ResTORbio announced on Friday 15th that its current phase 3 drug trial for respiratory tract infections did not achieve its primary goal. The drug showed promise in earlier phases of testing, but sadly failed to reduce the incidence of respiratory tract infections in patients aged 65 and above.
A setback for RTB101
This news has led to the startup’s stock price plummeting to almost 82.3 percent, trading at $1.40 per share. This is perfectly understandable, as investor confidence has been shaken.
The drug, known as RTB101, is the only clinical stage drug candidate that the company currently has available, although it is developing additional drugs that target the mTOR metabolic pathway just as RTB101 does.
While the results for combating respiratory tract infections failed, the company is continuing to test the approach for other age-related diseases, most significantly Parkinson’s disease. However, the choice of Parkinson’s as the next target disease for trials has been met with skepticism by some in the industry, though, as Reuters reported, the company has made the following statement regarding these concerns:
“In the Parkinson’s disease trial, the mechanism of action will be completely different than what we were aiming for (in the respiratory illness trial),” Chief Medical Officer Joan Mannick said, adding the doses tested in the two trials were very different.
The company anticipates releasing data from the Parkinson’s trial sometime around mid 2020.
resTORbio Announces That the Phase 3 PROTECTOR 1 Trial of RTB101 in Clinically Symptomatic Respiratory Illness Did Not Meet the Primary Endpoint
BOSTON, Nov. 15, 2019 (GLOBE NEWSWIRE) — resTORbio, Inc., (Nasdaq: TORC), a clinical-stage biopharmaceutical company developing innovative medicines that target the biology of aging to prevent or treat aging-related diseases, today announced that top line data from the PROTECTOR 1 Phase 3 study, evaluating the safety and efficacy of RTB101 in preventing clinically symptomatic respiratory illness (CSRI) in adults age 65 and older, did not meet its primary endpoint, and that it has stopped the development of RTB101 in this indication. RTB101 is an oral, selective, and potent TORC1 inhibitor.
“While we are disappointed in these results, there are extensive preclinical data supporting the potential therapeutic benefit of TORC1 inhibition in multiple aging-related diseases, including Parkinson’s disease, for which we have an active Phase 1b/2a trial of RTB101 alone or in combination with sirolimus,” said Chen Schor, co-founder, president and CEO of resTORbio. “Multiple pre-clinical models have demonstrated that inhibition of TORC1 decreases protein and lipid synthesis, increases lysosomal biogenesis and stimulates the clearance of misfolded protein aggregates, such as toxic synucleins, that cause neuronal toxicity in Parkinson’s disease. We remain committed to exploring the potential benefits of TORC1 inhibition in patients, and we look forward to the data from our Parkinson’s disease trial, which we expect in mid-2020.”
The PROTECTOR 1 Phase 3 trial was a randomized, double-blind, placebo-controlled clinical trial that evaluated the safety and efficacy of RTB101 10mg given once daily for 16 weeks during winter cold and flu season to subjects 65 years of age and older, excluding current smokers and individuals with chronic obstructive pulmonary disease. The primary endpoint of the trial was the reduction in the percentage of subjects with clinically symptomatic respiratory illness, defined as illness associated with a respiratory tract infection, or RTI, based on prespecified diagnostic criteria, with or without laboratory confirmation of a pathogen. The PROTECTOR 1 trial included 1024 patients who were randomized 1:1 to receive RTB101 or placebo administered once daily for 16 weeks. In an analysis of the primary endpoint, the odds of experiencing a CSRI were 0.44 in the placebo cohort and 0.46 in the RTB101 cohort (odds ratio 1.07, p=0.65). The Company plans to conduct detailed analyses of the PROTECTOR 1 study, including additional data on safety and secondary and exploratory endpoints, which are not available at this time, with the goal of gaining insights that may explain the difference in RTB101 activity observed in PROTECTOR 1 as compared to prior Phase 2 studies.
Source: Official press release
Unfortunately, science is unpredictable, and the biology of aging is very complex. What works well in mice or even initial trial phases in humans does not always pan out, and there are often setbacks and failures along the road.
Does this mean that the approach of targeting the mTOR pathway to boost the aging immune system is not useful? Not at all, but this study does highlight the challenge we face in developing effective drugs that address aging. Our field of medicine is still in its early days, and, without a doubt, there will be more failed trials in the years to come, so while this news is disappointing, with an ever-growing number of companies and approaches arriving, we should remain optimistic that, eventually, progress will be made.