncytial virus (RSV), developed as a passive immunotherapy to prevent lower respiratory tract infections (LRTI) caused by RSV. This product is intended for use in a broader population of infants than the current standard of care, including: infants experiencing their first RSV season, and infants with congenital heart disease or chronic lung disease who are entering their first and second RSV seasons.

Nirsevimab is a passive immunotherapy that directly provides antibodies to infants to help prevent RSV; passive immunity differs from active immunity, which activates the human immune system through vaccines to prevent or combat RSV infection. Passive immunity can provide immediate protection, whereas active immunity requires several weeks to develop protective effects.

In March 2017, AstraZeneca and Sanofi reached an agreement to develop and commercialize nirsevimab. Under the terms of the agreement, AstraZeneca leads all development activities and initial regulatory approvals, and retains manufacturing activities, while Sanofi leads commercialization activities. (Bioon.com)

Original Source: Nirsevimab MELODY Phase III Trial Met Primary Endpoint of Reducing RSV Lower Respiratory Tract Infections in Healthy Infants