KIRKLAND, Wash.—A key benefit of liquid biopsies, beyond being much less invasive than tissue biopsies, is a matter of easy access. Not all tumors are accessible for tissue biopsy, but even early in cancer development, cancerous cells are sloughed off into the bloodstream that can answer questions about cancer type and stage. In addition, liquid biopsies via blood draws are easily repeatable. Eventually, liquid biopsies could offer the ability to get a picture of a patient’s cancer much earlier in the disease state, which can drastically increase the odds of successful intervention.
Within this field, Resolution Bioscience Inc. recently announced that its Resolution HRD liquid biopsy assay had received Breakthrough Device Designation from the U.S. Food and Drug Administration. The assay is a qualitative in-vitro diagnostic for detecting sequence variations in key genes related to homologous recombination deficiency (HRD) for single nucleotide variants, indels and copy number variants.
Moving forward, Resolution intends to seek approval for the assay as a companion diagnostic—and if it gains that approval, it could be the first assay to detect gene deletions from cell-free DNA (cfDNA) and differentiate between single copy and biallelic (homozygous) gene deletions via a blood sample.
“This Breakthrough Device Designation from the FDA is an important step forward for the company,” said Mark Li, CEO of Resolution Bioscience. “For many patients, tissue biopsies are not possible or do not yield evaluable samples. We hope that our fast, accurate and non-invasive technologies may offer additional options for patients and also help our pharmaceutical partners accelerate their development efforts.”
Detecting cells and cfDNA of interest from liquid biopsies requires extremely specific, precise technology. As explained by Resolution Bioscience, “The circulating tumor DNA (ctDNA) may be less than 0.1 percent of all the cfDNA. Therefore, there may be tremendous amounts of background "noise" obfuscating each meaningful signal. The fragments are all made of the same material: DNA. Therefore, it is harder than a needle in a haystack—you are actually looking for one slightly different needle in a large pile of needles.
“The haploid human genome contains 3 billion bases. Some driving mutations are single nucleotide variations (SNVs), where a single base change has occurred. For example, an adenine (A) becomes a guanine (G). Some of the SNVs are heterozygous mutations, so instead of one in three billion, it's actually a mutation of one in six billion bases. If trying to reach a detection limit of 0.1 percent of ctDNA in 99.9 percent background cfDNA, the problem becomes the ability to detect one molecule in six trillion bases.”
Resolution's HRD assay, supported by its patented cfDNA NGS analysis platform, has been explored in a number of studies. With it, Resolution was the first company to demonstrate gene deletion detection in cfDNA in a small cell lung cancer study led by Vanderbilt University researchers, who found that cfDNA sequencing enables improved disease monitoring, treatment response monitoring and warning of relapse. In a publication by AstraZeneca, Resolution's technology showed the highest positive predictive value and lowest false-positive rate of four leading NGS liquid biopsy companies in a blinded comparison study.
On the topic of leading liquid biopsy contenders, Canaccord Genuity diagnostics analyst Mark Massaro wrote in a note to investors that Guardant Health (GH), Natera and Illumina are all companies to keep an eye on within this space. He expects growth for the space as a whole, as well, particularly in determining treatment options for patients with advanced cancer, as well as in recurrence monitoring and minimal residual disease detection. Massaro also noted that Canaccord Genuity expects to see liquid biopsy testing begin to replace tumor profiling.
A recent MEDACorp specialist call hosted by SVB Leerink LLC looked at liquid biopsy within the gastrointestinal field, and also touched on Guardant Health as a player to keep an eye on, calling the company a “best-in-class liquid biopsy opportunity in a massive high-growth market.” Leerink noted that call participants felt that “Recurrence or residual disease monitoring opportunity remains most promising for [GH] and its LUNAR assay—with potential to reduce adjuvant trial size significantly and improve patient selection—making it, in our view, highly attractive for biopharma and for commercial post-surgical/treatment testing.” However, both participants agreed that Guardant Health data for LUNAR seemed to be five or more years away from the colorectal cancer screening market.
The participating oncologist said that “GH's recent data on the LUNAR LBx assay holds the most promise in recurrence monitoring and adjuvant therapy trials. The Oncologist expects that LUNAR can help reduce trial size, cost and turnaround time for adjuvant therapy by 80 percent in certain cases—only selecting those patients that are most likely to relapse—an attractive proposition for biopharma.”
The recurrence market especially has significant potential, with Guardant estimating that the overall recurrence monitoring market for all cancers is $15 billion.