Pfizer’s RSV vaccine given to expectant mothers may increase risk of preterm birth, experts warn

It was feared today that a Pfizer vaccine given to expectant mothers could increase the risk of babies being born prematurely.

Experts have called for more rigorous scrutiny of the new respiratory syncytial virus (RSV) jab, which could be approved in the US and UK later this year.

It comes because GlaxoSmithKline halted its own phase three trial of its maternal RSV vaccine in February after discovering an increased risk of preterm birth in vaccinated mothers.

No safety concerns were identified by Pfizer in its own phase three trial, which was considered the final hurdle before approval by health authorities.

Still, experts told today The BMJ it was important to reassess and analyze the findings using more sensitive measures.

In the results of an interim analysis of its phase three trial last month, Pfizer said the vaccine was effective against medically managed severe RSV in children. No statistically significant differences were found in preterm birth, it confirmed. However, experts have suggested that the data needs further analysis, while the Food and Drug Administration (FDA) should also conduct post-approval monitoring, if approved

RSV is a common respiratory virus that usually causes mild, cold-like symptoms, usually in winter.

It belongs to the same family as the mumps and measles viruses.

Pfizer’s maternal RSV vaccine aims to protect babies against serious illnesses caused by the virus. While not yet approved, if approved, it would be offered to women who are six to nine months pregnant.

RSV is very common, but can be fatal, especially in young children.

In 2019, an estimated 3.6 percent of all deaths worldwide in children aged one to six months were due to RSV, with 97 percent of these deaths occurring in low- and middle-income countries.

The vaccine has not yet been approved for use, but a decision from the US Food and Drug Administration (FDA) is expected in August.

The European Medicines Agency will also make an approval decision later this year.

In the results of an interim analysis of the phase three trial last month, Pfizer said the vaccine was effective against medically managed severe RSV in children.

No statistically significant differences were found in preterm birth, it confirmed.

However, experts have suggested that the data needs further analysis, while the FDA should also conduct post-approval review, if approved.

Professor Klaus Überla, director of the Virological Institute at Erlangen University Hospital and member of the RSV working group of the Standing Committee on Vaccination, told the BMJ: ‘My interpretation of all this data is that there may be a safety signal for preterm birth. that must be followed.’

Meanwhile, Professor Cody Meissner, a pediatrician at Dartmouth Geisel School of Medicine and consultant in the Centers for Disease Control and Prevention’s (CDC) Maternal RSV Working Group, predicted that potential adverse effects, such as preterm births, “will be closely monitored” . in review programs by FDA and CDC.

He added: “We need a safe vaccine.”

Another scientist from the US National Institutes of Health, who was not authorized to speak to the media, also recommended analyzing Pfizer data using more sensitive measures, such as mean birth weight and subgroup analyzes to detect possible signs.

Work on an RSV vaccine has run into roadblocks for decades after multiple failures in clinical trials.

This includes a study in the 1960s where children given an experimental vaccine experienced worse disease than those in the placebo arm. Two young people, both less than two years old, were killed.

Research later found that this was because the vaccine had targeted a version of the protein on the virus that forms after it fused to a cell, meaning it failed to elicit protection against the disease and may have even hampered the immune response.

In February, GSK halted its phase three trial of the maternal RSV shot, citing safety concerns.

In a paper submitted to the FDA, GSK’s data showed an increase in preterm birth in vaccinated mothers (6.8 percent) compared to those who received the placebo (4.9 percent).

It accounted for one extra premature birth for every 54 mothers vaccinated.

About 13 neonatal deaths were also recorded among those vaccinated.

Only three were reported in the placebo group.

However, Ilse Dieussaert, vice president of vaccine development at GSK, said the increase in neonatal deaths was due to deaths in premature babies.

There was no imbalance in deaths in term babies, she noted.

The number of premature babies was highest in low- and middle-income countries, she noted. Almost no difference was observed in high-income countries.

Earlier this week, the first-ever RSV vaccine in the US was approved by the FDA after giving the go-ahead for the vaccine to be administered to adults age 60 and older.