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RSV: UK to examine whether to offer monoclonal antibody routinely to all babies

BMJ 2022; 379 doi: (Published 11 November 2022) Cite this as: BMJ 2022;379:o2725
  1. Jacqui Wise
  1. Kent

Nirsevimab has received regulatory approval in the UK, and researchers will now assess its benefits in protecting babies from serious illness from respiratory syncytial virus, as Jacqui Wise reports

The UK’s Medicines and Healthcare Products Regulatory Agency has approved nirsevimab, a long acting monoclonal antibody, to protect newborn babies against respiratory syncytial virus (RSV) lower respiratory tract disease. The European Medicines Agency gave its approval earlier this month.1

Approval was based on the results of two studies published in the New England Journal of Medicine showing that nirsevimab has a good safety and efficacy profile in preterm and full term infants.234 One trial in 1490 healthy infants showed that a single injection of nirsevimab, in comparison with placebo, produced a 74.5% reduction in RSV associated lower respiratory tract infections needing medical care.

However, the preventive injection won’t be offered routinely to all babies in the UK until more data are available on whether it prevents hospital admissions for RSV. A new trial, Harmonie, is trying to answer that question.5 This study hopes to recruit more than 20 000 infants up to 12 months in the UK, Germany, and France.

A collaboration between the UK National Institute for Health and Care Research and the drug companies Sanofi and AstraZeneca, the study will last around 12 months, with the results expected soon after.

RSV infection rates are currently higher in the UK than during the covid pandemic but are still in line with a normal winter. Data from 10 November 2022 show that admissions to hospital of children with RSV have been broadly steady in the past few weeks, with the highest positivity in the under 5 year age group, at 26.3%.6 However, in the US the incidence of RSV infections is surging, and experts are warning of a triple epidemic of flu, RSV, and covid-19.7

Infant hospital admissions

RSV is one of the world’s leading causes of admission of infants to hospital and affects 90% of children before the age of 2. It often causes only mild illnesses, such as a cold. However, in some babies it leads to more severe lung problems such as bronchiolitis and pneumonia.

“What we can’t do is predict which infants are going to end up in hospital with RSV or go on to intensive care versus those babies which will just get it as a relatively mild disease,” Simon Drysdale, joint chief investigator of the study, told a media briefing.

Four fifths of babies who end up in hospital have no underlying problems, said Drysdale, a consultant paediatrician in infectious diseases at St George’s University Hospital NHS Foundation Trust in London. “There are some risk factors for severe disease: those babies who are born very prematurely, those with significant underlying heart or lung problems or immunodeficiency. But most babies who end up in hospital are otherwise fit and well.”

In the UK RSV produces a significant burden on healthcare, with 87 deaths, 29 000 hospital admissions, and 900 intensive care admissions every year.8 It also contributes to the workload of GPs, with almost half a million primary care attendances a year. Healthcare costs associated with RSV in children under 5 years old amount to £54m a year or £87 per year per child, Drysdale said.

Limited treatment options

The only currently available preventive treatment for RSV is palivizumab, a monoclonal antibody developed in the 1990s, which is used in a very small number of high risk infants. However, this requires monthly injections over five months. Current treatment is supportive care only; there is no widely used antiviral.

There is currently no licensed vaccine for RSV in infants, although a few are in development. In October GSK published results for a vaccine candidate showing a 94.1% reduction in severe RSV disease among older adults over 60 years.9

Another possibility is vaccinating pregnant women to protect their newborns. Earlier this month Pfizer announced results of its maternal RSV vaccine in a press release.10 This claimed that Pfizer’s study, which has not been peer reviewed, showed that giving the vaccine to pregnant women reduced the risk of severe lower respiratory tract illness from RSV in infants in the first six months of a baby’s life.

“Maternal vaccination would protect babies in the first 2-3 months of life,” said Saul Faust, professor of paediatric immunology and infectious diseases at the University of Southampton and also a Harmonie investigator. “But whether all mums will accept the vaccine in pregnancy is not known.”

Nirsevimab is an antiviral monoclonal antibody that has been designed to attach to the protein that RSV needs to infect the body. When it is attached, the virus becomes unable to enter the body’s cells. Because the drug is removed slowly from the body, over a period of several months, a single dose can protect against RSV disease for the entire RSV season. “It works instantly as soon as it has been injected,” said Drysdale.

By contrast, vaccines work by prompting the body’s immune system to produce antibodies, which can take a month or two to build up. Vaccines are also not usually given to babies in the first couple of months of life. “If you give a vaccine the baby may still be vulnerable for the first crucial two months, which is one of the highest risk periods for RSV,” Drysdale added.

More data needed

The UK Joint Committee on Vaccination and Immunisation will look at all RSV technologies before deciding whether to routinely offer nirsevimab to newborn babies.

Faust said that both maternal vaccination and giving an injection of a monoclonal antibody at birth offered protection in the critical first two months. “Until we have all the data available on the impact on hospitalisations, policy makers will find it difficult to make a decision,” he said.

“We will probably need all options available as part of our armoury. We may well end up with different things being done at different times of year and possibly in different groups of patients—mums, babies, and older children—to get as wide a protection as possible.”