Therapeutics: nirsevimab for RSV prophylaxis

Respiratory syncytial virus (RSV) is a common and contagious virus that infects the respiratory tract

It is a particular health burden in the infant population and a significant cause of bronchiolitis and pneumonia.

Worldwide, it is estimated that there are more than 30 million cases of acute lower respiratory infections and three million hospitalisations a year, with 60,000 in-hospital deaths of children younger than 5 years old. About 80% of all babies hospitalised with RSV are otherwise healthy.

AstraZeneca and Sanofi are developing nirsevimab, a monoclonal antibody with a modified Fc region to extend its half-life that is designed to give passive immunisation in infants to prevent lower respiratory tract infections resulting from RSV.1

Compared with the existing anti-RSV antibody, palivizumab, it may require a single dose to confer protection for a whole RSV season; palivizumab has to be dosed monthly for the 5 months of the season and is limited to high-risk infants.

A Phase I first-in-human trial was done with 136 healthy adults.2 Subjects were given single doses of 300, 1000 or 3000 mg, intravenously, 100 or 300 mg, intramuscularly, or a placebo, and monitored for 360 days.

The safety profile was similar for both the active and placebo doses, with a time to maximum concentration following intramuscular dosing of 5–9 days.

In a Phase Ib/IIa dose escalation trial, healthy preterm infants with a gestational age of 32–35 weeks were given single intramuscular injections of 10, 25 or 50 mg of the antibody or a placebo.3

Its serum half-life ranged from 62–73 days and, on day 151, 87% of the infants in the 50 mg group still had serum concentrations above the 90% effective concentration target level of 6.8 µg/mL; 90% had at least a four-fold rise from baseline in serum RSV-neutralising antibody levels.

A Phase IIb trial has also been reported.4 A group of 1447 preterm (29–35 weeks) infants were randomised to receive a single 50 mg intramuscular injection of nirsevimab or a placebo.

It gave a 70% reduction in medically attended lower respiratory tract infections and hospitalisations from RSV compared with the placebo for up to 150 days after dosing.

There was also a 78% relative reduction in the incidence of hospitalisations from these infections. Its safety profile was similar to the placebo and no notable hypersensitivity reactions were seen.

Serious adverse events were reported in 11% and 17% of the treated and placebo subjects, respectively; none were considered to be related to the antibody. Phase II/III and Phase III trials are now under way.

References

  1. Q. Zhu, et al., Sci. Transl. Med. 9(388), eaaj1928 (2017).
  2. M.P. Griffin, et al., Antimicrob. Agents Chemother. 61, e01714 (2017).
  3. J.B. Domachowske, et al., Pediatr. Infect. Dis. J. 37, 886 (2018).
  4. M.P. Griffin, et al., N. Engl. J. Med. 383, 415 (2020).

Companies