Molecular Markers to Assess Drug Utility and Efficacy

Unlike general diagnostic assays, which confirm or determine the presence of disease, a companion diagnostic is defined as a FDA-approved in vitro diagnostic (IVD) test for a biomarker used to identify patients who will be most likely to receive benefit from a specific therapeutic. This category of biomarkers can also be utilized for detection of patients at risk for adverse events, individualizing dosing, monitoring drug levels and analyzing response.

In 2014 the FDA published guidelines for drug discovery and pharmaceutical companies to establish the utility of in vitro companion diagnostics in early stage drug development, and recently guidelines were proposed to encourage the co-development of a therapeutic products and accompanying companion diagnostics. IVD assays often target genes, microRNAs, and proteins that are relevant to a particular therapeutic, and the development of an IVD test often employs the open-ended transcriptomic, genomic, and protein investigations.

An example of a companion diagnostic based RNA sequencing technology is the FoundationFocusTM CDxBRCA test which aids in the identification of ovarian cancer patients for which Clovis Oncology’s RubracaTM (rucaparib) will be most efficacious. This assay detects sequence alterations in BRCA1 and BRCA2 (BRCA1/2) genes using formalin-fixed paraffin-embedded (FFPE) ovarian tumor tissues. Similarly, to determine if ovarian cancer patients are eligible for treatment with AztraZeneca’s LynparzaTM (olparib), the BRACAnalysis CDxTM was developed to detect deleterious or suspected deleterious germline BRCA variants. Myriad Genetic Laboratories, Inc. designed this assay to identify variants in the protein coding regions and intron/exon boundaries of the BRCA1 and BRCA2 genes in whole blood samples.

Melanoma, the most dangerous form of skin cancer caused by genetic mutations to skin cells, can be treated with Genetech’s Zelboraf (vemurafenib) or Novartis’ combination therapy of Mekinist (tramatenib) and Tafinlar (dabrafenib). Companion diagnostic assays exist with both treatment options to ensure patients possess the correct genotype in order for the therapeutics to provide maximum effect. Roche Molecular Systems, Inc manufactures the Cobas 4800 BRAF V600 Mutation Test to be used in conjunction with Mekinist, while the THxIDTM BRAF Kit is produced by bioMérieux Inc. to test for BRAF V600E and V600K mutations in FFPE melanoma samples.

ORB Platforms Available for Companion Diagnostic Discovery and Development

ORB is an experienced service provider of RNA sequencing, metatranscriptomic analyses, and immunoassay studies designed to support analysis of pre-clinical samples as well as research studies of samples from completed clinical trials. ORB’s established and flexible bioinformatic pipelines, as well as post-project support, enable researchers to identify markers relevant to specific treatments and move forward with confidence.

ORB biomarker discovery services can shorten your development time of companion diagnostics & drug therapies:
  • Biofluid Profiling ORB provides analysis of over 7 biomolecules within biological fluids: exosomes, mRNA, lncRNA, small RNA, oncogenes, cfDNA methylation, and proteins. Pilot studies are conducted where possible to minimize consumption of precious and limited clinical samples. Scientists at ORB are highly experienced in working with a wide variety of circulating, excreted, and secreted biofluids.
  • Exosomal RNA profiling Interrogate unique circulating disease- or therapeutic treatment-related markers in exosomes as well as tissue or cell specific exosomal RNA markers.
  • RNA sequencing Identify mutations, which impact treatment efficacy in FFPE or biofluid samples using the Illumina NextSeq 500, HiSeq 2500 and HiSeq 4000 instruments.
  • Metatranscriptomics Detect microorganisms and their metabolic signatures associated with treatment effects by sequencing of whole metatranscriptomes from a variety of biospecimens.
  • MicroRNA ORB offers microRNA microarray services with Affymetrix industry standard arrays, as well as proprietary arrays and labeling/ hybridization processes to provide unparalleled detection of low abundance target RNA molecules. ORB's microRNA profiling services are optimized to support biomarker discovery initiatives.
  • Immunoassays A complete service for the accurate and sensitive quantification of proteins in a wide variety of samples. Custom panels can be designed to evaluate 1 to 60 analytes in several disease areas.  Oncology related analytes include circulating tumor, angiogenesis, and metastasis biomarkers.
  • cfDNA Bisulfite Sequencing Explore disease or treatment-effect on methylation patterns using tissue, genomic DNA (gDNA), or circulation cell-free DNA (cfDNA) samples.
  • Oncopanels Analyze liquid biopsy samples using high coverage sequencing of the protein coding region of up to 100 genes with known cancer association. Panels detect genetic variants with allelic frequencies as low as 1% and assay multiple variant types such as germline and somatic mutations, gene fusion events, INDELs, SNPs, and structural variations.
  • Predictive Modeling Identify reliable genetic biomarkers that may be relevant for diagnostic, prognostic or screening purposes.

All services provided by ORB are supported with post-project consultations and generation of materials for patent and FDA applications, manuscripts, and posters. ORB companion diagnostic-focused services are designed to reduce attrition and reduce the time from compounds’ discovery to approval.

Sample Types
(platform-specific analysis available)

  • Whole Blood
  • Serum
  • Plasma
  • Tissues
  • Exosomes
  • Cell-free DNA
  • Genomic DNA
  • Cells
  • Stool
  • Urine
  • Cerebrospinal Fluid
  • FFPE
  • Lymphatic Fluid
  • Ascites Fluid
  • Synovial Fluid
  • Milk
  • Lavage
  • Buccal Swabs
  • Dried Blood Spots
  • Tears

Contact us to learn more about ORB’s companion diagnostic development programs!