Boston-based resTORbio, which was spun out of Novartis in April 2017, announced positive topline results from its Phase IIb clinical trial of RTB101 in patients with respiratory tract infections (RTIs).
RTB101 is an oral, selective, and potent inhibitor of rapamycin complex 2 (TORC1). In the trial, it showed a statistically significant and clinically meaningful drop in the percentage of patients with one or more laboratory-confirmed RTIs during 16 weeks compared to placebo. The dosage was 10 mg per day.
Chen Schor, co-founder, president and chief executive officer of resTORbio, said in a statement, “The primary endpoint of this Phase IIb study, the percentage of patients with laboratory-confirmed RTIs, was chosen based on feedback from the FDA, and we look forward to discussing these results at our end of Phase II meeting with the agency. RTIs are the fourth leading cause of hospitalization in patients 65 years and older, and the second leading cause of hospitalization in patients 85 years and older in the U.S. We are committed to helping the millions of elderly patients at high risk of morbidity and mortality due to RTIs.”
The trial showed a 30.6 percent decrease compared to placebo in the percentage of all patients treated with the 10 mg dose of the drug daily who developed one or more lab-confirmed RTIS, and a 20.6 percent decrease relative to placebo with the 5 mg dose. There was no decrease relative to placebo in patients treated with either 10 mg of RTB101 twice daily or a combination of RTB101 10 mg and everolimus 0.1 mg once a day. According to the company, this suggests “that less TORC1 inhibition with RTB101 10 mg once daily may have greater benefit in high-risk elderly patients.”
In addition to the RTI evaluations, the company conducted a pre-specified analysis of patient subgroups. There was a 68.4 percent decrease in lab-confirmed RTIs in all asthma patients, for example, and a 66.7 percent decrease in all patients 85 years of age and older. There was also a 26.9 percent decrease in RTIs in all type 2 diabetes patients.
There was no observed decrease in RTIs in patients with COPD or current smokers. When excluding COP patients, there was a 42 percent decrease in RTIs and when excluding current smokers, there was a 43.9 percent decrease in RTIs.
The drug was generally well tolerated. All adverse events were mild or moderate except 11 that were severe in the RTB101 10 mg once daily cohort and 22 in the placebo cohort. The type of adverse events was not specified.
The trial enrolled 652 patients with increased risk of morbidity and mortality from RTIs, including patients 85 years or older, 65 years or older with asthma, type 2 diabetes, COPD or current smokers. There were two parts to the trial. Part 1 was run during the winter cold and flu season in the southern hemisphere and 179 elderly patients were randomized to take either placebo, RTB101 5 mg or RTB101 10 mg once daily. An interim analysis was conducted by an unblended data monitoring committee at that time, who chose the RTB101 10 mg dose to move into Part 2 of the trial.
Part 2 was held during the winter cold and flu season in the northern hemisphere and 473 elderly patients were randomized to receive either placebo, RTB101 10mg once a day, RTB101 10 mg twice a day, or RTB101 10 mg in combination with everolimus 0.1 mg once a day. They were treated with the drug for 16 weeks, then followed for an additional eight weeks.
“This Phase IIb has successfully defined a dose, RTB101 10 mg once daily, to be evaluated in future pivotal studies,” said Joan Mannick, resTORbio’s co-founder and chief medical officer, in a statement. “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 IIb study. We have also identified patient populations that were particularly high responders. 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. We look forward to working closely with the U.S. Food and Drug Administration (FDA) and other regulatory agencies on this program.”
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