If companion diagnostics (CDx) were people, they would be old enough to drink. The first CDx won FDA approval in 1998, when Dako Denmark (since acquired by Agilent Technologies) received authorization to market HercepTest. The immunohistochemistry (IHC) assay was designed to detect human epidermal growth factor receptor 2 (HER2) protein overexpression in breast tumors of patients who may benefit from Herceptin (trastuzumab), a targeted therapeutic for certain types of breast cancer marketed by Genentech (now a member of the Roche Group).
As of June 19, the FDA listed 38 cleared or approved CDx “devices” on its website. The CDx market is projected to more than triple from $3.153 billion in 2018 to $10.656 billion in 2025, according to Energias Market Research, which forecasts a compound annual growth rate of 19% between 2019–2025.
Following are profiles of eight CDx developers to watch for their track record, including recent activity in the field.
Agilent Technologies added to its 20-year history of success in companion diagnostics, starting with HercepTest launched in 1998, when the company received FDA approval on June 10 for expanded use of its PD-L1 IHC 22C3 pharmDx assay to identify patients with head and neck squamous cell carcinoma (HNSCC) for treatment with Merck & Co. programmed death 1 (PD-1) immunotherapy, Keytruda (pembrolizumab). Two months earlier, on April 16, the FDA approved the assay to identify a broader range of patients with stage III or metastatic non-small cell lung cancer (NSCLC) for first-line treatment with Keytruda.
Agilent’s PD-L1 IHC 22C3 pharmDx along with PD-L1 IHC 28-8 pharmDx, indicated for use with Bristol Meyer Squibb’s immunotherapy, Opdivo (nivolumab), are approved for multiple tumor indications and hold 85+ global product registrations, according to Nina Green, vice president and GM of the Companion Diagnostics Division at Agilent Technologies. These assays are used to identify patients more likely to respond to immunotherapies, or to determine PD-L1 status to inform physicians considering treatment options for cancer patients.
“Understanding what it takes to bring a companion diagnostic assay successfully to market, Agilent is innovative, collaborative, and nimble, which ensures we constantly stay aligned with our pharma partners and their evolving requirements through the entire process: development, regulatory, manufacturing, and commercialization,” Green said. “Agilent’s solid reputation for high-quality, world-class products and service make us uniquely suited to partner with pharma for companion diagnostics.”
A full-service provider to pathology labs worldwide, Agilent’s portfolio consists of instrumentation, reagents, and software. Agilent’s large commercial channel and instrument footprint enable the company to secure access to key labs and clinicians. “Agilent also has solutions and expertise across multiple modalities spanning genomics, proteomics, and metabolomics, which provides significant capacity for growth and support of future companion diagnostics partnerships,” added Simon Oestergaard, GM and vice president of Agilent’s Pathology Division.
Best known for its top-tier next-generation sequencing (NGS) instruments, Illumina won additional market attention for its companion diagnostics in January, when it received the FDA’s Breakthrough Device designation for its developmental-phase pan-cancer assay, to be marketed as TruSight Oncology Comprehensive.
The assay is based on Illumina’s TruSight Oncology 500 (TSO 500) test, an NGS tumor profiling assay designed for detection and analysis of known and emerging solid tumor biomarkers. Launched in October 2018, TruSight Oncology 500 uses both DNA and RNA from subject tumor samples to identify key somatic variants underlying tumor progression, such as small DNA variants, fusions, and splice variants. TruSight Oncology 500 can measure tumor mutational burden (TMB) and microsatellite instability (MSI), targeting 523 genes for SNV and indel detection and 55 genes for fusion and splice variant detection.
“As we move to bring a future in vitro diagnostic version through regulatory approval, we will be able to set the standard for accurate and reproducible testing,” said Garret Hampton, executive vice president of Clinical Genomics at Illumina. “Today’s value in the capability to call for TMB is in line with current research and emerging guidelines, but the promise that TruSight Oncology 500 holds for the future identification of biomarkers makes it a robust solution for this rapidly evolving field.”
Illumina says it is committed to bringing the power of NGS to clinical diagnostics, delivering CDx solutions to its pharmaceutical partners and clinical testing labs by building on the status of the Illumina MiSeqDx System as the first FDA-regulated and CE-IVD-marked NGS instrument for use in in vitro diagnostic procedures.
“By focusing on our most differentiated oncology products, we can meet the needs of our customers and provide a comprehensive NGS panel that includes all of the known and anticipated biomarkers associated with targeted and immune-based therapies,” Hampton added.
QIAGEN has been among the busiest companion diagnostics developers this year. On May 24, QIAGEN launched its therascreen PIK3CA RGQ PCR Kit following FDA approval as a CDx for identifying breast cancer patients eligible for treatment with Novartis’ Piqray (alpelisib). Eight days earlier, QIAGEN and Inovio Pharmaceuticals agreed to co-develop a CDx for Inovio’s DNA-based immunotherapy candidate VGX-3100 to treat cervical dysplasia caused by human papillomavirus (HPV). And in April, QIAGEN launched therascreen FGFR RGQ RT-PCR Kit as a CDx with Janssen Biotech’s approved FGFR kinase inhibitor Balversa (erdafitinib).
Following more than a decade of partnering with biopharmas, QIAGEN has developed companion diagnostic assays for seven FDA-approved therapies. The company says it is collaborating with more than 25 companies to develop and commercialize CDx assays.
“Such a deep pipeline of experience and expertise allows QIAGEN to act as true consultants ensuring the best solutions for our partners,” Reinhard Ortmann, Ph.D., QIAGEN’s director of companion diagnostic development, told Clinical OMICs. “We uniquely offer both real-time PCR and NGS-based companion diagnostic development within a complete Sample to Insight workflow. We are able to align drug and diagnostic development to achieve simultaneous approval, and we can even provide pharma global clinical trial sample testing.”
QIAGEN serves and supports more than 500,000 labs in more than 35 countries, with distributors in 70 countries. Ortmann said QIAGEN is well-positioned to develop a global lab network strategy and prepare reference labs for CDx readiness at time of drug launch.
“At QIAGEN, we accelerate the development, validation, and commercialization of companion diagnostics so that labs can implement patient testing the same day the drug gains approval,” Ortmann said.
QIAGEN’s Day-One Lab Readiness program builds on the FDA’s updated regulatory approach designed to help identify patients who might benefit from a new treatment option earlier, saving valuable time and money, Ortmann added.
Thermo Fisher Scientific
Thermo Fisher Scientific’s Oncomine Dx Target Test anchors the company’s companion diagnostic effort, part of a specialty diagnostics business segment whose revenue rose 7% last year, to $3.72 billion.
In 2017, the company became the first to win FDA approval for a multi-marker, NGS-based CDx oncology test when Oncomine Dx was authorized for simultaneously screening tumor samples for biomarkers associated with three FDA-approved therapies for non-small cell lung cancer (NSCLC)—AstraZeneca’s Iressa (gefitinib), Pfizer’s Xalkori (crizotinib), and Novartis’ combination of Tafinlar (dabrafenib) and Mekinist (trametinib).
Oncomine Dx Target Test is able to simultaneously evaluate 46 cancer-driver gene variants using as little as 10 nanograms of DNA and RNA. Oncomine Dx Target Test has been CE-IVD marked in Europe and also received regulatory approval in South Korea and Japan. On February 27, Japan’s Ministry of Health, Labour, and Welfare granted expanded approval to include three additional NSCLC biomarkers that have a total of eight associated targeted therapies.
“This milestone has led to several signed CDx development agreements with major pharmaceutical companies that want to leverage our Oncomine Dx Target Test as a CDx for certain targeted therapies in their pipeline. We also have multiple partners in China that enable both clinical trials and CFDA-approved assays to be developed for that market,” said Andy Felton, vice president of product management, clinical next-generation sequencing and oncology at Thermo Fisher Scientific.
Felton said experience with global regulatory bodies is one key factor Thermo Fisher cites for its success in CDx; the other is the company’s global presence.
“Our comprehensive regulatory, development, reimbursement, go-to-market expertise, and global commercial footprint allows for a fast and reliable path for any drug developer to gain a CDx approval and commercialize with maximum impact,” Felton added.
Foundation Medicine achieved its first key companion diagnostics approval in November 2017 when its FoundationOne CDx won the FDA’s first market authorization for a comprehensive genomic profiling assay for all solid tumors incorporating multiple tests. The following June, majority owner Roche spent $2.4 billion to expand its stake into full ownership of the cancer-focused molecular diagnostics developer, in a deal that signaled the pharma giant’s growing interest in personalized oncology treatments as well as diagnostics.
Foundation Medicine—now a separate and autonomous company within the Roche Group—says its portfolio of comprehensive genomic profiling (CGP) tests, robust genomic data and insights, and strong network of physicians uniquely positions the company well for partnering with drug developers.
In May, Foundation Medicine and Bayer launched a global collaboration to develop and commercialize NGS-based companion diagnostics across multiple oncology drug candidates and approved therapies developed by Bayer. The deal covers FoundationOne CDx and the rest of Foundation Medicine’s test portfolio, which includes the FoundationOne Heme test for hematologic malignancies and sarcomas, and FoundationOne Liquid, a liquid biopsy test for solid tumors launched last year as a next-gen version of FoundationACT.
Foundation Medicine’s commitment to providing physicians and partners with a rigorously-validated portfolio of CGP tests is a key factor in the company’s success, CEO Cindy Perettie told Clinical OMICs.
“We’re proud to collaborate with more than 50 biopharmaceutical companies to help drive precision medicine forward in pursuit of better outcomes for patients,” Perettie said. “Our partners depend on the rigor and comprehensiveness of our genomic tests, robust real-world data and our commitment to continued innovation to achieve more efficient therapy development.
From its inception in 2006, the mission of MolecularMD, an ICON plc company, has been to empower therapeutic/diagnostic co-development with strategies that mitigate risk and that nimbly adapt to accelerated approval timelines.
MolecularMD—acquired by ICON earlier this year—cites capabilities that include combining technical expertise with proven end-to-end capabilities in development and approval of therapeutics and diagnostics for oncology precision medicine. The company can develop and manufacture a test both independently with drug sponsor and through three-way partnerships with drug sponsors and IVD/platform partners.
“MolecularMD’s distinction is premised on the fact that diagnostic strategies and challenges for each therapeutic program are unique and often change course with limited notice,” MolecularMD President Dan Snyder told Clinical OMICs. “The ideal diagnostic partner needs to excel in technical, clinical, quality, regulatory, and commercial diagnostic competencies while collaboratively planning and navigating the translational, clinical, and commercial phases of the therapeutic program.”
The company’s MRDx BCR-ABL Test was authorized by the FDA in 2017 as a CDx for treatment-free remission in Philadelphia chromosome positive (Ph+) chronic myeloid leukemia patients in the chronic phase being treated with Novartis’ Tasigna (nilotinib). Last year, MolecularMD signed a non-exclusive collaboration agreement with Sysmex toward CDx development and commercialization.
Factors in MolecularMD’s success, Snyder said, include its experience in drug-diagnostic co-development, and its scientific and development expertise.
“Our organizational structure and supporting processes allow for rapid development and deployment of ‘fit for purpose’ tests, ranging from RUO, CTA, IUO, and IVD for both tissue and plasma-based assays. MolecularMD also acts as a central laboratory testing partner so we can develop and deploy a test in rapid succession,” Snyder said. “For post approval, MolecularMD retains an experienced team dedicated to planning and execution of IVD commercialization, including programs to support U.S. reimbursement and global distribution. And now, with MolecularMD being part of ICON, we have greater breadth and depth in what we are able to offer our clients.”
Myriad Genetics cites its pioneering role in molecular diagnostics, with more than 20 years of experience discovering, developing, and delivering transformative molecular diagnostics to patients.
The company’s BRACAnalysis guides treatment decisions by analyzing the BRCA1 and BRCA2 genes to assess a woman’s risk for developing breast and ovarian cancer. Other Myriad CDx offerings include Cell Cycle Proliferation Assay, a proprietary element of Myriad’s Prolaris test, which, with other clinical parameters, assesses prostate cancer aggressiveness; and PREZEON, which assesses loss of PTEN function in cancer patients.
“Myriad offers several advantages to help our pharmaceutical company partners succeed, including biomarker discovery, clinical research, regulatory and commercialization support,” said Patrick Burke, Ph.D., executive vice president, emerging products, Myriad Genetics. “Myriad offers a menu of ‘off-the-shelf’ molecular diagnostic products that are commercially available to our pharmaceutical partners.”
In February, Myriad announced that its BRACAnalysis CDx successfully identified patients with metastatic pancreatic cancer who have BRCA mutations and benefitted from treatment with AstraZeneca’s Lynparza (olaparib) in the Phase III POLO trial (NCT02184195). Two months later, Myriad submitted to the FDA the first module of its PMA for its myChoice HRD CDx test, intended to identify patients with ovarian, fallopian, or primary peritoneal cancer who may benefit from Zejula (niraparib), marketed by Tesaro, a GSK (GlaxoSmithKline) company.
Also in April, Myriad expanded its CDx collaboration with AstraZeneca and Merck & Co. The companies agreed to use BRACAnalysis CDx to identify germline BRCA mutations in men with metastatic castrate-resistant prostate cancer (mCRPC) who are enrolled in the Phase III PROfound trial (NCT02987543).
“In situations where a pharmaceutical company needs a custom assay of its own design, Myriad offers a simple and flexible fee-for-service protein biomarker assay platform to create partner-driven assays and test research hypotheses,” Burke said. “Once a pharmaceutical partner’s clinical trials are completed, the Myriad regulatory team works to ensure FDA approval of companion diagnostics, while the company’s commercial team helps support physician education, test adoption and our pharmaceutical partners’ successful commercial launch.”
While Foundation Medicine has grown Roche’s presence in companion diagnostics, the pharma giant’s CDx activity is also being expanded through its Roche Diagnostics division. Roche Diagnostics finished 2018 with a 6.6% sales increase to CHF 12.879 billion ($12.892 billion), driven partially by a 9% jump in companion diagnostics, part of its Tissue Diagnostics business area.
Roche doesn’t further detail CDx results, but has said more about recent activity. Last year, Roche’s cobas EGFR Mutation Test v2 won FDA approval as a companion diagnostic with AstraZeneca’s Iressa (gefitinib) for first-line treatment of patients with non-small cell lung cancer (NSCLC).
On April 23, Roche launched its VENTANA HER2 Dual ISH DNA Probe Cocktail same-day assay, designed to detect the HER2 biomarker in breast and gastric cancer patients who may be eligible for Herceptin (trastuzumab), marketed by Roche and its Genentech subsidiary.
“As the market leader in diagnostics, we offer the largest number of placements across geographies, ensuring that patients have access to pivotal drugs as quickly as possible,” Christoph Majewski, vice president, companion diagnostics, Roche Tissue Diagnostics, told Clinical OMICs. “Our medical teams work closely with pharma partners to provide clinicians with education and training on new assays to ensure rapid access to groundbreaking treatments.
Majewski noted that Roche Tissue Diagnostics was among the first companies to recognize this with the launch of the HER2 antibody to triage breast cancer patients for treatment with Herceptin.
“In the 15 years since, Roche has gained deep experience in the development and launch of companion diagnostic assays. Roche Diagnostics has established an exemplary track record in supporting pharmaceutical companies in bringing new therapies to patients—collaborating with more than 70 partners on over 200 companion diagnostics,” Majewski added.