Recommendation is based on the Beyfortus clinical trial programme which demonstrated protection against RSV disease during the RSV season with a single dose
If approved by the European Commission, Beyfortus would be the first preventative option for the broad newborn and infant population
AstraZeneca and Sanofi’s Beyfortus (nirsevimab) has been recommended for marketing authorisation 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. If approved, Beyfortus would be the first and only single-dose passive immunisation for the broad infant population, including those born healthy, at term or preterm, or with specific health conditions.
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Authority based its positive opinion on results from the Beyfortus clinical development programme, including the MELODY Phase III, MEDLEY Phase II/III, and Phase IIb trials.1-8
In the MELODY and Phase IIb trials, Beyfortus met its primary endpoint of reducing the incidence of medically attended lower respiratory tract infections (LRTI) caused by RSV during the RSV season vs. placebo with a single dose.1-6 No clinically meaningful differences in safety results between the Beyfortus and placebo groups were seen. Beyfortus 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.7-8
Iskra Reic, Executive Vice President, Vaccines and Immune Therapies, AstraZeneca, said: “This positive CHMP opinion underscores Beyfortus’ potential as a ground breaking, first-in-class passive immunisation that could transform the medical community’s approach to respiratory syncytial virus prevention in infants.”
Jean-François Toussaint, Global Head of Research and Development Vaccines, Sanofi, said: “Today’s positive CHMP opinion is one of the most significant public health achievements in respiratory syncytial virus in decades and has the potential to alleviate the enormous physical and emotional burden that RSV can place on families and healthcare systems. With this endorsement, we are one step closer to achieving our goal of protecting all infants against RSV with a single dose.”
RSV is the most common cause of LRTIs and a leading cause of hospitalisation in all infants.9-11 RSV-related direct medical costs, globally — including hospital, outpatient and follow-up care — were estimated at €4.82 billion in 2017.12 The current standard of care for the prevention of serious LRTIs caused by RSV focuses on to preterm infants and infants at higher risk of severe disease, and treatment is limited to symptomatic relief.13-14
Beyfortus (nirsevimab), an investigational 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.15 The recommended dose of Beyfortus is a single intramuscular injection of 50 mg for infants with body weight <5 kg and a single intramuscular injection of 100 mg for infants with body weight ?5 kg.
Beyfortus has 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. Beyfortus has not been approved by any regulatory authority.
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.3-4
The dosing regimen was recommended based on further exploration of the Phase IIb data.3 The subsequent Phase III study, MELODY, applied the recommended dosing regimen.2
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.1-2
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.7-8 Between July 2019 and May 2021 approximately 918 infants entering their first RSV season were randomised to receive a single 50mg (in infants weighing <5kg) or 100mg (in infants weighing ?5kg) intramuscular injection of Beyfortus or Synagis. Safety was assessed by monitoring the occurrence of TEAEs and TESAEs through 360 days post-dose.7-8 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.7 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.1-8 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.3-4 Data was published in NEJM in July 2020.
Medically Attended LRTI and Hospitalisation for RSV LRTI Through 150 Days Postdose (ITT population)
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