Nirsevimab MELODY phase III trial met primary endpoint of reducing lower respiratory tract infections due to RSV in healthy infants.- Sanofi-AstraZeneca

Positive topline results from the Phase III MELODY trial showed nirsevimab reduced lower respiratory tract infections (LRTI) requiring medical attention (inpatient or outpatient) due to respiratory syncytial virus (RSV) in healthy preterm and term infants. RSV is the most common cause of LRTI and the leading cause of hospitalizations in all infants. Nirsevimab reached its primary endpoint, achieving a statistically significant absolute reduction of LRTI caused by RSV in healthy preterm and term infants compared to placebo through a typical RSV season. No clinically meaningful differences in safety results between the nirsevimab and placebo groups were seen. The overall safety profile of nirsevimab in the trial remains consistent with previously reported results. Results will be presented at an upcoming scientific congress and are anticipated to form the basis of regulatory submissions. “Despite respiratory syncytial virus being the leading cause of pneumonia and bronchiolitis in the first year of life, there is no routine preventative option currently approved for all infants,” said Dr William Muller, Associate Professor, Pediatrics, Northwestern University Feinberg School of Medicine and Scientific Director, Clinical and Community Trials, Ann & Robert H. Lurie Children’s Hospital of Chicago, Illinois, US and primary investigator of the MELODY Phase III trial. “These exciting trial data demonstrate the potential for nirsevimab to change the prevention landscape not only by providing protection to a broad population of infants across the full respiratory syncytial virus season, but also by achieving this with a single dose.” Nirsevimab, being developed in partnership with AstraZeneca, is the first investigational extended half-life monoclonal antibody (mAb) aiming to protect all infants entering their first RSV season, when they are at highest risk for severe RSV disease. With nirsevimab, a protective antibody is administered directly to the infant with the goal of providing rapid protection. The MELODY Phase III trial for nirsevimab met its primary endpoint of a statistically significant reduction in the incidence of medically attended lower respiratory tract infections (LRTI) caused by respiratory syncytial virus (RSV) compared to placebo in healthy late preterm and term infants (35 weeks or more) during their first RSV season. Nirsevimab is a long-acting antibody, using AstraZeneca’s proprietary YTE technology, and being developed by AstraZeneca and Sanofi, with the potential to provide immunity directly to infants and offer immediate protection against RSV. It is the first potential immmunisation to show protection against RSV in the general infant population in a Phase III trial. Preliminary analysis of the safety profile for nirsevimab was consistent with previous trial data. No clinically meaningful differences in safety results between the nirsevimab and placebo groups have been seen. RSV is a very common, contagious pathogen that causes seasonal epidemics of LRTI, including bronchiolitis and pneumonia It is the leading cause of hospitalisations in infants worldwide. The evaluation of the primary efficacy endpoint in the MELODY trial was conducted earlier than anticipated. Global public health measures to control COVID-19 have reduced the circulation of all respiratory viruses, including RSV. Sufficient cases had been accrued prior to the pandemic to evaluate nirsevimab’s ability to prevent RSV LRTI versus placebo. The trial is ongoing to collect additional safety data. Results from the MELODY trial will be presented at a forthcoming medical meeting. Nirsevimab is also being evaluated in the MEDLEY Phase II/III trial which will assess the safety and tolerability of nirsevimab compared to Synagis (palivizumab) among preterm infants and children with chronic lung disease (CLD) and congenital heart disease (CHD) entering their first and second RSV seasons. The MEDLEY trial is also expected to read out earlier with first data anticipated in the second half of 2021. MELODY, MEDLEY and the Phase IIb trial will form the basis of AstraZeneca’s regulatory submissions planned for 2022.