While conventional approaches typically rely on the statistical assessment of clinical observations, Anaxomics’ TPMS analyses clinical trial results in the context of human physiology. This novel approach unravels molecular mechanisms underlying differences in the therapeutic response to drugs, thus building a bridge between the molecular and the clinical world.
1. Systems biology changes the rules in clinical trial design and analysis
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Anaxomics’ TPMS analyses clinical trial results in the context of human physiology, tracking the deep metabolic implications instead of only assessing the statistical relevance of predefined clinical variables. This holistic approach holds the potential to generate mechanistic hypothesis for clinical observations, such as drugs failing to achieve the desired efficacy or adverse events that appear to be unrelated.
Better safe than sorry: understanding safety issues in clinical trials
There are some tragic examples of approved drugs causing serious health problems that went undetected during clinical trials. Lotronex (alosetron) was withdrawn from the market in 2000 due to serious life-threatening gastrointestinal adverse events that were initially dismissed as not associated with the drug (Moynihan R., BMJ 2002). It is often claimed that mistakes such as this one were inevitable, and probably they were at the time. Nowadays, systems biology holds the potential to anticipate and prevent these regrettable accidents.
The image below (Figure 3) shows an actual example of TPMS application in the analysis of seemingly unrelated adverse events. Distinguishing AEs caused by the drug from unrelated clinical observations or from symptoms that are expected manifestations of the illness under treatment is crucial, but also difficult. If AEs are not frequent enough, classical approaches may list them as unrelated to the treatment, leading to potential serious health issues. However, systems biology goes beyond statistical insignificance, dose-response relationships and conventional knowledge. By evaluating the effects of the drug in the protein network, TPMS pinpoints the molecular basis underlying the observed adverse events. It is, therefore, able to establish causation even when it is not directly inferable from available data.
Lotronex was reintroduced to the market, restricted only to women with severe diarrhea-predominant irritable bowel syndrome (IBS). This is a fine example of patient stratification for decreased safety issues, though it came too late.
Thanks to Anaxomics and systems biology, you can now anticipate and solve serious safety issues before they occur in your trial or, even worse, in medical scenarios. We have developed strategies for patient stratification and monitoring in accordance to their unique metabolic profile, thereby improving the trial outcome.
Optimizing efficacy to maximize the chances of success
Although safety issues are a major public concern, insufficient efficacy is actually the main reason for attrition in clinical trials, accounting for nearly the 50% of the failures between 2011 and 2012 (Arrowsmith J, Nat Rev Drug Discov. 2013). Sometimes, a drug may be effective on average, but when compared to the standard of care (SoC) might fail to deliver significant improvement. In such situation, the new medicinal product has no place in the market, unless it displays a significantly better safety profile.
A classical example of this phenomenon is that of Iressa (gefitinb), a tyrosine kinase inhibitor for lung cancer that saw restricted its use after failing to significantly extend the life of cancer patients in a confirmatory trial following its approval. In that case, posterior studies showed that the drug was actually efficacious in a subset of patients, opening the door to a second chance. This phenomenon is quite common, but unfortunately tends to go unnoticed.
Nevertheless, TPMS technology has the potential to turn a failed clinical trial into a successful one by suggesting population subsets where the drug would be more effective than average or safety issues would be reduced. TPMS identifies a subpopulation where the drug is expected to be more effective on a mechanistic basis, thereby generating market value.
Links to more detailed information about the technology applied:
Living beings under systems biology perspective
TPMS models human population variability
Combinating drugs for improving efficacy and/or safety
2. Molecular biology solutions clinical trials
Anaxomics offers a wide catalogue of services to address common issues that arise in the clinical stages of drug development:
Applying TPMS to your clinical trial
TPMS can help you to gain understanding on your clinical results and optimize the design of future trials. In order to do so, we need you to provide us with the following information:
Anaxomics proprietary technology incorporates all sorts of data into mathematical models, including any of the following: