AstraZeneca and Sanofi announced that their MELODY Phase III trial of nirsevimab hit the primary endpoint in medically attended lower respiratory tract infections (LRTI) caused by RSV in healthy late preterm and term infants.
Respiratory syncytial virus (RSV) infections cause about 80,000 hospitalizations in children and 500 deaths each year. AstraZeneca and Sanofi announced that their MELODY Phase III trial of nirsevimab hit the primary endpoint in medically attended lower respiratory tract infections (LRTI) caused by RSV in healthy late preterm and term infants. This moves the drug one step closer to becoming the first new RSV treatment in 23 years.
RSV is one of the most frequent causes of bronchiolitis and pneumonia in children less than a year old in the U.S. In 2015, about 30 million cases were leading to more than three million hospitalizations globally, with about 60,000 in-hospital deaths in children five years or younger.
Nirsevimab is a long-acting antibody designed to act as a passive immunization for the prevention of LRTI caused by RSV. They believe that nirsevimab might only require a single dose during a typical five-month RSV season because of the longer half-life.
The current standard of care is AstraZeneca’s Synagis, which is limited to high-risk infants and only offers protection for a single month. It can require five injections during a complete RSV season.
“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 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, and primary investigator of the MELODY 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.”
The primary endpoint analysis was run earlier than expected. Global public health activities related to controlling COVID-19 decreased the circulation of all respiratory viruses, including RSV. As a result, sufficient numbers of cases to evaluate nirsevimab’s ability to prevent RSV LRTI compared to placebo had been collected before the pandemic. The trial is still ongoing to gather additional safety data.
The drug has received breakthrough designation from The China Center for Drug Evaluation under the National Medical Products Administration, from the U.S. Food and Drug Administration (FDA), and the European Medicines Agency’s Priority Medicines (PRIME) program.
No specific data were announced except that the trial met the primary efficacy endpoint. The drug is also being evaluated in the MEDLEY Phase II/III trial to study the safety and tolerability of nirsevimab compared to Synagis in preterm babies and children with chronic lung disease (CLD) and congenital heart disease (CHD) entering their first and second RSV seasons. Data for MEDLEY is expected in the second half of this year, which is also earlier than expected.
Synagis, also an antibody, was first approved in the U.S. in 1998. AstraZeneca acquired its developer, MedImmune, in 2007. Swedish Orphan Biovitrum AB (Sobi) owns the rights to Synagis in the U.S. following an agreement in late 2018. Sanofi initiated a partnership with AstraZeneca for nirsevimab four years ago for a 50% stake, paying AstraZeneca €120 million upfront and €495 million in various milestones.
In MELODY, 3,000 healthy babies who were not eligible for Synagis received either nirsevimab or placebo. They were then followed for 150 days to determine the numbers of lower-respiratory tract infections that required medical attention showed up in both groups.
The data indicated a statistically significant decrease in those types of infections in the nirsevimab cohort. A secondary endpoint was RSV-related hospitalizations, although the companies did not report the results. However, in a different study released last year, the drug successfully decreases the more severe outcomes.
Sanofi indicated that today’s announcement was “very topline” and expected to present more detailed data at an upcoming medical conference.
“These ground-breaking results mark a major scientific advancement in our effort to provide protection against respiratory syncytial virus for all infants,” said Mene Pangalos, executive vice president, BioPharmaceuticals R&D for AstraZeneca. “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 immunization for the general infant population, and these data bring us one step closer to delivering nirsevimab to infants worldwide.”
