Nirsevimab Demonstrates Safety and Tolerability Comparable to Synagis in Phase 2/3 MEDLEY Trial for RSV Prevention in High-Risk Infants

RSV-Respiratory Syncytial Virus

June 28, 2021 /BioonBIOON/ --AstraZeneca(AstraZeneca) and Sanofi (Sanofi) recently announced respiratory syncytial virus (RSV)`Monoclonal antibody drugs`Positive topline results from the Phase 2/3 MEDLEY trial of nirsevimab. The trial was conducted in infants with chronic lung disease (CLD) or congenital heart disease (CHD) and/or born prematurely, a population at high risk for RSV entering their first RSV season. The trial evaluated the safety and tolerability of nirsevimab compared with the marketed drug Synagis (palivizumab). Results showed that,Nirsevimab demonstrated safety and tolerability similar to Synagis, with comparable incidence rates of treatment-emergent adverse events (TEAEs) or treatment-emergent serious adverse events (TESAEs) between the two groups.All results from the MEDLEY trial will be presented at the upcoming medicalMeetingpublished on. The trial is ongoing to collect additional safety data. Notably, MEDLEY is the third keyClinical Trials。

Nirsevimab is a long-acting anti-RSV monoclonal antibody with an extended half-life (mean 59.3 days) that utilizes AstraZeneca's proprietary YTE technology and is being co-developed by AstraZeneca and Sanofi,As a passive immunotherapy, it has the potential to directly provide immunity to all infants, delivering immediate protection against RSV throughout the entire RSV season via a single intramuscular injection.

RSV is a highly prevalent infectious pathogen that can cause seasonal epidemics of LRTI (including bronchiolitis and pneumonia). Globally, RSV is the leading cause of hospitalization among infants and young children.

Nirsevimab is the first potential passive immunization therapy for infants, demonstrated to provide sustained protection throughout the RSV season following a single intramuscular injection.To date, nirsevimab has been granted Breakthrough Therapy designation by three major global regulatory authorities, including:Breakthrough Therapy Designation granted by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA), United StatesFDABreakthrough Therapy Designation granted by, and Priority Medicines (PRIME) designation granted by the European Medicines Agency (EMA).

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

Currently, nirsevimab is also being evaluated in the Phase 3 MELODY trial, which met its primary endpoint: during the first RSV season in healthy late preterm and term infants (≥35 weeks gestational age),Compared with placebo, a single intramuscular dose of nirsevimab resulted in a statistically significant reduction in the incidence of lower respiratory tract infection (LRTI) associated with respiratory syncytial virus (RSV).. Preliminary analysis of nirsevimab safety is consistent with previous trial data. There were no clinically meaningful differences in safety outcomes between the nirsevimab group and the placebo group. Data from the MEDLEY, MELODY, and a Phase IIb trial (NCT02878330) will form the basis for AstraZeneca’s planned submission of a marketing authorization application for nirsevimab in 2022.

Principal Investigator of the MEDLEY Trial, Professor of Pediatrics and Microbiology at the State University of New YorkImmunologyProfessor Joseph Domachowske, M.D., stated: “These data are highly significant for nirsevimab, as they demonstrate a comparable safety and tolerability profile for nirsevimab versus the only currently available preventive treatment for lower respiratory tract infections caused by RSV in premature infants and infants with underlying health conditions. Given that a typical RSV season lasts nearly five months, offering a prophylactic option represents a potential advantage, as it can help protect all infants throughout the season with a single dose.”

Mene Pangalos, Executive Vice President of BioPharmaceuticals R&D at AstraZeneca, said: “RSV is the leading cause of infant hospitalization. These results, combined with recent positive efficacy results from the Phase 3 MELODY trial and data from the Phase 2b trial, provide substantial evidence of the potential for nirsevimab to protect all infants from RSV infection with a single dose. We look forward to sharing the results with regulatory authorities.”

Jean-François Toussaint, Head of Global R&D at Sanofi Pasteur, stated: “RSV is a major pediatric infectious disease for which no preventive measures are currently available for all infants. We believe nirsevimab has the potential to become an important and innovative routine immunization for all infants, including those born preterm or at term, whether healthy or with underlying health conditions.”

Advantages of Nirsevimab Over the Commercially Available 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 will have experienced at least one RSV infection by the age of 2, with infants under 6 months of age representing the primary affected population. RSV is highly contagious and can be transmitted between individuals via respiratory droplets or contact. The RSV season typically spans from autumn to the following spring, with a typical duration of 5 months.

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

Nirsevimab is an RSV monoclonal antibody with an extended half-life, developed as a passive immunotherapy to prevent lower respiratory tract infection (LRTI) caused by RSV. The product is intended for a broader infant population than the current standard of care, including: infants entering their first RSV season, and infants with congenital heart disease or chronic lung disease who will enter their first and second RSV seasons.

Nirsevimab is a passive immunization therapy that directly provides antibodies to infants to help prevent RSV. Passive immunization differs from active immunization, which activates the human immune system through vaccination to prevent or combat RSV infection. Passive immunization provides immediate protection, whereas active immunization requires several weeks to develop a protective effect.

In March 2017, AstraZeneca and Sanofi reached an agreement for the development and commercialization of nirsevimab. Under the terms of the agreement, AstraZeneca will lead all development activities and initial regulatory approvals, and retain manufacturing activities, while Sanofi will lead commercialization activities. (Bioon.com)

Original Source:Nirsevimab shows positive topline results in RSV Phase 2/3 MEDLEY trial