AstraZeneca and Sanofi's Beyfortus (nirsevimab) has been approved in the European Union (EU) for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in newborns and infants during their first RSV season.1Beyfortus is the first and only single-dose RSV passive immunisation for the broad infant population, including those born healthy, at term or preterm, or with specific health conditions.
RSV is a common and highly contagious seasonal virus, infecting nearly all children by the age of two.2,3
The European Commission is the first regulatory body to grant approval to Beyfortus.1 The approval was based on results from the Beyfortus clinical development programme, including the MELODY Phase III, MEDLEY Phase II/III and Phase IIb trials,1,4-11and follows the recommendation by The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency in September 2022.12
In the pivotal MELODY efficacy trial, Beyfortus met its primary endpoint of reducing the incidence of medically attended lower respiratory tract infections (LRTI) caused by RSV by 74.5% (95% CI 49.6, 87.1; p1,4-9Beyfortus also demonstrated a comparable safety and tolerability profile to Synagis (palivizumab) in the MEDLEY Phase II/III trial, with occurrence of treatment emergent adverse events (TEAEs) or treatment emergent serious adverse events (TESAEs) similar between groups.1,10-13
Silke Mader, Chairwoman of the Executive Board and Co-founder of the European Foundation for the Care of Newborn Infants (EFCNI), said: "Respiratory syncytial virus represents a health threat among infants, and each year we see the impact it can have on families, healthcare providers and the healthcare system. At EFCNI, we are excited about the opportunity to expand prevention efforts to all infants, as we believe this can help ease the current emotional, physical and financial burdens of RSV."
Iskra Reic, Executive Vice President, Vaccines and Immune Therapies, AstraZeneca, said: "Beyfortus is the first single-dose preventative option against respiratory syncytial virus to gain approval in Europe and is also the first and only preventative option approved for a broad infant population. Today's marketing authorisation of Beyfortus marks a significant achievement for the scientific community and addresses a persistent, global unmet need in RSV prevention."
Thomas Triomphe, Executive Vice President, Vaccines, Sanofi, said: "Today is a landmark day for RSV prevention, as decades of research and development come together in the world's first approval of a broadly protective option against respiratory syncytial virus disease. Once launched, Beyfortus will offer parents the ability to help protect their babies during their first RSV season."
RSV is the most common cause of LRTI, including bronchiolitis and pneumonia in infants.14 It is also a leading cause of hospitalisation in all infants.15-18 Globally, in 2019, there were approximately 33 million cases of acute lower respiratory infections leading to more than three million hospitalisations, and it was estimated that there were 26,300 in-hospital deaths of children younger than five years.19 RSV-related direct medical costs, globally - including hospital, outpatient and follow-up care - were estimated at €4.82 billion in 2017.21
Notes
Beyfortus
Beyfortus (nirsevimab), a long-acting antibody designed for all infants for protection against RSV disease from birth through their first RSV season with a single dose, is being developed jointly by AstraZeneca and Sanofi using AstraZeneca's YTE technology.
Beyfortus has been developed to offer newborns and infants direct RSV protection via an antibody to help prevent LRTI caused by RSV. Monoclonal antibodies do not require the activation of the immune system to help offer timely, rapid and direct protection against disease.20
Beyfortus has been granted marketing authorisation in the European Union for the prevention of RSV LRTI disease in newborns and infants from birth during their first RSV season. The recommended dose of Beyfortus is a single intramuscular injection of 50 mg for infants with body weight 12
Beyfortus has also been granted regulatory designations to facilitate expedited development by several 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 Food and Drug Administration; access granted to the European Medicines Agency (EMA PRIority Medicines (PRIME) scheme; and named "a medicine for prioritized development" under the Project for Drug Selection to Promote New Drug Development in Pediatrics by the Japan Agency for Medical Research and Development (AMED). The safety and efficacy of Beyfortus was evaluated under an accelerated assessment procedure by the EMA.
Pivotal clinical trials
The Phase IIb study was a randomised, placebo-controlled trial designed to measure the efficacy of Beyfortus (nirsevimab) against medically attended LRTI through 150 days postdose. Healthy preterm infants of 29-35 weeks' gestation were randomised (2:1) to receive a single 50mg intramuscular injection of Beyfortus or placebo.1,4,5
The dosing regimen was recommended based on further exploration of the Phase IIb data. The subsequent Phase III study, MELODY applied the recommended dosing regimen.1,3,6
The MELODY Phase III study was a randomised, placebo-controlled trial conducted across 21 countries designed to determine efficacy of Beyfortus against medically attended LRTI due to RSV confirmed by reverse transcriptase polymerase chain reaction testing through 150 days after dosing, versus placebo, in healthy late preterm and term infants (35 weeks gestational age or greater) entering their first RSV season.1-3
MEDLEY was a Phase II/III, randomised, double-blind, Synagis-controlled trial with the primary objective of assessing safety and tolerability for Beyfortus in preterm infants and infants with congenital heart disease (CHD) and/or chronic lung disease of prematurity (CLD) eligible to receive Synagis.1,8,9 Between July 2019 and May 2021 approximately 918 infants entering their first RSV season were randomised to receive a single 50mg (in infants weighing Beyfortus or Synagis. Safety was assessed by monitoring the occurrence of TEAEs and TESAEs through 360 days post-dose.1,8,9 Serum levels of Beyfortus 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. Data was published in the New England Journal of Medicine (NEJM) in March 2022.
The results of MELODY, MEDLEY Phase II/III and the Phase IIb trials demonstrate that Beyfortus helps protect infants during their first RSV season against RSV disease with a single dose.1-9 This all-infant population includes preterm, healthy late preterm and term infants, as well as infants with specific conditions.
These trials form the basis of regulatory submissions which began in 2022.
Results from the Phase IIb trial
The primary endpoint of the Phase IIb study was met, reducing the incidence of medically attended LRTI, caused by RSV by 70.1% (95% CI: 52.3, 81.2) compared to placebo. Between November 2016 and December 2017, 1,453 infants were randomised (Beyfortus, n=969; placebo, n=484) at the RSV season start. Research was conducted by AstraZeneca in both hemispheres, at 164 sites in 23 countries.1,4,5 Data was published in NEJM in July 2020.
Medically Attended LRTI and Hospitalisation for RSV LRTI Through 150 Days Postdose (ITT population)
