Covid-19 social distancing measures are likely to impede global clinical development in RSV

GlobalData Healthcare 6 April 2020 (Last Updated April 6th, 2020 15:31)

Covid-19 social distancing measures are likely to impede global clinical development in RSV

With the continued global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19, an estimated third of the global population has been instructed to practice social distancing or put in lockdown.

While these measures have been put in place to slow the spread of Covid-19, a knock-on effect has been observed in a reduction of infections from other circulating seasonal respiratory viruses, including respiratory syncytial virus (RSV). Seasonal viruses are spread through similar routes of transmission as Covid-19 and the infection control measures of handwashing and isolating if infected are announced by public health bodies annually to the public. While the reduction in circulating viruses is positive for a population with an already stretched health system, an unforeseen effect may be observed by companies conducting clinical trials investigating RSV candidate vaccines and treatments.

The current big players in the RSV vaccine market, GlaxoSmithKline, Johnson & Johnson, and Pfizer, all have large Phase II studies ongoing for their candidates. Social distancing will likely mean fewer participants are exposed to RSV, and fewer cases of RSV will be seen in all arms of the trial. Vaccine clinical development is often troubled by failure to demonstrate protective efficacy, and this is particularly a problem for infectious diseases with low prevalence. The only RSV candidate vaccine to reach Phase III development, Novavax’s maternal immunization candidate ResVax, did not achieve its primary endpoint in early 2019. Consequently, the only option a company may have is to extend trials, to include RSV seasons in 2021 or 2022 that hopefully will not be impacted by COVID-19–related infection control measures; if not, vaccine developers risk the possibility of missing the primary endpoints. This would result in delayed progression to Phase III studies and a push back for the timeline to approval.

So far, no vaccine developers have publicly discussed the effect that the pandemic may have on their RSV vaccine trials, whether this will mean extensions to studies, or other changes to study protocol that they will put in place. Jim Wu, the founder and CEO of Shanghai-based biotechnology company Ark Biosciences Inc., a company developing an RSV antiviral therapy, has confirmed that some of their clinical studies have been paused due to disruption from Covid-19 social distancing measures put in place by the Chinese government. Ark’s candidate is currently being investigated in a Phase II trial in hospitalized patients, but research associates were unable to travel to these hospitals. It is unclear whether the prevalence of RSV will have an impact on clinical studies for antiviral candidates, but investigators will likely need to consider exclusion/inclusion criteria for patients who have been infected with SARS-CoV-2.

Given that RSV is a seasonal virus, prevalence peaks occur in the northern and southern hemispheres at different times, and therefore trials could be affected very differently. The emergence of Covid-19 had occurred towards the end of the RSV season (October to April) for the northern hemisphere; therefore, trials run in the US and Europe will likely only see the end of their RSV season affected. Trials located in Australia and New Zealand, however, could potentially see this effect for the entirety of the 2020 RSV season. Generally, large developers will conduct RSV trials in locations in both hemispheres to take advantage of the separate RSV seasons in order to speed up development. Candidates being developed across both hemispheres could be affected more than those being developed solely in the Northern hemisphere; however, this is highly dependent on how long social distancing restrictions are enforced.

There remains enormous uncertainty surrounding estimates on how long the SARS-CoV-2 pandemic will last, which could be dependent on any successes in the development of SARS-CoV-2 therapies and vaccines. Data readouts from studies conducted over the 2019/2020 RSV season could help to determine the impact of Covid-19 social distancing on RSV development; however, it will likely be more clear following the 2020 Southern hemisphere RSV season. If the current pandemic remains for the 2020/2021 RSV season, it could mean that the development of vaccines for RSV, for which there remains a significant unmet need in pediatric, elderly, and immunocompromised populations, could potentially be delayed by years.