Novavax has reported topline data from two clinical trials of its RSV F-protein recombinant nanoparticle vaccine candidate (RSV F Vaccine) in older adults.
The Resolve trial, which is a Phase 3 trial of the RSV F Vaccine in 11,856 adults who are 60 years of age and older, did not meet the pre-specified primary or the secondary efficacy objectives, and did not demonstrate vaccine efficacy.
The trial was a randomised, observer-blinded, placebo-controlled that was conducted at 60 sites in the US.
The primary aim of the Resolve trial was to demonstrate efficacy in the prevention of moderate-severe RSV-associated lower respiratory tract disease (RSV msLRTD), as defined by the presence of multiple lower respiratory tract symptoms.
The secondary objective of the trial was to show of the RSV F Vaccine in reducing the incidence of all symptomatic respiratory disease due to RSV (RSV ARD).
Finally, the trial also reviewed the safety of the unadjuvanted, 135 microgram dose of the RSV F Vaccine compared to placebo.
Novavax president for research and development Gregory Glenn said: "We are both surprised and disappointed by the outcome of the Resolve trial, which we recently unblinded.
"Our initial analyses and review of the key aspects of the trial do not indicate issues with trial execution, data collection, data integrity, or drug product quality.
"We expect to have preliminary immunogenicity data in the coming weeks to further our understanding of the trial results.
“Historically, annual seasonal RSV ARD attack rates between 3% and 7% have been observed in older adults1.
"In our Phase 2 trial, we observed an RSV ARD attack rate of 4.9% and an RSV msLRTD attack rate of 1.8%.
"In contrast, we observed an RSV ARD attack rate of 2.0% and an msLRTD attack rate of 0.4% in our Phase 3 trial.
"These attack rates indicate a mild RSV season in older adults this year.
"We are continuing to investigate potential root causes that could have impacted the outcome of this trial.
Novavax also reported topline results from the Phase 2 rollover clinical trial of its RSV F Vaccine in older adults.
This was a randomised, observer-blinded, placebo-controlled rollover trial that saw enrollment of 1,329 older adults from the previous Phase 2 trial, conducted at the same ten sites in the US.
The primary aims of the trial evaluated safety and serum anti-F IgG antibody concentrations in response to immunisation with the RSV F Vaccine.
The exploratory objectives of the trial evaluated the efficacy of a second annual dose of the RSV F Vaccine in the prevention of RSV ARD and RSV msLRTD.
Participants earlier randomised to receive 135 microgram RSV F Vaccine or placebo were re-enrolled and re-randomised in the current trial to receive either 135 microgram RSV F Vaccine or placebo.
The analysis had four separate trial arms: a) participants receiving a placebo in both the first trial and second trial; b) participants receiving RSV F Vaccine in the first trial and placebo in the second trial (vaccine-placebo); c) participants receiving placebo in the first trial and RSV F Vaccine in the second trial (placebo-vaccine); and d) participants receiving RSV F Vaccine in both the first trial and second trial (vaccine-vaccine).
Glenn stated: “The rollover trial demonstrated immunogenicity in all active vaccine recipients."
He continued: "There was higher anti-F IgG at baseline in the Vaccine-Vaccine arm compared to the Placebo-Vaccine arm.
Further, the Vaccine-Vaccine arm showed a greater than 2-fold increase in anti-F IgG from the higher baseline.
We observed similar low-attack rates and absence of efficacy of a single immunisation in this trial as was observed in Phase 3 Resolve trial, although we did observe that a second season immunization could provide efficacy.
"The event rate comparisons made to either placebo groups suggested that the second season immunsation was protective, even in a year with a very low-attack rate.
"Further understanding of these data may come forth with full evaluation of the immune responses.”
Novavax president and CEO Stanley C. Erck said: “While the results from the Resolve trial are unexpected, we continue to believe in our technology and product candidates based on the totality of the data from our RSV F Vaccine franchise.
“We expect to gain a better understanding of the data from both the Phase 2 rollover and Phase 3 trials as we further analyse and review them internally, as well as with our investigators and potential partners.”