NEW YORK (GenomeWeb) – Bio-Rad Laboratories is moving its Droplet Digital PCR platform and liquid biopsy assays further into the commercial clinical space with recent regulatory approvals and submissions.
Bio-Rad recently provided glimpses into its IVD strategies for the platform in a number of forums, illustrating the challenges and opportunities it sees going forward as it potentially introduces the technology to new users and expands its customer base.
The company received CE-IVD marking on a Droplet Digital PCR kit to detect BCR-ABL gene fusions last month. The test, which is Bio-Rad's first clinical ddPCR assay to receive regulatory approval of any kind, is blood-based and designed to monitor treatment response in patients with chronic myeloid leukemia.
At the JP Morgan Healthcare conference this week, Bio-Rad's CEO Norman Schwartz affirmed that obtaining regulatory clearances for liquid biopsy IVD tests is a high priority for the firm. "We expect this to be a substantial area of growth for us," he said.
However, Schwartz also noted that a challenge to adoption of liquid biopsy in general rests in the fact that it takes time for people to get used to using new technology.
Mitigating this might be the roughly 2,400 peer-reviewed studies incorporating ddPCR to date. In fact, the technology has been used extensively for research purposes since Bio-Rad acquired it in 2011.
In the firm's recent annual investor day presentation, Annette Tumolo, executive vice president of Bio-Rad and president of the life science group, said about half of its current ddPCR customers use the technology for basic research, while 30 percent use if for biopharma applications, and 20 percent use if for liquid biopsy or diagnostic purposes.
Asia-Pacific is the most rapidly growing region for the platform, Tumolo said. It currently represents 30 percent of ddPCR revenue but this is increasing due to "really aggressive adoption of this technology for liquid biopsy in China." About 70 percent of ddPCR-related revenues come from instrument sales, but Tumolo said the firm is on track to achieving an even split between platform sales and consumable sales in 2018.
Tumolo said that the move of this technology from translational labs into lab-developed clinical tests was "astonishingly fast." The next step is to take digital PCR into the regulated IVD markets with CE-IVD and US Food and Drug Administration-cleared products, she also said.
Market research consensus suggests there will be around a $2 billion market for liquid biopsy by 2021, with a double-digit growth rates over the next few years, according to her investor day presentation. However, Droplet Digital PCR has already been adopted by Bio-Rad's customers into this market, Tumolo asserted.
Bio-Rad sees the liquid biopsy market as divided into four segments: early detection and screening, diagnosis, therapy guidance, and residual disease monitoring, Tumolo said. The company believes its fastest route to getting ddPCR on the market with a menu of tests is to initially focus on the residual disease monitoring and therapy guidance segments, which comprise an estimated 40 percent of the market currently, she said.
The firm is now in the process of preparing its BCR-ABL blood cancer test for FDA submission, she said, but it is also cognizant of many diagnostics opportunities outside of liquid biopsy that could be pursued in the future.
Enabling customers to continue to put lab-developed tests onto the platform, in addition to the menu developed by Bio-Rad, will also be important for broad adoption, Tumolo asserted.
Finally, the company is also considering partnering with third-party kit developers to put content on its platform. "We think this strategy will provide us the broadest dive into the liquid biopsy market," she said.
In an interview, Lisa Jensen-Long, Bio-Rad's VP of marketing at the Digital Biology Group, said that clinical diagnostic customers are not new to Bio-Rad, as they have been using many of the company's clinical products for decades.
"For new customers, we have a commercial plan for education and outreach that we will roll out as we begin to execute our IVD strategy," Jensen-Long said, adding that in North America the firm has "a specialty genomics team comprised of sales, marketing, field application scientists, and scientific affairs experts" who will train and support its customers.
The firm chose the BCR-ABL test as its first foray into regulated IVD because although there are many other laboratory-developed tests for monitoring BCR-ABL on the market, these demonstrate a variety of performances and significant differences from lab to lab, Jensen-Long said.
"Bio-Rad could have chosen a much easier first test to submit for FDA approval as many other molecular diagnostic companies have done; however, having a test that is approved by the FDA and distributed to all molecular diagnostic laboratories will allow standardization of testing with a highly sensitive and accurate method," she said.
A study using Bio-Rad's ddPCR showed a lower limit of detection and quantification than standard qPCR methods for BCR-ABL monitoring, while research published last year using another dPCR method from Fluidigm suggested the technology in general can better detect residual disease than other PCR-based approaches.
Bio-Rad is currently in the middle of clinical trials for BCR-ABL monitoring for CML and intends to submit data to FDA early in 2018, Jensen-Long said.
In alignment with recent FDA practice, immediately following BCR-ABL, the company will submit its QXDx open IVD platform in order to support clinical laboratories with compliant LDT assays, she added.
Overall, the company has "built the ddPCR space from the ground up," Jensen-Long said, and it does not see significant competition within the space at this time. The technology also continues to have advantages in precision and accuracy over qPCR competitors, she said, and Bio-Rad expects to take market share away from that segment.
"We could see some downward competitive pressure from NGS if that technology can become faster, simpler, and inexpensive enough to use in low multiplex applications," Jensen-Long said. In the meantime, Bio-Rad is continuing to expand its ability to query a larger number of markers and variants per reaction to maximize sensitivity when limited DNA is available, such as in liquid biopsy samples, and it will also continue to further streamline the ddPCR workflow.
In terms of competition from other technologies being used for CML monitoring, a BCR-ABL test kit from Asuragen received premarket clearance from the FDA last year, becoming the first such kit commercially available in the US, and the firm has since launched a CE-marked kit to detect minor fusions. A BCR-ABL test from Cepheid was CE marked in late 2015.
Jensen-Long noted that ddPCR as an enabling technology has "strong value across the clinical spectrum, from primary diagnosis and companion diagnostics, to monitoring." Further evolution of the ddPCR ecosystem will include "higher-plex panels, a fully integrated and hands-free system, and development of a sample-to-answer platform," she said.