Detailed results from the positive MELODY Phase III trial showed a single dose of AstraZeneca and Sanofi's nirsevimab met the primary efficacy endpoint reducing the incidence of medically attended lower respiratory tract infections (LRTI) caused by respiratory syncytial virus (RSV) by 74.5% (95% CI 49.6, 87.1; p1-2
The trial involved healthy term and late preterm (gestational age ≥35 weeks) infants entering their first RSV season.1-2
Additionally, the MEDLEY Phase II/III trial, which evaluated safety and pharmacokinetics of nirsevimab in infants with congenital heart disease (CHD), chronic lung disease (CLD) and prematurity entering their first RSV season, demonstrated nirsevimab had a similar safety and tolerability profile compared to Synagis (palivizumab).3-4
Serum levels of nirsevimab following dosing (on day 151) in this trial were comparable with those observed in the MELODY Phase III trial, indicating similar protection in this population to that in the healthy term and late preterm infants is likely.1-4Synagis is currently the only available preventative option for RSV.
Nirsevimab is an investigational long-acting antibody designed to protect all infants through their first RSV season with a single dose. It is the first potential immunisation to show protection against RSV in the general infant population in a Phase III trial.1-2
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: "We know that respiratory syncytial virus has seen a resurgence with the easing of COVID-19 public health measures. This shows us a broad immunization approach is needed to help mitigate the substantial global burden respiratory syncytial virus places on infants, their families and healthcare services. These exciting data show that nirsevimab has the potential to offer RSV protection for all infants, which would be a paradigm shift in the approach to this disease."
Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: "Respiratory syncytial virus is a leading cause of lower respiratory tract infections, such as bronchiolitis or pneumonia, as well as hospitalisations in infants. These data show for the first time, the potential to significantly protect all infants through their first respiratory syncytial virus season with a single dose immunisation and we look forward to working with health authorities to bring nirsevimab to infants as quickly as possible."
Jean-François Toussaint, Global Head of Research and Development Vaccines, Sanofi, said: "With three pivotal late-stage trials, our research has been focused on delivering a first-in-class respiratory syncytial virus prevention for all infants. Our Phase III MELODY results in healthy late preterm and term infants represent a major milestone toward that goal. We are pleased nirsevimab has the potential to become the first immunization to protect all infants across the respiratory syncytial virus season, with only a single dose."
A prespecified pooled analysis of the MELODY and Phase IIb trials demonstrated a reduction of hospitalisations caused by RSV with the proposed dose of nirsevimab.1-2,5 In term and preterm infants (greater than 28 weeks gestational age), 21 of 786 (2.7%) infants in the placebo arm compared to nine of 1,564 (0.6%) in the nirsevimab arm experienced an RSV-associated hospitalisation, giving an estimate of efficacy of 77.3% (95% CI 50.3, 89.7; P1,2,5 There was numerical reduction, although not statistically significant, of the risk of RSV associated hospitalisations observed in the MELODY trial alone (62.1%, 95% CI: -8.6, 86.8, p=0.07).1-2 In the nirsevimab arm, six of 994 (0.6%) infants were hospitalised for RSV LRTI, while eight of 496 infants (1.6)% were hospitalised in the placebo arm.1-2
The overall safety profile of nirsevimab remains consistent with previously reported results. No clinically meaningful differences in safety results between the nirsevimab and placebo groups were seen in MELODY and Phase IIb.1-2,5-6
MELODY trial results were published in the New England Journal of Medicine (NEJM). Details from the MEDLEY trial were also published in the NEJM. Regulatory submissions began in the first half of 2022.
Notes
RSV
RSV is a common, contagious virus that causes seasonal epidemics of lower respiratory tract infections (LRTI), leading to bronchiolitis and pneumonia in infants.7-9 It is also a leading cause of hospitalisations in all infants.9 Globally, in 2015, there were approximately 30 million cases of acute lower respiratory infections leading to more than three million hospitalisations, and it was estimated that there were 60,000 in-hospital deaths of children younger than five years.9-10 In recent months, there has been a resurgence of RSV following the easing of COVID-19 public health measures.11-12 Most hospitalisations for RSV occur in otherwise healthy infants born at term.13-17 Medically attended LRTIs are associated with increased costs to the healthcare system.18
MELODY
MELODY is a randomised, placebo-controlled Phase III trial conducted across 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.1-2 Healthy late preterm and term infants (gestational age ≥35 weeks 0 days) were randomised (2:1) to receive a single 50mg (in infants weighing 1-2 Pooled analyses of the RSV LRTI hospitalisation endpoint from both of the MELODY and the Phase IIb trials were prespecified under a multiplicity-protected hierarchical testing strategy.
The evaluation of the primary efficacy endpoint in the MELODY trial was conducted earlier than anticipated. Global public health measures to control COVID-19 had reduced the circulation of all respiratory viruses, including RSV, at the time of trial enrolment. Sufficient cases had been accrued prior to the pandemic to evaluate nirsevimab's ability to prevent RSV LRTI versus placebo. An additional 1,500 infants have been enrolled in the Northern and Southern Hemispheres to provide additional safety information.1-2
Medically Attended LRTI and Hospitalisation for RSV LRTI Through 150 Days Postdose (ITT population)
