Companion Dx Quandary
Companion diagnostics are assays that evaluate proteins or genes in order to stratify a patient population to better determine who will respond most favorably (or at all) to a therapeutic.
“This is more an FDA regulatory term since some companies are now required to provide a companion diagnostic whenever they are approved for a therapeutic. The idea is to improve patient treatment by stratifying patients into responder or nonresponder populations,” noted Richard Montagna, Ph.D., senior vp, business development, Rheonix.
Dr. Montagna said the challenge for companies is to determine when to invest the time and effort to develop the companion diagnostic for the corresponding therapeutic.
“The problem with investing the effort up front is that the therapeutic or diagnostic could fail in clinical development and then the investment has been wasted. On the other hand, delaying the diagnostic development can jeopardize timely completion of the drug trials as the therapeutic and diagnostic submissions must be FDA-reviewed simultaneously. Moreover, approval for both is required to market the drug. Companies as well as the FDA are grappling with this issue.”
In the meantime, Rheonix has developed a fully automated platform for companion diagnostics called the Rheonix CARD® system that processes a range of clinical specimens.
“There are a number of platforms in the market, but none have the versatility that we have been able to achieve for this miniaturized system. For example, many systems evaluate only microliter volumes, but sometimes this is not suitable such as for septicemia. Our microfluidic-driven system uses inexpensive plastic, disposable devices with all the required functionality for multiplexing PCR of samples with volumes from 5 microliters to 5 milliliters.”
The system is also suitable for buccal swabs, whole blood, fresh tissue, and FFPE samples. Each can be placed into the system for automatic, unattended cell lysis, DNA extraction and purification, PCR-based amplification of targets, and detection of amplicons on an integrated DNA microarray.
The company will perform its first clinical study at four sites by year-end. “We have developed a Rheonix Warfarin assay for warfarin sensitivity. Patients are given warfarin to reduce the chance of stroke-causing blood clots.
“But warfarin is metabolized differently depending on patients’ genotypes. If the drug is metabolized too rapidly, they risk throwing a clot; too slowly, and they risk bleeding out in the brain. Currently assessments are made by repetitive blood tests that take weeks or months to get the right dose. Using our CARD system, a definitive test can be done within a few hours.”
Rheonix also has programs using the CARD technology to detect the presence of single nucleotide polymorphisms associated with Plavix sensitivity and KRAS markers, among others.
Clearly, the arena of molecular diagnostics is a field on the move. Modifying and integrating technologies such as PCR-based target enrichment, NGS, and mass spectrometry are leading candidates for new synergistic approaches.