Despite their benefits, new therapies for respiratory syncytial virus (RSV) may accelerate the emergence of drug-resistant strains, according to a new report on Monday.
Given the large market potential and high unmet need for new RSV therapies, drug developers have been focused on new vaccine and monoclonal antibody (mAb) development.
A vaccine for RSV is yet to be approved anywhere around the globe. Recently, pharma giants Pfizer and GSK developed RSV vaccines for older adults. These have also gained positive recommendations from the US Food and Drug Administration’s Vaccines and Related Biological Products Advisory Committee.
“Drug developers and regulators should proceed with extreme caution while bringing new RSV vaccines and mAbs to market, to avoid the potentially serious consequences of inducing novel viral mutations and drug-resistant strains of RSV,” said Nancy Jaser, Pharma Analyst atAGlobalData, a data and analytics company, in a statement.
As an RNA virus, like SARS-CoV-2, RSV is highly prone to mutations, especially while under pressure from mAbs.
In November 2022, AstraZeneca/Sanofi’s new mAb, nirsevimab, was approved for use in infants in the EU and the UK.
Prior to this, AstraZeneca’s Synagis (palivizumab), approved in 1998 to prevent RSV in high-risk infants, was the only approved option and dominated the global RSV market.
However, this has caused RSV to mutate, resulting in palivizumab-resistant RSV strains.
“Since palivizumab was used widely in infants for over two decades, the emergence of resistant RSV variants is not surprising. However, given the limited therapeutic options, drug-resistant RSV strains may pose a significant threat to public health,” Jaser said.
Nirsevimab has also led to antibody-resistant mutations despite its very recent approval in only two regions, the report said.
Increased viral resistance to both palivizumab and nirsevimab leaves high-risk infants in an extremely vulnerable position, without any “guaranteed” protection against RSV.
The possibility of viral escape from nirsevimab is a serious concern, especially as Pfizer and GSK’s RSV vaccines for older adults are expected to gain approval in May 2023.
It is unknown if novel vaccines will have any effect regarding resistance to mAbs. Since RSV has not yet circulated through large populations of vaccinated individuals, the widespread viral response of RSV to vaccines remains unpredictable.
“Given the lack of vaccines and therapies for high-risk infants, the risks of inducing more drug-resistant RSV strains should be avoided until new and effective prophylactic options also become available for this vulnerable population,” Nancy said.
“Constant surveillance for new mutations and variations in RSV sequences will be critical to ensure that current mAbs remain effective against circulating RSV strains while vaccines begin to enter the market,” she added.
