Utilization of proteomic surrogates for early detection of unexpected drug benefits
Background
Detection of benefits and adverse effects of therapies in early clinical trial phases could improve the safety, efficiency, and cost of clinical trials. For example, while SGLT2i and GLP-1 RA drugs are recognized success stories, earlier identification of their benefits beyond improved diabetic control may have had the potential to save loss of pa%ents’ lives and years of sales.
Methods
CV risk and kidney prognosis SomaSignal tests (each derived from ~5000 plasma proteins measurements using SomaScan® assay) were applied to paired plasma samples at baseline and 9-months (SUGAR-DMHF) or 1-year (EXSCEL) in intervention (EXSCEL n=1840; SUGAR-DM-HF n=45) and control (EXSCEL n=1833; SUGAR-DM-HF n=52) participants. Power calculations were performed to determine the minimum number of samples needed to detect a significant change within the treatment period with alpha = 0.05, 80% power using a t-test comparing two-sample means.
Results
We demonstrated that the cardiovascular benefits of exenatide were detectable with a proteomic surrogate within 1-year (p=0.002), with power analysis indicating a significant 1-year change is observable with group sizes of n=1368 compared with >7000 participants for up to 6.8 years follow-up. Additionally, kidney protection (p=0.037) and CV protection (p=0.06) impacts of empagliflozin within 36 weeks were detectable using proteomic surrogates in small sample sizes (n ~ 50) compared to published outcomes studies requiring thousands of participants followed for >2 years.
Conclusions
SomaSignal tests were able to predict cardiometabolic benefits of GLP-1 RA and SGLT2i drugs within a significantly shortened interval and fewer participants than in the outcome trials. Proteomics may provide a powerful tool for improving the efficacy, and cost of drug development by predicting effects of novel therapeutics in smaller, shorter studies.
Authors
Jessica Chadwick
Michael Hinterberg
Clare Paterson
Sama Shrestha
Missy Simpson
Emma Troth
Steve Williams
SomaLogic Operating Co., Inc., Boulder, CO, USA
Learn more by downloading this poster
More posters
PosterA proteomic predictor of conversion from mild cognitive impairment to dementia with potential utility in enhancing productivity of emerging clinical trials
A significant proportion of individuals with mild cognitive impairment (MCI) develop dementia, with annual conversion rates exceeding 10%. Earlier dementia diagnosis and intervention can improve outcomes, and new disease-modifying drugs are being repositioned for the preclinical stages of illness.
PosterQuantitative immunology protein panel built on the SomaScan Assay platform
The SomaScan® assay is a highly multiplexed proteomic assay that uses SOMAmer® reagents to detect proteins in various biological samples. The latest version of the SomaScan assay allows researchers to measure over 11,000 proteins in human blood. The SomaScan assay is designed to provide protein epitope abundance measurements by reporting relative SOMAmer reagent abundance quantified using DNA microarrays.
PosterComparison of Proteomic CV Risk to Established ASCVD 10-Year Risk Decision Points
The ASCVD pooled cohort equation (PCE) is well-established for CV risk assessment. Decision points for determining treatment plans are low, intermediate and high risk over 10 years, however this approach over and underestimates risk in certain subgroups. The validated CV Risk SomaSignal® Test (SST) provides 4-year risk probability of MACE allowing for timely assessment of risk, but the shorter timescale makes comparison to 10-year PCE risk less intuitive.