Antibody Treatment Lowers Risk of Infant RSV; Maternal Vaccination Test Falls Short

By Gene Emery

July 31, 2020

(Reuters Health) - In the quest to control the respiratory syncytial virus (RSV) that plagues infants, an experimental single-dose monoclonal antibody treatment has shown promise in a new study, while a separate attempt to prevent the disease by vaccinating pregnant women has failed to show the benefit researchers had hoped to see.

RSV, which runs through the population every year, is a leading cause of infant deaths. Across the globe, it puts an estimated 3.2 million children under 5 in the hospital each year, killing about 118,000. Nearly half of those deaths are in infants under age 6 months.

Babies in low- and middle-income countries are disproportionately affected, although the virus results in the hospitalization of about 100,000 children in the U.S. annually. There is no safe and effective RSV vaccine. Ribavirin, the only approved treatment, requires five injections for an RSV season and has limited effectiveness.

In the test of AstraZeneca's monoclonal antibody therapy nirsevimab, only 2.6% of the 969 healthy preterm infants who received a single intramuscular injection developed an RSV-associated lower respiratory tract infection compared with 9.5% of the 484 babies who received a placebo injection at the start of the RSV season. That's a 70.1% reduction (P<0.001).

The research team, led by Pamela Griffin of AstraZeneca, saw a similar decline in hospitalizations for RSV infections, with rates of 0.8% among nirsevimab recipients versus 4.1% with placebo (P<0.001), a 42.5% decline.

The Griffin team said the improvement was consistent throughout the 150 days of the test, across the 23 countries where the study was done, and seemed to apply to RSV subtypes.

There was no evidence of side effects and the researchers said there were "no notable hypersensitivity reactions."

The antibodies had a half-life of 59 days.

The monoclonal antibody treatment "is a potentially very important vaccine-like approach," coauthor Tonya Villafana, global vaccines franchise chief at AstraZeneca, told Reuters Health in a telephone interview. "We think this is really an important breakthrough."

The study was done in infants born at 29 to just under 35 weeks. A test that includes non-premature babies is underway, with results expected in 2023, said Dr. Villafana.

The trial did not compare nirsevimab to MedImmune's palivizumab (Synagis), which is only recommended for high-risk infants and is given as a monthly injection.

AstraZeneca and Sanofi Pasteur, which has a co-development and co-commercialization agreement with AstraZeneca, funded the study. The results, initially released in October, were published online Wednesday in The New England Journal of Medicine.

Nirsevimab is a monoclonal antibody against the RSV's F protein, which the virus uses to fuse to the membrane of a host cell.

In the second study, as part of an attempt to prevent the disease in newborns by vaccinating their mothers during pregnancy, a separate team of researchers gave injections of the F protein to 3,051 women who had reached their 28th week of pregnancy and placebo injections to another 1,585.

During the first 90 days of life, the babies whose mothers received the monoclonal antibody experienced a lower rate of RSV infections, but the decline was not statistically significant.

The infection rate was 1.5% in the experimental vaccine group and 2.4% in the placebo group, for an efficacy of 39.4%. Chief author Dr. Shabir Madhi, professor of vaccinology at the University of the Witwatersrand in Johannesburg, South Africa, said the U.S. Food and Drug Administration had been looking for a protection rate of 50% or higher.

RSV with severe hypoxemia was seen in 0.5% of the babies whose mothers had received the vaccine versus 1.0% in the control group, for an efficacy rate of 48.3%. Hospitalization rates for RSV-associated infections were also lower with the vaccine -- 2.1% compared with 3.7% with placebo -- an efficacy rate of 44.4%.

Dr. Madhi told Reuters Health in a telephone interview that 53 women would need to be treated to prevent one childhood RSV hospitalization; 78 would need to be vaccinated to prevent one RSV hospitalization with severe hypoxia.

The phase 3 international study didn't meet the primary endpoint, but "the suggestion of a possible benefit with respect to other end-point events involving RSV-associated respiratory disease in infants warrants further study," said the team.

That's because, for example, "There was quite a difference when you looked at the efficacy of the vaccine in the low- and middle-income countries," said Dr. Madhi. The efficacy rate for preventing hospitalization was 53%. It was 69% for preventing severe hypoxemia. "It seems the vaccine would have a huge benefit" in those countries.

The reason it seems to be more effective in those regions of the world is unclear. One possibility, he said, is that mothers in those countries tended to receive their vaccination earlier.

Injection-site reactions occurred in 40.7% of vaccine recipients and 9.9% of those who received placebo. The frequencies of other side effects were similar in the experimental and control groups.

The study, financed by Novavax, also appears in The New England Journal of Medicine.

"Both approaches offer hope that an effective means for preventing RSV infections may finally be in sight," said Dr Cody Meissner of the Tufts University School of Medicine in Boston in a Journal editorial.

SOURCES: https://bit.ly/2BAyHJC, https://bit.ly/2ZYTxeN and https://bit.ly/2EkuydL The New England Journal of Medicine, online July 29, 2020.

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