Qiagen's plans for the software intellectual property it acquired along with CLC Bio and Ingenuity Systems include bundling the CLC Genomics Workbench with its Gene Reader sequencing instrument and launching a new variant analysis product next year to support next-generation sequence-based clinical testing and reporting.
Last week, at the Association for Molecular Pathology meeting in Phoenix, Ariz., Qiagen announced that it has begun enrolling commercial and academic clinical labs in an early access program to test the yet-to-be-named web solution.
Input from these participants, including Partners Healthcare, Emory Genetics Laboratory, and GeneDx, is helping to drive the development of the software which "will simplify and streamline the interpretation and reporting process and provide consistent, high-quality, and actionable results for use in clinical research and decision making,” Sean Scott, senior vice president of business development at Qiagen Redwood City — formerly Ingenuity — said in a statement last week.
This week, Scott and Thomas Knudsen, vice president and head of bioinformatics of Qiagen, Aarhus, and former CEO of CLC Bio, provided some details about the software to analysts at meeting in New York. Essentially, it's a platform for interpreting and reporting the results for sequencing-based molecular diagnostic tests that will automatically score and classify variants based on "comprehensive evidence" from literature and other sources so that labs "can more quickly and confidently make clinical assessments [based] on those variants," Scott explained to BioInform at the meeting.
The system classifies variants based on primary information collected from scientific literature, supplemented with data from pharmacogenomic resources; guidelines from Food and Drug Administration labels, the National Comprehensive Cancer Network, and the American Society of Clinical Oncology; clinical trials data; and third party locus-specific databases, among other sources.
Labs can "set up the rules by which they want to score and classify variants for each test indication, as well as set up their desired reporting rules and methods so that … the system only provides the specific number of variants that they have chosen to do a manual review of based on their reporting rules," Scott said. Also, users can add to the system new information about variants they observe in patients, if they have it, and that data is incorporated into the system's knowledgebase and applied to the results of future tests. Finally, there is an automated reporting engine for returning the final variant list to requesting clinicians.
Qiagen Redwood City has been developing its clinical product for sometime now working with partners such as the Laboratory Corporation of America, Life Technologies, and GeneInsight, a wholly owned subsidiary of Partners HealthCare. As part of its efforts to develop this and other clinical interpretation and reporting solutions, Qiagen has formed a scientific advisory board that includes representatives from Partners, GeneDx, University of Pennsylvania, the Genome Institute at Washington University School of Medicine, and others, many of whom are participating in its EAP.
The EAP's objective, according to Scott, is to check that the product adequately addresses an "unmet need" for more automated clinical assessment tools and to validate the product's approach to scoring and classifying variants. The company intends to support tests that target hereditary conditions and cancer and is working with its partners to curate variants associated with hereditary cancer and other inherited diseases, somatic cancer, carrier screening, and cardiomyopathy.
In January, following the EAP, Qiagen will launch a larger beta program to further test the software before its launch in Q1 next year. It has set up a form on the Ingenuity website and is accepting applications from interested labs that currently either offer or plan to offer NGS-based genetic tests that are in line with the test indications that the software will support.
"We will probably add a few more labs [to the EAP] before the end of the year," Scott said. Then "assuming that we keep our objectives in the early access program, we will shift to a more formal beta testing program for select test indications in the January/February time frame with the goal to make the application commercially available in the March  time frame."
The new clinical offering, he said, shares some commonalities with research-centric Ingenuity's Variant Analysis software. For example, both tools make use of Ingenuity's knowledgebase of biological and chemical information, and they'll both accept VCF files from CLC Bio's software as input. Where the products differ is on the sorts of data they use for analysis with the clinical software incorporating more information than its research counterpart does. In addition to variant calls, it incorporates metadata about the test being run, as well as patient and clinical information such as sex, age, and ethnicity.
When it goes to market next year, the new solution will be marketed to CLIA labs that are developing sequence-based screening, diagnostic, or prognostic tests. That list includes labs that have just now begun considering NGS-based testing and want access to a comprehensive source of information to interpret the variants that their tests might look for, as well as labs that have already successfully launched sequencing-based tests that cover a small number of genes and variants but who are looking to scale up.
"From a coverage perspective, our goal [for the solution] is to manually curate substantially all of the gene-disease to phenotype content from scientific literature so that … that we have comprehensive coverage from the primary evidence perspective on those genes" and to complement it with information from other sources such as clinical trials so that these labs can launch their tests, Scott said. In addition, the solution will automate the process of scoring, classifying the observed variants and generating reports, he said.
"We view the ability to interpret [and] report on sequence-based testing as really the rate-limiting factor for NGS in clinical environments today," Scott said. Currently, "a typical lab director might spend anything from 20 minutes to three hours researching an observed variant and if you think about … sequencing-based tests in terms of the types of variants [and] the types of phenotypes they are encountering, as well as the types of tests they are running," without automation, "the complexity is unmanageable."
Meanwhile, in terms of integrating its software into Qiagen's product portfolio, CLC Bio is pursuing two lines of development. The first, which Qiagen made clear when it announced that it had bought the company last month, involves combining CLC Bio's and Ingenuity's products into a single informatics workflow tailored for its yet-to-be-launched GeneReader benchtop sequencer, thus providing customers with tools to analyze data coming off the sequencer through to variant interpretation. CLC Bio's Knudsen told BioInform this week that when the sequencer starts shipping, orders for Gene Reader will include a specialized version of the CLC Genomics Workbench software that has a pipeline for analyzing specific Qiagen gene panels.
"It's going to be optimized to analyze the panels that Qiagen will sell but [it could] also be used for … other things," he explained. Basically, "users will be able to switch back and forth between [the] research workbench and … another view where you will work with the gene panels that Qiagen is developing."
Knudsen added that customers will likely get a first look at the gene panel analysis pipeline during an early access program for Gene Reader and that the company will roll out that product when Qiagen's sequencer launches — the company has not disclosed precisely when that will happen.
Meanwhile, CLC Bio will continue to sell standalone versions of its software to its customers who want to use instruments other than Gene Reader in market segments such as pharmaceuticals, biomedicine, and agriculture. This is in keeping with Qiagen's strategy providing customers with the tools they want and allowing them to purchase only the components that they need, Knudsen said.
This same development principle holds true for Ingenuity and its products. And that’s good news for both companies' customer bases, many of whom use non-Qiagen products, according to both Scott and Knudsen. For instance, large swathes of their clients currently use Illumina's instruments for sequencing — about 90 percent of existing research customers in Ingenuity's case, Scott said.
"There'll be a very tight integration with the primary and secondary analysis and initial annotation service that CLC provides," he told BioInform, but because most customers prefer not to be dependent on a single provider "we will continue to work with other platform and service vendors as well."
Ingenuity already has partnerships with sequencing vendors like Life Technologies, which combined Ingenuity variant analysis with its Ion Reporter analysis software for its Ion Personal Genome Machine and Ion Proton Systems; and Complete Genomics, which last year merged with BGI around the same time it signed a pact with Ingenuity to offer customers of its research whole-genome sequencing service access to the company's variant analysis capabilities.
Scott and Knudsen also said that they'll continue to pursue the internal development roadmaps that they had prior to being acquired by Qiagen. Both firms are investing primarily in developing products to support Qiagen's sequencer and assay portfolio, but "we still have business plans," Knudsen said.
And being part of Qiagen will help bring those plans to fruition. "We both had ambitious missions where they may not have been achievable on a standalone basis but as we bring these organizations together … it does open up a larger market opportunity for us," Scott said.
Commenting specifically about Ingenuity's clinical product, he added that "having [access to] the level of expertise the Qiagen has in terms of regulatory reimbursement [and] understanding the unique unmet needs and requirements at [the] molecular diagnostic or pathology lab level is tremendously valuable to us in advancing that new business and new product offering and that is not something we could have done independent of Qiagen."
Furthermore, their respective standalone products will benefit from increased resource investment, as well as access to a larger sales and marketing force, Knudsen added. There are also opportunities to bundle both CLC Bio's and Ingenuity's software with more products in Qiagen's portfolio enabling the company to "maximize the value" it provides to customers, he said.
Besides creating more comprehensive product offerings for the market, there's also room to foster existing partnerships with vendors in the space that offer similar products to those in Qiagen's sequencing and informatics pipeline, Scott said. "We'll continue to work strategically with Life [Tech] and what they are doing from an Ion Reporter workflow perspective; we'll continue to focus on supporting Illumina's customer base and helping them analyze and interpret their data; [and] we'll continue to work with service providers such as BGI and others."
But the company is also open to forging new partnerships with companies who, for example, couple sequencing and informatics. Scott pointed out that Ingenuity has invested millions over the past 15 years in building out the knowledgebase that underlies Ingenuity Variant Analysis and other software that it's developed. "If you simplify it down to [only] content, with content being the foundation for understanding genomes and disease, it really doesn’t make any sense for [these] organizations to try to replicate what we've done," he said. "It may not be a long-term sustainable advantage whereas for us it can be."
In terms of product prices, CLC Bio will continue to operate the same licensing structure that it has had in the past as this has proven to be a successful strategy for the research market, Knudsen said. The company currently offers single-user, department, and site licenses — it does not disclose how much each license costs.
Meanwhile, Qiagen is still mulling pricing and marketing options for Ingenuity's clinical product, Scott said. He said that the firm has identified three pricing models that labs seem to prefer. The first would involve charging a fixed fee per reportable test; the second would involve charging a royalty fee based on test revenues or reimbursement levels, and the third would be to charge a fixed cost for enterprise-level access, which might be appropriate for high-throughput labs that handle a large number of tests annually.
Ultimately, "the market will largely dictate the business model," he said. "Our goal is … pricing that’s aligned with perceived value and scalable whether it be research or clinical."