Recently, Unity Biotechnology completed a phase 1 trial of its drug UBX0101. While the trial found that the drug was non-toxic and lacked serious side effects, many of its results were not statistically significant.
UBX0101 aims to treat osteoarthritis and possibly other diseases of aging through directly targeting one of the aspects of aging itself. The drug destroys senescent cells, which are one of the hallmarks of aging. Since aging is one of the major risk factors for many diseases and disabilities, it is possible that using drugs to target the hallmarks of aging could slow or even reverse aging and its associated diseases, improving both healthspan (the portion of life spent in good health) and lifespan.
The trial found that, at the dosages of the drug tested, there were no serious side effects. This is the most important point of the whole study: with low numbers of patients tested (14 people were given a placebo, 16 people were given a low dose, and 18 people were given a supposedly effective high dose), a phase 1 study does not generally have the power to detect the effectiveness of a drug.
Tests on the fluid within the knees of high-dose patients indirectly gave evidence to support the suggestion that the drug was able to destroy senescent cells to a significant degree and reduce the inflammatory signaling molecules that are secreted by these cells. On a theoretical level, this is good news, showing that the drug works as intended.
There were two tests done to gain an idea of how effective the drug is at these dosages: analyzing the pain felt by subjects to see if the drug gave any pain relief and checking for a change in the WOMAC scale , which is used to determine the symptoms and disability associated with osteoarthritis.
It was found that high doses of the drug provided statistically significant decreases in self-reported pain on a 0-10 scale when compared to placebo, meaning that there was a high probability that this was not due to random chance.
When WOMAC-A was used to determine if the drug had an impact on pain, the drug seemed to have an effect, but it did not rise to the level of statistical significance; however, this may be expected due to the low number of patients, even if the drug works. WOMAC-C was used to determine if the drug had an impact on function, and it did not find any significant effect either; MRIs were used to detect inflammation and found no significant change. This is concerning, and it is something that the company may have to address moving forwards, either by having more participants in its trials or using higher dosages of the drug.
At this point, there are two main options for Unity: either repeat the phase 1 trial on a higher dose in order to hopefully get a stronger effect or proceed to a phase 2 trial, hoping that more subjects would allow the test to detect a significant effect that a smaller trial would overlook.
It is possible that the company may prefer the second strategy – to go to a phase 2 trial – since a cohort that the company added to the trial partway through was composed of patients who took the same high dose as a subset of the previous cohort, and their choice of this specific high dose was informed by a model suggesting that a dose 4 times lower than the highest dose may have an effect on the disease.
The company has stated that it will release additional data relevant to this study in an upcoming meeting, and, yesterday, it hosted a conference call to discuss the data.
Overall, this trial has given promising results, though it isn’t perfect. The main focus of this Phase 1 trial was on toxicity, and the results showed a lack of toxicity. The impact on senescent cells was expected and promising, as was a statistically significant decrease in subjective pain.
It is hard to draw conclusions now; the dose could be too low, or the drug could be ineffective. Either way, with a lack of toxicity, further trials on the drug remain promising, either with plans to detect the maximum tolerated dose in a second phase 1 trial or to increase the power of the analysis in a larger phase 2 trial. We will be following this story closely as it develops.
 Salaffi, F., Leardini, G., Canesi, B., Mannoni, A., Fioravanti, A., Caporali, R. O., … & Punzi, L. (2003). Reliability and validity of the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index in Italian patients with osteoarthritis of the knee. Osteoarthritis and cartilage, 11(8), 551-560.