GlaxoSmithKline takes RSV maternal vaccine candidate into Phase 3 study
There are currently no vaccines available for RSV. GSK is developing a portfolio of three RSV vaccine candidates, based on different novel technologies, all of which have received FDA fast-track designation.
The candidate vaccine for maternal immunisation (GSK3888550A) is the most advanced in the portfolio.
Maternal antibodies
The candidate vaccine contains a recombinant subunit pre-fusion RSV antigen (RSVPreF3). It aims to prevent medically assessed RSV-associated lower respiratory tract illnesses in infants during the first six months of life by transfer of maternal antibodies.
Maternal immunisation, notes GSK, could help to protect infants that are too young to be immunised in their first months of life – when they are most vulnerable to RSV infections. It also hopes that the polyclonal nature of the humoral response boosted by the vaccine may offer broad protection - thus keeping protection against any potential virus mutations.
In the Phase 1/2 study, carried out in women who were not pregnant, the vaccine candidate was shown to be able to rapidly boost pre-existing immunity, leading to a high level of protecting neutralising antibodies, with a 14-fold increase in RSV-A and RSV-B neutralising antibody titers observed as early as one week after immunisation.
The Phase 3 investigational RSV maternal vaccine study (GRACE) is a double-blind study in up to 10,000 pregnant women aged 18-49 years.
The trial will evaluate the efficacy of a single dose of the RSV maternal unadjuvanted candidate vaccine administered intramuscularly to pregnant women in good general maternal health aged 18-49 years for the prevention of medically assessed RSV-associated lower respiratory tract illnessess in their newborn infants.
The study will also evaluate the safety of the candidate vaccine both in vaccinated mothers and in their infants.
Interim results are expected by the second half of 2022; with the conclusion of the study estimated for early 2024.
RSV threat to infants
According to estimates, 33 million cases of RSV occur each year in children less than 5 years of age, with about 3 million hospitalised and approximately 120,000 dying from complications associated with the infection. Nearly half of these paediatric hospitalisations and deaths occur in infants less than 6 months of age.
RSV is a leading cause of respiratory infections such as bronchiolitis and viral pneumonia in infants.
Meanwhile, RSV is also a ‘significant health threat’ for older adults, with around 177,000 hospitalisations and 14,000 deaths associated with RSV infections in the US alone.
GSK’s portfolio of RSV vaccines also has a vaccine candidate for children aged 6-24 months: with the replication defective recombinant viral-vector vaccine GSK3389245A in Phase 1/2 studies.
Its third candidate is for older adults: with a recombinant protein adjuvanted candidate (GSK3844766A) due to enter a Phase 3 study in the coming months.
Emmanuel Hanon, Senior Vice President and Head of Vaccines R&D, GSK, said: “RSV burden is high among young infants – a vaccine which protects them from birth would represent significant progress in addressing the burden of RSV, preventing infant illness and families’ distress, as well as reducing the associated burden for society.
"Advancing our portfolio of RSV vaccine candidates based on robust available data is a major step towards GSK’s goal of reducing the RSV-associated disease burden around the world.”
GSK's wider vaccine portfolio includes a COVID-19 candidate which is being developed in partnership with Sanofi. The protein subunit candidate is in Phase 1/2 clinical trials; with the companies hoping to proceed to Phase 3 by the end of the year.
