C4X Discovery Holdings Limited has announced the discovery of a genetic response signature capable of differentiating between patients with ulcerative colitis who respond to the α4β7 integrin antibody vedolizumab and those who do not. This advancement, stemming from C4XD's PatientSeek platform, represents a significant step toward precision medicine in inflammatory bowel disease (IBD).
Genetic Signature for Patient Selection
The PatientSeek platform employs a unique mathematical approach to analyze patient genetic records alongside other data, such as electronic health records. This analysis has revealed a statistically significant predictive 'genetic response signature' based on genetic variation in the non-coding regions of DNA. Unlike clinical and omic biomarkers, genetic signatures remain constant over time and are independent of disease progression, offering a stable marker for patient selection.
Clinical Implications and Future Applications
The identification of this genetic signature holds promise for improving the efficiency and success rates of clinical trials. By identifying patients most likely to respond to vedolizumab, future trials can be smaller and more targeted. C4XD intends to leverage this predictive power in clinical trials for its own small molecule α4β7 integrin program and apply this precision approach across its pipeline, including TNFα and PAD4 programs.
Vedolizumab and the α4β7 Integrin Target
Vedolizumab, an α4β7 integrin antibody, is a commonly used therapy for ulcerative colitis. However, not all patients respond to the treatment. The ability to predict which patients will benefit from vedolizumab represents a major advancement in the treatment of IBD. Currently, no validated biomarker exists to predict response to advanced therapies in IBD, leaving a significant unmet need in guiding clinical practice.
C4XD's Perspective
Clive Dix, Executive Chairman of C4XD, emphasized the importance of this discovery, stating, "Until now, no currently available biomarker has been robustly validated in predicting response to individual advanced therapies to guide clinical practice for IBD, leaving many patients underserved. Utilizing our PatientSeek platform we have now identified a genetic response signature that separates responders and non-responders to vedolizumab... This is an incredibly exciting first for immuno-inflammation precision medicine as these data clearly demonstrate the power of PatientSeek’s analytical capabilities for patient selection based solely on genetic data."
