Nirsevimab approved for RSV in newborns and infants

15th November 2022

Nirsevimab, the first broadly protective option against respiratory syncytial virus (RSV) for newborns and infants, has received approval for use in Europe, the manufacturer AstraZeneca has announced.

The vaccine, which has the brand name Beyfortus, has been approved by the European Commission for the prevention of RSV lower respiratory tract disease in newborns and infants during their first RSV season.

The product represents 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.

Approximately two-thirds of infants are infected with RSV during the first year of life, and 90% have been infected one or more times by two years of age. Moreover, the rate of hospitalisation for primary infection is approximately 0.5% but can be as high as 25%.

Produced by a collaborative effort from AstraZeneca and Sanofi, the terms of which were agreed in 2017, AstraZeneca leads all development and manufacturing activities for nirsevimab, and Sanofi leads commercialisation activities and records revenue.

Nirsevimab is a long-acting, antiviral monoclonal antibody which binds to the RSV F (fusion) protein and effectively locks the protein into the pre-fusion conformation and thus inhibiting entry of free virions into cells, as well as inhibiting spread of cell-associated virus by cell fusion. The drug is designed for all infants for protection against RSV disease from birth through their first RSV season with a single dose.

Nirsevimab clinical efficacy

In a phase IIb trial, infants were randomised in a 2:1 ratio to receive nirsevimab, at a dose of 50mg in a single intramuscular injection, or placebo at the start of an RSV season. The results showed that the incidence of medically attended RSV-associated lower respiratory tract infection was 70.1% lower with nirsevimab prophylaxis compared to placebo.

Further data came in a second trial in which infants who had been born at a gestational age of at least 35 weeks to receive a single intramuscular injection of nirsevimab or placebo (in a 2:1 ratio) before the start of an RSV season. The primary efficacy end point was medically attended RSV-associated lower respiratory tract infection through 150 days after the injection.

Medically attended RSV-associated lower respiratory tract infection occurred in 1.2% of those given nirsevimab 5.0% in the placebo group, corresponding to an efficacy of 74.5% (95% CI 49.6 – 87.1, p < 0.001).

Moreover, hospitalisation for RSV-associated lower respiratory tract infection occurred in 0.6% of those given nirsevimab compared to 1.6% in the placebo group. However, this was associated with a lower efficacy (62.1%), and which was not significant (p = 0.07).

According to the EMA, nirsevimab should be given before the RSV season or as soon as possible after birth for those infants born during the RSV season.

EMA recommends nirsevimab to protect infants from RSV

27th September 2022

Nirsevimab is recommended by the EMA for prevention of respiratory syncytial virus in newborns and infants during their first RVS season

Nirsevimab has been recommended for a marketing authorisation in the European Union for the prevention of Respiratory Syncytial Virus (RSV) lower respiratory tract disease in newborn babies and infants during their first RSV season and when there is a risk of RSV infection in the community.

Respiratory syncytial virus (RSV) is a common cause of childhood infections and which usually causes mild, cold-like symptoms. However, RSV can give rise to lower respiratory infection such as bronchiolitis and is also a major cause of hospital admissions in young children.

In 2015, for example, it was estimated that globally, there were 33·1 million episodes of RSV which led to around 3·2 million hospital admissions and 59,600 in-hospital deaths in children younger than 5 years.

While there are a number of recognised risk factors for RSV in children including prematurity, low birth weight, maternal smoking and a history of atopy, other data has revealed that among children hospitalised with RSV, 79% were previously healthy.

Nirsevimab (brand name Beyfortus) a recombinant human monoclonal antibody with an extended half-life that binds the F1 and F2 subunits of the RSV fusion (F) protein at a highly conserved epitope, locking the RSV F protein in the pre-fusion conformation and blocking viral entry into the host cell.

In a study of 1453 preterm, healthy infants, a single 50 mg dose of nirsevimab administered before the RSV season gave rise to a 70.1% lower incidence of RSV infection and a 78.4% lower incidence of hospitalisation for RSV-associated infections over an 150-day period after administration of the dose.

Nirsevimab was supported through the EMA’s PRIority Medicines (PRIME) scheme, which provides early and enhanced scientific and regulatory support to promising new medicines that address unmet medical needs. Beyfortus was also evaluated under EMA’s accelerated assessment mechanism because prevention of RSV infection in all infants is considered to be of major public health interest.

Nirsevimab clinical efficacy

The effectiveness of the monoclonal antibody was evaluated in a randomised, double-blind, placebo-controlled trial in which infants with a gestational age of at least 35 weeks were given either a single 50 mg intramuscular injection of nirsevimab (or 100 mg if their weight was above 5 kg) or placebo in a 2:1 (nirsevimab: placebo) ratio.

The primary efficacy endpoint was medically attended RSV-associated lower respiratory tract infections through to 150 days after the injection. The secondary efficacy endpoint was hospitalisation due to RSV over the same time period. A total of 1,490 infants with a median age of 2.6 months (48.4% female) were enrolled in the trial.

The primary endpoint occurred in 1.2% of those receiving nirsevimab and 5% of those given a placebo injection, corresponding to an efficacy of 74.5% (p < 0.001) and the efficacy against hospitalisation for RSV was 62.1% (p = 0.07).

According to the EMA, the opinion of the Committee for Medicinal Products for Human Use (CHMP) is an intermediary step on Beyfortus’ path to patient access. This opinion will now be sent to the European Commission for the adoption of a decision on an EU-wide marketing authorisation and once granted, decisions about price and reimbursement will take place at the level of each Member State, taking into account the potential role/use of this medicine in the context of the national health system of that country.