Along with other respiratory infections, respiratory syncytial virus (RSV) was heavily suppressed during its regular season due to lockdown measures implemented during the ongoing pandemic. With waning immunity levels and less social distancing, RSV has now re-emerged, adding more pressure on healthcare systems. A record-breaking 563 new RSV cases were reported in the past week in the US during this atypical summer season. The Centers for Disease Control and Prevention (CDC) has issued a health advisory and trends indicate that the peak is yet to come.
RSV is a winter virus and cases are rarely observed during the summer; however, this surge was not unexpected based on similar situations in Australia and New Zealand, where the summer season occurs earlier than in the US and can give insights into what to expect for seasonal pathogens. Following this reported dramatic increase in RSV cases, healthcare professionals now should be testing SARS-CoV-2-negative patients with respiratory symptoms for RSV to prevent further complications and deaths.
Interest in RSV vaccines and prophylaxis has been largely overshadowed by the ongoing COVID-19 pandemic. Very few cases were seen in the winter of 2020, compared to the normal annual case count, largely due to implementation of mask wearing and social distancing measures. This had the unexpected consequence of reducing the number of patients eligible for enrollment for RSV studies. With the prevalence of cases today, companies are now able to resume trials in a hotly contested race to bring improved therapies and the first-ever vaccines to market.
While the awareness of RSV in the general population remains low, pharmaceutical companies are still working rapidly to provide the FDA with pivotal trial data to submit their vaccines and prophylactic treatments for approval. It is clear that vaccines are a much-needed weapon to tackle RSV; however, a new monoclonal antibody, nirsevimab, developed by AstraZeneca and Sanofi, has demonstrated major advantages in clinical trials involving infants over the current standard of care, Synagis (palivizumab).
Nirsevimab (MEDI8897) has an extended half-life of up to 117 days, compared to the 20-day half-life of Synagis. A single dose can provide protection for at least five months, which covers an entire RSV season. Further, Synagis has a hefty price tag of up to $9,000 per year, providing an opportunity for price competition. Synagis is limited to use in high-risk premature infants, while nirsevimab is intended to be used in all infants.
The Phase II/III MELODY trial (NCT03979313) investigating nirsevimab met its primary endpoint and these data will be part of nirsevimab’s regulatory submission targeted for early 2022. Additionally, results from the Phase II/III MEDLEY trial (NCT03959488) comparing nirsevimab to Synagis in infants, and a Phase IIb study, will also be part of the FDA approval package. While complete MELODY results are pending, nirsevimab reduced the incidence of medically attended lower respiratory tract infections (LRTI) due to RSV compared to placebo in healthy late-preterm and term infants during their first RSV season. With FDA breakthrough designation and positive Phase III results, it is on track to become the first new intervention approved for RSV in 23 years.
The latest generation of vaccine candidates in late-stage development uses an improved ‘pre-fusion’ RSV F-protein antigen that has been associated with increased efficacy over the earlier ‘post-fusion’ conformations. Currently, GlaxoSmithKline is on track to bring the first older adult RSV vaccine to market, and Johnson & Johnson the first infant vaccine, while Pfizer is closest to a maternal vaccine approval. Until new interventions enter the market, it remains important to use Synagis in high-risk infants to prevent contracting the disease and associated healthcare costs.