Shionogi's Oral Antiviral S-337395 Shows Promise in Phase 2 RSV Human Challenge Trial
Key Insights
Shionogi (search)'s investigational oral antiviral S-337395 significantly reduced viral load in a Phase 2 human challenge trial for Respiratory Syncytial Virus (search) (RSV (search)).
The highest dose group of S-337395 demonstrated an 88.94% reduction in viral load compared to the placebo group (P<0.0001), along with improved clinical symptom scores.
S-337395 was generally safe and well-tolerated, with no serious adverse events reported during the randomized, double-blind, placebo-controlled study.
Shionogi (search) & Co., Ltd. has announced positive results from a Phase 2a human challenge trial of its investigational oral antiviral candidate, S-337395, for Respiratory Syncytial Virus (search) (RSV (search)). The trial, conducted by hVIVO, demonstrated a statistically significant reduction in viral load in healthy adult volunteers infected with RSV.
The randomized, placebo-controlled, double-blind study evaluated the efficacy and safety of S-337395, administered orally once daily for five days. The primary endpoint, reduction in viral load, was met with significant results. In the highest dose group, an 88.94% reduction in viral load was observed compared to the placebo group (P<0.0001). Furthermore, participants in this group experienced a statistically significant improvement in clinical symptom scores.
Safety and Tolerability
S-337395 demonstrated a favorable safety profile in the trial. No serious or severe adverse events were reported, and there was no dose-dependent increase in the incidence or severity of adverse events. No participants discontinued the study due to adverse events.
Mechanism of Action
S-337395 is designed to inhibit the activity of the RSV (search) L protein (search), which is essential for viral replication. This mechanism of action differs from F protein inhibitors, potentially offering higher efficacy and a more rapid reduction in viral load by preventing viral proliferation within infected cells.
The Need for New RSV Treatments
RSV (search) is a common respiratory virus that can cause severe illness, particularly in young children and older adults. In the U.S. alone, RSV leads to approximately 2.1 million outpatient visits and 58,000 to 80,000 hospitalizations among children under 5 years old annually. Among adults 60 years and older, RSV results in approximately 0.63 million to 2.3 million outpatient visits and 70,555 to 168,130 hospitalizations each year. Effective antiviral treatment options for RSV are limited, highlighting the significant unmet medical need.
Trial Design and Demographics
The Phase 2 human challenge trial involved 114 healthy adults who were actively inoculated with RSV (search). Participants were randomized to receive either S-337395 or a placebo for five days. The primary endpoint was the area under the curve (AUC) of the viral load over time.
Implications and Future Directions
These positive Phase 2 results support the continued development of S-337395 as a potential oral treatment for RSV (search) infection. Shionogi (search) is committed to advancing the clinical development of S-337395, which has received Fast Track designation from the U.S. Food and Drug Administration (FDA), in collaboration with UBE Corporation (search).