An antibody against the respiratory syncytial virus (RSV) could improve outcomes for this potentially fatal paediatric virus, show phase IIb results reported in the New England Journal of Medicine.
RSV is the most common cause of lower respiratory tract disease and hospitalizations for respiratory illness in infants and young children, and results in the hospitalization of nearly 100,000 young children in the United States alone each year. AstraZeneca’s antibody palivizumab was approved as a prophylactic passive immunotherapy approach for RSV in 1998, making it the first and, as yet, only antibody approved for a virus. But the antibody, which binds the RSV envelope fusion protein, has a modest efficacy, a short half-life and high cost, which limit its utility. Other options are needed.
AstraZeneca and Sanofi’s nirsevimab may now provide a better solution. In a phase IIb trial of the antibody versus placebo, in 1,453 pre-term infants, the incidence of medically attended RSV-associated lower respiratory tract infection was 70% lower with treatment than with placebo. Whereas palivizumab has to be administered monthly to achieve a protective effect of 45–55% in infants at high risk of RSV-related hospitalization, nirsevimab was administered once.
A phase III trial of the antibody in 3,000 healthy infants is ongoing, and the partners anticipate filing for approval in 2023.
Separately, Novavax reported phase III results from its recombinant RSV F protein nanoparticle vaccine ResVax. Rather than treating infants directly, Novavax’s strategy is to vaccinate pregnant women to achieve passive immunity through the transfer of antibodies from mothers to their infants. This trial was the first ever phase III trial of a vaccine for maternal immunization licensure.
The trial enrolled 4,630 pregnant women, who received either vaccine or placebo at 28 to 36 weeks of gestation. The trial missed its primary end point, RSV-associated lower respiratory tract infection up to 90 days of life; with infection rates of 1.5% in the vaccine group and 2.4% in the placebo group, the vaccine offered an efficacy of 39%. Secondary end points, including hospitalization for RSV-associated disease, showed that the vaccine might reduce the severity of disease.
Novavax first disclosed this failure in March 2019. Regulators have since said that the company would have to run another phase III trial to secure approval. The company has yet to disclose next steps for the vaccine.
Paediatric infectious disease specialist Cody Meissner, at Tufts University School of Medicine, took an optimistic stance in a linked editorial. “Both approaches offer hope that an effective means for preventing RSV infections may finally be in sight,” he wrote.
Others are also pursuing maternal immunization approaches for RSV. Pfizer’s RSV vaccine PF-06928316 entered into phase III trials in pregnant women in June. GlaxoSmithKline’s RSV vaccine GSK3888550A is set to enter phase III trials in pregnant women later this year.
Nature Reviews Drug Discovery 19, 577 (2020)