resTORbio surges as midstage data set up phase 3 for drug to prevent RTIs in the elderly

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There are 24 million elderly patients in the U.S. who are at risk of mortality and morbidity from RTIs. (Getty/Rawpixel)

Armed with positive phase 2b data, resTORbio is hoping to start pivotal trials next year for its lead drug to prevent respiratory tract infections (RTIs) in the elderly.

And with proof-of-concept for TORC1 (rapamycin complex 1) inhibitor RTB101 in the bag, the Boston biotech will accelerate plans to test the drug in other diseases associated with aging, including Parkinson’s disease, according to its chief medical officer, Joan Mannick, M.D.

Shares in resTORbio, which made its Nasdaq debut just a few months ago, rocketed 69% premarket on the news.


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Older people are more prone to infections as immune function declines with age, and resTORbio is hoping that RTB101 could be given prophylactically for a four-month period during the cold and flu season to people at risk of mortality or morbidity due to RTIs.

The Novartis spinout now has hard data to support that idea. Top-line results released today from a phase 2b dose-ranging study of RTB101, given daily to patients aged 65 or more over 16 weeks, showed a statistically significant 30.6% reduction in the proportion who developed a confirmed RTI.

The benefits were even greater among two particularly high-risk subgroups. In people over 85, the proportion developing an RTI fell by two-thirds, 66.7%, with a similar 68.4% reduction among over-65s who also had asthma. Mannick said the company will be presenting results to the FDA and other regulators to “obtain feedback on the design of our phase 3 program that we expect to initiate in 2019.”

There seemed to be no additional benefit when RTB101 was combined with Novartis’ mTOR inhibitor Afinitor (everolimus), which is approved as a treatment for cancer. ResTORbio suggested less is more when it comes to TORC1 inhibition in this setting. RTB101 also wasn’t as effective in subjects who had chronic obstructive pulmonary disease (COPD) or who were current smokers.

Mannick told us that when set up, the trial was 80% powered to detect a 40% reduction compared to placebo in the percent of patients with one or more laboratory-confirmed RTIs.

“We enrolled more patients than was originally planned when we made our powering assumptions. Therefore, we observed a statistically significant 30.6% reduction in the percent of subjects with laboratory-confirmed RTIs in the RTB101 10 mg once daily cohort.”

That is the dose that will be taken forward into phase 3. Meanwhile, the patients enrolled in the Phase 2b trial will be followed for an additional eight weeks off study to see if the reduction in the incidence of RTIs persists after study drug discontinuation, and those results should be announced later in 2018.

The company will be treading new ground with a drug designed for preventative use for RTIs, but Mannick is confident that resTORbio will be able to make a solid case for RTB101 with Medicare and other payers if it wins approval.

“There are 24 million elderly patients in the U.S. who are at risk of mortality and morbidity from RTIs and an estimated 75M in the U.S., major European countries and Japan combined,” she pointed out. Moreover, RTIs are the fourth leading cause of hospitalizations and the seventh leading cause of death in people over age 65, as well as the second top cause of death among those over 85.

Inhibition of TORC1 has been shown to enhance immune, cardiac and neurologic functions, suggesting potential benefits in several aging-related diseases, and along with RTIs, resTORbio is also looking at RTB101’s potential in preventing urinary tract infections and heart failure.

The recent IPO has left resTORbio with cash reserves of around $135 million, which Mannick said is enough to fund two pivotal trials of RTB101 as well as two proof-of-concept studies in additional indications, and keep the company going through a possible submission for its lead drug in 2020.

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