Nirsevimab showed a significant reduction in medically-attended lower respiratory tract infections (LRTI) and hospitalisations caused by respiratory syncytial virus (RSV) in healthy preterm infants in a positive Phase IIb trial published in the New England Journal of Medicine.
The trial demonstrated for the first time that a single-dose monoclonal antibody (mAb) can significantly reduce medically-attended RSV LRTI, including bronchiolitis and pneumonia, in infants throughout the full RSV season.
Nirsevimab is an extended half-life RSV mAb, being developed by AstraZeneca and Sanofi as a passive immunisation, with the potential to provide immunity directly to infants and offer immediate protection against RSV.
On the primary endpoint, nirsevimab achieved a statistically significant 70.1% reduction in medically-attended RSV LRTI compared to placebo through 150 days post-dose. On the secondary efficacy endpoint, nirsevimab achieved a 78.4% relative reduction in the incidence of hospitalisations due to RSV LRTI compared to placebo through 150 days post-dose. The safety profile for nirsevimab was similar to placebo, with no notable hypersensitivity reactions observed.
Dr Joseph Domachowske, study author, Professor of Paediatrics and Microbiology and Immunology at the State University of New York Upstate Medical University, US, said: “The data for nirsevimab are exciting, as they highlight the potential for this innovative approach to protect infants from RSV with just one injection for the entire season. Nirsevimab offers the important potential to reduce hospitalisations and emergency department and in-office visits, which are a significant burden for healthcare systems.”
Mene Pangalos, Executive Vice President, R&D BioPharmaceuticals, AstraZeneca, said: “Every year, respiratory syncytial virus leads to more than three million hospitalisations worldwide and to a significant number of emergency visits for children under five. This novel monoclonal antibody has the potential to protect a broad infant population, 90% of whom are infected with the virus before their second birthday.”
Serious adverse events were reported in 11.2% of nirsevimab and 16.9% of placebo recipients, and none were considered to be related to nirsevimab.
In February 2019, the US Food and Drug Administration granted Breakthrough Therapy Designation for nirsevimab for the prevention of LRTI caused by RSV, and the European Medicines Agency (EMA) granted access to its PRIority MEdicines (PRIME) scheme for the same indication.
In July 2019, AstraZeneca initiated pivotal Phase III and Phase II/III trials to assess the safety and efficacy of nirsevimab to prevent LRTI caused by RSV in full-term, healthy late preterm and high-risk infants. The trials will be conducted in more than 350 sites across the US, Canada, Europe, Asia and the Southern Hemisphere.
RSV is a common, contagious virus that infects the respiratory tract, causing millions of hospitalisations globally, and is the most common cause of bronchiolitis and pneumonia in children younger than one year in the US.4,5,6 Globally, in 2015, there were approximately 33 million cases of acute lower respiratory infections causing more than three million hospitalisations, and it was estimated that there were 60,000 in-hospital deaths of children younger than five years. Approximately 80% of babies who are hospitalised due to RSV are otherwise healthy. Moreover, medically-attended LRTIs are associated with increased costs to the healthcare system.
The Phase IIb trial
Healthy preterm infants of 29–35 weeks’ gestation were randomised (2:1) to receive a single 50mg intramuscular injection of nirsevimab or placebo. Between November 2016 and December 2017, 1,447 infants were dosed (nirsevimab, n=966; placebo, n=481) at the RSV season start. The primary endpoint was the incidence of medically-attended RSV LRTI through 150 days post-dose. Medically-attended means any case of RSV LRTI that is seen by a healthcare provider. The secondary efficacy endpoint was the incidence of hospitalisation due to RSV LRTI through 150 days post-dose. Research was conducted by AstraZeneca in both hemispheres, at 164 sites in 23 countries.
Nirsevimab is an extended half-life RSV mAb being developed as a passive immunisation for the prevention of LRTI caused by RSV. It is being developed for use in a broader infant population than the current standard of care, including for use in all infants experiencing their first RSV season and for infants with congenital heart disease or chronic lung disease entering their first and second RSV season.6,7 While nirsevimab may only require one dose during a typical five-month RSV season, the current anti-RSV antibody, Synagis (palivizumab), is limited to high-risk infants and provides one-month protection, requiring five injections to cover an RSV season.
Nirsevimab is a passive immunisation, whereby an antibody is given directly to an infant to help prevent RSV, unlike active immunisation, where a person’s immune system is activated to prevent or fight infection through a vaccine. Passive immunisation could offer immediate protection unlike active immunisation, which can take weeks to develop protection.
In March 2017, AstraZeneca and Sanofi announced an agreement to develop and commercialise nirsevimab. Under the terms of the agreement, AstraZeneca leads all development activity through initial approvals and retains manufacturing activities and Sanofi will lead commercialisation activities.
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