Home Medizin Risiko einer Frühgeburt stoppt RSV-Impfstoffversuch für Mütter

Risiko einer Frühgeburt stoppt RSV-Impfstoffversuch für Mütter

von NFI Redaktion

A Phase 3 study testing a maternal vaccine candidate against Respiratory Syncytial Virus is terminated early due to a higher risk of preterm births in the vaccine candidate group compared to the placebo group.

When enrollment was halted on February 25, 2022 due to a preterm birth safety signal, 5,328 pregnant women had been vaccinated – about half of the intended 10,000 enrollments. Of these, 3,557 received the maternal vaccine candidate RSV Prefusion F Protein and another 1,771 received a placebo.

Data from the GSK-sponsored study were made available immediately when recruitment and vaccination were stopped, followed by an investigation into the preterm birth risk. The results of this analysis led by Ilse Dieussaert, MD, Vice President of Vaccine Development at GSK in Wavre, Belgium, will be published online on March 13 in The New England Journal of Medicine.

„We have discontinued our work on this RSV maternal vaccine candidate and are closing all ongoing studies, except for the MAT-015 follow-up study for monitoring subsequent pregnancies,“ said a GSK spokesperson in an interview.

The study was conducted on pregnant women aged 18 to 49 years to evaluate the effectiveness and safety of the vaccine. The women were randomly assigned in a 2:1 ratio to receive either the vaccine candidate or a placebo between the 24th and 34th week of pregnancy.

Preterm Births

The primary outcomes were all or severe medically assessed RSV-associated lower respiratory tract infections in infants from birth to 6 months of age, and safety in infants from birth to 12 months of age.

According to the data, 6.8% of infants in the vaccine group experienced preterm birth compared to 4.9% in the placebo group (relative risk [RR] 1.37; 95% confidence interval [CI] 1.08 to 1.74; P=0.01). Newborn deaths were 0.4% in the vaccine group and 0.2% in the placebo group (RR: 2.16; 95% CI: 0.62 to 7.56; P=0.23).

So far, only one RSV vaccine (Pfizer’s Abrysvo) is approved for use during pregnancy to protect infants from RSV-associated lower respiratory tract infections.

„It was a big deal that this process was halted and the new candidate did not receive approval,“ says Aaron E. Glatt, MD, Chair of Medicine and Chief of Infectious Diseases and Hospital Epidemiologist at Mount Sinai South Nassau in Oceanside, New York.

Only one RSV vaccine approved for pregnancy

Glatt points out that the GSK vaccine is similar to the actually approved vaccine for mothers. „The data clearly show a slight, but increased risk of preterm labor,“ says Glatt, „and although not as clearly demonstrated, there was an increase in neonatal deaths in the very small numbers in the group, which is concerning for all neonatal deaths.“

The impacts are concerning, he says: „You’re giving this vaccine to prevent.“ While the Pfizer vaccine, which has been approved, showed a very slight increase in preterm births, the risk was not statistically significant, he emphasizes, „and it showed similar benefits in preventing potentially lethal neonatal conditions.“

Glatt says there are still concerns regarding the approved vaccine, and he explains that most doctors would administer it towards the end of the recommended 34-week window. „Even if there’s a slight increase in preterm labor, it’s unlikely to have serious consequences that way, as the baby is already far enough along.“

A difference in the incidence of preterm births between the experimental vaccine and placebo group was mainly seen in low- and middle-income countries, „where about 50% of the study population was enrolled and where there was a medical need for maternal assistance.“ RSV vaccines are essential.

The relative risk was 1.56 (95% CI: 1.17–2.10) for low- and middle-income countries and 1.04, 95% CI: 0.68–1.58 in high-income countries.

„If a smaller percentage of participants from low- and middle-income countries had participated in our study, the relative risk of preterm birth in the vaccine group compared to the placebo group in the overall study population would have been lower,“ the researchers report.

The authors explain that the data do not reveal the cause of the increased risk of preterm births in the vaccine group.

„We don’t know what caused the signal,“ added the company spokesperson. „GSK completed all necessary steps in product development, including preclinical toxicological studies and clinical studies on non-pregnant women, before starting studies on pregnant women. No safety signals were identified in any of the previous parts of the clinical trials. There were no safety signals identified in other Phase 3 studies for this vaccine candidate.“

The researchers found no association between preterm births in the treatment group and control group with the gestational age at the time of vaccination or specific batch numbers from clinical vaccine studies, race, ethnicity, maternal smoking, alcohol consumption, body mass index, or the time between study vaccination and delivery, says the GSK spokesperson.

The spokesperson noted that the discontinued vaccine differs from the currently approved adjuvanted RSV vaccine (Arexvy) from GSK for adults aged 60 and over.

What’s next for other vaccines?

Maternal vaccines have been shown to be effective in preventing other diseases in infants such as tetanus, influenza, and pertussis, but RSV is a virus for which developing a vaccine is very challenging, says Glatt.

The need to have more than one option for a maternal RSV vaccine is significant, he adds, to alleviate potential concerns about supply.

„People need to be aware of how severe RSV can be in infants,“ he says. „It can be a deadly disease. It can be a severe illness even in healthy children.“

Related Posts

Adblock Detected

Please support us by disabling your AdBlocker extension from your browsers for our website.