Can RTB101 Decrease RTIs Due to Multiple Viruses in Older Adults?

Respiratory tract infections (RTIs) are a serious threat to older adults as they are a leading cause of hospitalization and death. These infections can be difficult to treat as they are caused by multiple viruses, some of which do not have effective treatments.

Investigators have hypothesized that an immunotherapy which enhances pan-antiviral innate immunity may be able to reduce the incidence of RTIs in adults over the age of 65 years.

In a mouse model, inhibition of targets downstream of target of rapamycin complex 1 (TORC1) was found to upregulate pan-antiviral gene expression and protect the mice from viral RTIs.

A team of investigators set out to evaluate whether TORC1 inhibition could increase antiviral gene expression and decrease the incidence of RTIs in older human adults. Their findings were presented in a late breaking oral abstract session at IDWeek 2019.

Contagion® spoke to lead presenter Joan Mannick, MD, chief medical officer of resTORbio, regarding the research.

The research team conducted a double-blind, placebo-controlled study assessing the effect of the TORC1 inhibitor RTB101 alone or in combination with the TORC1 inhibitor everolimus on reducing the incidence of RTIs. A total of 652 participants were enrolled into the study.

The participants included older adults at an increased risk of RTI-related morbidity and mortality, factors of which include being either at least 85 years of age or being 65 years of age with comorbidities such as asthma, COPD, type 2 diabetes mellitus, or a current smoker.

Mannick also discussed the findings of the research and the future of RTB101.

The participants were treated with either oral RTB101 5mg or 10mg once daily (QD), RTB101 10mg twice daily, RTB101 10mg + everolimus 0.1mg QD, or matched placebo for 16 weeks during cold and flu season. The primary endpoint of this study was the percentage of subjects with at least 1 laboratory-confirmed RTI through Week 16.

In the intent-to-treat analysis, a once daily 10mg dose of RTB101was found to reduce the percentage of RTIs by 30.6% compared to placebo (p = 0.025). RTB101 10mg also reportedly reduced the incidence of RTIs caused by multiple different viruses and upregulate interferon-stimulated pan-antiviral gene expression in the whole blood (p = 0.00001 vs. placebo).

Overall, the daily 10mg dose reduced the time to alleviation of moderate to severe RTI symptoms by 5 days, reduced the rate of all-cause hospitalization (rate ratio 0.439, 90% CI 0.196-0.983, p = 0.047).

“RTB101 10mg QD was associated with a significant reduction in laboratory-confirmed RTIs due to multiple viral pathogens that lack effective medicines for treatment or prevention,” the authors concluded. “RTB101 was observed to upregulate interferon-stimulated pan-antiviral gene expression, which may underlie the reduction in RTI incidence.”

The abstract, “TORC1 Inhibition with RTB101 as a Potential Pan-Antiviral Immunotherapy to Decrease the Incidence of Respiratory Tract Infections Due to Multiple Respiratory Viruses in Older Adults,” was presented in a late breaking oral abstract session on Thursday, October 3, 2019 in Washington, DC.