In a second, phase I, study novel pharmacodynamic markers for Enzon Pharmaceuticals Inc’s survivin messenger ribonucleic acid (mRNA) antagonist were identified from hair follicle analysis.
The first study was completed successfully in 12 healthy normal volunteer elderly men and involved collection of plucked eyebrow and scalp hair. Dr Ged Brady will present data which demonstrates plucked human scalp hairs as a preferred method for assessing androgen receptor directed therapies. Quantitative PCR analysis identified a panel of 7 genes which were reliably expressed in most scalp hairs. This gene panel could be used to monitor drug induced gene expression change for compounds targeting the androgen receptor pathway, whilst using single plucked hair as a non invasive surrogate tissue.
In the second, Phase I dose escalation, study in cancer patients for Enzon Pharmaceutical Inc’s compound EZN-3042 (a novel survivin messenger ribonucleic acid (mRNA) antagonist) hair follicle analysis was used to identify novel pharmacodynamic markers to support dose scheduling decisions.
Epistem has previously presented data on the use of GenetRx™ technology to monitor the effects of a range of different classes of drugs including: erlotinib, an epidermal growth factor receptor inhibitor; gemcitabine, commonly known as Gemzar and a c-Met inhibitor. These positive new data confirm the clinical utility of GenetRx™ to monitor drug induced changes in epithelial tissue. Epistem is active in collaborations with partners developing compounds which modulate the Notch, c-Met and Hedgehog signalling pathways.
“We are extremely pleased that our technology is sufficiently sensitive to identify a panel of genes applicable for further clinical investigation using plucked hair. We are encouraged that we were able to identify a robust gene set with low variability by generating a large sample set from just 3 individual scalp hairs per timepoint per subject.” said Lydia Meyer-Turkson, Vice President of the Biomarker Division at Epistem plc. “In addition, the survivin antagonist data validates our technology for antisense molecules in the clinic. Data from these studies strongly supports the case for plucked hair as a valuable surrogate tissue with broad utility to measure transcriptional changes and as a readout for pharmacodynamic response, for a range of oncology therapies”