April 26, 2021: 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 immunisation 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.
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, said: “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.
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.”
Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said: “These ground-breaking results mark a major scientific advancement in our effort to provide protection against respiratory syncytial virus for all infants.
Nearly all children will contract the virus before age two, leading to nearly 30 million acute lower respiratory tract infections globally each year.
Nirsevimab has the potential to provide a significant public health benefit as the first respiratory syncytial virus immunisation for the general infant population, and these data bring us one step closer to delivering nirsevimab to infants worldwide.”
Jean-François Toussaint, Global Head of Research and Development, Sanofi Pasteur, said: “Respiratory syncytial virus is the leading cause of hospitalisations in all infants. In fact, most hospitalisations occur in otherwise healthy infants born at term.
It’s clear all infants need protection from this virus, and we hope nirsevimab becomes an important addition to routine immunisation schedules.”
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.
Nirsevimab has been granted a breakthrough designation by three major regulatory agencies around the world.
These include Breakthrough Therapy Designation by The China Center for Drug Evaluation under the National Medical Products Administration; Breakthrough Therapy Designation from the US FDA; and access granted to the European Medicines Agency PRIority MEdicines (PRIME) scheme.
RSV is a common, contagious virus that infects the respiratory tract causing millions of hospitalizations globally, and is the most common cause of bronchiolitis and pneumonia in children younger than one year in the US.
Globally, in 2015, there were approximately 30 million cases of acute lower respiratory infections leading to more than three million hospitalizations, and it was estimated that there were 60,000 in-hospital deaths of children younger than five years.
Most hospitalization for RSV occur in otherwise healthy infants born at term.
Medically-attended LRTIs are associated with increased costs to the healthcare system.
MELODY is a randomised, placebo-controlled Phase III trial conducted across at least 21 countries designed to determine the incidence of medically attended LRTI due to RSV confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) testing through 150 days after dosing, versus placebo, in healthy infants entering their first RSV season.
Healthy late preterm and term infants born at 35 weeks 0 days or greater gestational age were randomised (2:1) to receive a single 50mg (in infants weighing <5kg) or 100mg (in infants weighing >5kg) intramuscular injection of nirsevimab or placebo.
Between July 2019 and February 2021 approximately 1,500 infants were dosed with either nirsevimab or placebo at the RSV season start.
An additional 1,500 infants will be enrolled in the Northern and Southern Hemispheres to complete the safety evaluation.
Nirsevimab is a long-acting antibody being developed as a passive immunisation for the prevention of LRTI caused by RSV.
It is being developed for use in a broader infant population than the current standard of care, Synagis, including for use in all infants experiencing their first RSV season and for infants with CHD or CLD entering their first and second RSV season.
Due to its extended half-life technology, nirsevimab may only require one dose during a typical five-month RSV season.
The current anti-RSV antibody, AstraZeneca’s Synagis, is limited to high-risk infants and provides one month of protection, requiring five injections to cover an RSV season.
Nirsevimab is a passive immunization, designed to provide RSV protection to all infants, whereby an antibody is given directly to an infant to help prevent RSV, unlike active immunization, where a person’s immune system is activated to prevent or fight infection through a vaccine.
Passive immunization could offer immediate protection unlike active immunization, which can take weeks to develop protection.