Table of Contents
- 1 Platform for microbial biomarker discovery
- 2 Research initiatives and collaborations
- 3 How can insight into the gut microbiome improve the success rate of your clinical trial?
Components of the microbiome, such as specific bacteria or bacterial enzymes, hold great potential as predictive biomarkers. So far, this reservoir is largely unusable for pharmaceutical and clinical development, despite the increasing understanding of the microbe’s effect on drug metabolism.
Varying drug response between patients is a dangerous and expensive challenge in the clinic due to significant treatment delays and adverse effects. Personalized medicine holds the promise to tackle these issues by incorporating companion diagnostics guided by predictive biomarkers in standard clinical practice.
Beyond causing extensive issues in the clinic, varying drug response is also a challenge in the development of new drugs as it can significantly affect the results of a clinical trial.
“To date, microbial strains and enzymes have been experimentally demonstrated to directly or indirectly impact the metabolism and efficacy of over 50 therapeutic drugs, driving inter-patient variability in drug activation, inactivation and toxicity” (Guthrie and Kelly, 2019)
Platform for microbial biomarker discovery
At BIOMCARE we are contributing to this progress and have developed a prototype for A-Z microbial biomarker discovery. The platform builds on our established microbiome sequencing and analysis service, which supports an easy workflow from sample collection to the final statistical analysis. The analysis results in a list of ranked predictive biomarkers and estimation of the predictive ability of the identified markers, as univariate or multivariate predictors.
We are participating in the large NORDIC-SUN clinical trial by utilizing our already established infrastructure and with the aim to validate the robustness of our ensemble based statistical solution.
[Illustration] Shift in gut microbiome between drug responders and non responders
Research initiatives and collaborations
BIOMCARE actively supports and engages in research initiatives that bring the value of the microbiome closer to the clinic. We are always open for discussions of possible collaborations and to make our microbiome expertise available for research initiatives.
If you are planning or currently undertaking a clinical trial of a compound that might be influenced by the gut microbiome, we would like to hear from you. Such a drug is likely orally ingested, might depend on or effect the physiological structures, cells, metabolites or hormones that are linked to the gut microbiome. Alternatively, the drug might be known to have variable drug response not explained by human genetics.
If you decide to collaborate with BiomCare we only need two things from you during the trial:
- A stool sample from each study participant before the drug is administered. BiomCare provides you with a stool collection kit that includes all instructions and an envelope with return address. This facilitate at-home stool collection, which reduces the logistic challenges for the clinic and allow the participants to follow their usual toiled routines.
- Clinical data on the observed drug response, together with a few additional phenotypic variables such as age, gender and BMI. The data must have an ID that can link the clinical data with the stool samples. BiomCare does not otherwise need person-identifying information.
How can insight into the gut microbiome improve the success rate of your clinical trial?
Analysis of the gut microbiome is increasingly becoming a part of clinical testing of pharmacological products, and for good reason: The human microbiome is personal – with high diversity between people and reasonably high stability within a person over time – and highly involved in drug metabolism.
By analyzing the gut microbiome profile of patients in the trial, BiomCare can assess:
- How important is the gut microbiome for drug response?
- Identify microbial biomarkers
- Calculate how well the biomarkers predict drug response (e.g. separate high, low or non-responders)
By incorporating the results from BiomCare’s analysis into your trial statistical analysis, you can learn if the microbiome is a key driver of varying drug response and how it influences your efficacy profile.
By statistically stratifying participants retrospectively into high and low responders using the multimarker model developed by BiomCare, you learn if efficacy is dependent on microbiome profiles. This can improve your power and confidence in your results and provide further understanding of physiological drug mechanisms.
Altogether, incorporating the gut microbiome analysis into your clinical trial holds the potential of increased control and reduced risk due to varying drug response. Identification of predictive biomarkers can further facilitate co-development of companion diagnostics and improve the competitive abilities of your drug on the market.
1) Doherty et al, 2017; Guthrie et al, 2017; Ananthakrishnan et al., 2017; Zimmermann et al., 2019
[Illustration/Graph] Accuracy of biomarker predictions for classification of patients – based on drug response
We used BIOMCARE to analyse paired human faecal samples from a clinical trial. … I can strongly recommend the company.