Positive topline results have been announced from the phase 2b clinical trial that evaluated an appropriate dose range for RTB101 and demonstrated statistically significant reductions in the incidence of respiratory tract infections.
“This phase 2b has successfully defined a dose, RTB101 10 mg once daily, to be evaluated in future pivotal studies,” Joan Mannick, MD, cofounder and chief medical officer of resTORbio, said in a press release. “That dose led to a statistically significant decrease in the incidence of laboratory-confirmed RTIs and was well-tolerated in the high-risk elderly patients enrolled in the phase 2b study.”
According to the release, the randomized, double-blind, placebo-controlled clinical trial enrolled 652 patients at an increased risk for morbidity and mortality from respiratory tract infections (RTI). Patients included in the study were either aged 85 years and older or were aged 65 years or older and had asthma, type 2 diabetes mellitus, chronic obstructive pulmonary disease or were current smokers. The different dosing methods of RTB101 — an oral compound inhibitor of target of rapamycin complex1 (TORC1) — were reviewed in two regions and the study was broken down into two parts with a 16-week treatment period.
Researchers investigated a dose range of 5 mg and 10 mg once-daily dosing during the first part of the trial, which was conducted in the winter cold and flu season in the southern hemisphere. The second part of the clinical trial was conducted in the same season but in the northern hemisphere and investigated a dose range of 10 mg once daily and twice daily, as well as a once daily combination of 10 mg of RTB101 and 0.1 mg of everolimus.
Compared with placebo, the incidence of one or more laboratory-confirmed RTIs was reduced by 20.6% in all patients treated with RTB101 5 mg daily (P = .018). A “statistically significant and clinically meaningful” 30.6% reduction was observed in all patients treated once daily with RTB101 10 mg (P = .026), according to the company. However, the percentage of patients with one or more laboratory-confirmed RTIs was not reduced when treated with RTB101 10 mg twice daily or the combination of 10 mg of RTB101 and 0.1 mg of everolimus once daily. resTORbio suggested that in high-risk elderly patients, less TORC1 inhibition with RTB101 10 mg once daily may be more beneficial.
The study also conducted a prespecified analysis of patient subgroups and compared the RTB101 10 mg once daily cohort with the placebo cohort. In all asthma patients, a 68.4% decline in RTIs was observed. Additionally, all patients aged 85 years and older and all patients with type 2 diabetes had an RTI incidence reduction rate of 66.7% and 26.9%, respectively. No incidence reduction was found in patients with chronic obstructive pulmonary disease or in those who were current smokers, according to the study. However, when patients with chronic obstructive pulmonary disease were excluded, a 42% decrease in RTI incidence was reported (P =.002) for all patients and a 43.9% reduction was observed in all patients when current smokers were excluded (P = .001).
RTB101 with a dosing range of 10 mg once was found to be well-tolerated, and resTORbio looks to further study the compound as a preventive treatment for RTIs in high-risk populations.
“We believe the findings of this trial provide us with a clear path forward for pursuing a pivotal program for RTB101 to reduce the incidence of RTIs in high-risk elderly patients,” Mannick added. “We look forward to working closely with the FDA and other regulatory agencies on this program.”
Disclosure: Mannick founded and currently works for resTORbio.