- Shares of resTORbio shot up 120% Wednesday morning as the Boston-based drugmaker unveiled what it deemed positive clinical data on an investigational therapy for respiratory tract infections (RTIs). Some weren't so convinced, and suggested the company shaped the results to make the therapy look better than it is.
- The data come from a two-part Phase 2b study testing resTORbio's RTB101 in elderly patients who are at greater risk of disease or death from RTIs. After 16 weeks, the share of patients who got a laboratory-confirmed RTI was 30.6% lower for those taking 10 mg of the drug once a day compared to those on placebo.
- That 30.6% figure, however, combines patients from both parts of the study — which were conducted in the southern and northern hemispheres, respectively, during their winter cold and flu seasons. What's more, data from Part 2 showed the share of patients contracting RTIs was actually higher when they were treated twice daily with 10 mg RTB101 compared to placebo.
Investors and some analysts may be rejoicing at resTORbio's latest data, but the biotech still has some explaining to do. On dosing, for example, there remain questions about why patients seemed to significantly benefit from the 10 mg, once-daily dose and not at all from the 10 mg, twice-daily dose.
RTB101 inhibits a protein synthesis pathway called target of rapamycin complex 1, or TORC1. Company executives reasoned the TORC1 inhibition that comes with a twice-daily regimen may be too much for high-risk elderly patients, and are therefore advancing just the once-daily regimen into pivotal testing.
Yet, resTORbio also evaluated a 5 mg once-daily dose of the drug in Part 1 of the Phase 2b study, and found it didn't significantly outperform placebo in reducing the percentage of patients with one or more laboratory-confirmed RTIs. It's possible the 10 mg once-daily option is a Goldilocks of sorts, but something investors could press for more details on as RTB101 advances through the clinic.
Another concern is how the biotech pooled results from Parts 1 and 2 for the topline analysis. On a July 25 call with investors, resTORbio's Chief Medical Officer Joan Mannick said the drug didn't outperform placebo on Part 2 alone, so they combined it with Part 1 to make the number of patients studied larger. After that move, the trial hit statistical significance.
Critics also pointed out other factors, such as the use of a statistical measures like a 90% confidence interval and one-sided p-value — which is used in clinical trials to measure a drug's efficacy against a comparator — in their evaluation of resTORbio's data.
Based on the trial results and subgroup assessments, resTORbio expects to further study its drug in patients 65 years and older who are non-smokers or have asthma, and in patients 85 years and older. While the company has also investigated RTB101 in combination with everolimus, the active ingredient in several brand name drugs, including Novartis' cancer therapy Afinitor, the data suggest it works best in healthier elderly patients, and therefore won't be studied in resTORbio's pivotal trials.