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Two consortia set up in recent weeks aim to create centralized cancer diagnostics that can be used to guide therapeutic decision making. On August 21, San Diego-based Illumina teamed with AstraZeneca, Janssen and Sanofi to work on an oncology test that can simultaneously analyze multiple genes and variants from a single tissue sample. Underpinning the effort, Illumina said on September 8 it had created the Actionable Genome Consortium with the Dana Farber Cancer Institute, the Fred Hutchison Cancer Research Center, the MD Anderson Cancer Center and the Memorial Sloan Kettering Cancer Center to support the use of NGS in clinical oncology practice. On September 25, Carlsbad, California–based Thermo Fisher Scientific announced a similar plan, working with GlaxoSmithKline and Pfizer, to develop its own universal companion diagnostic, based on markers from its Oncomine Cancer Research panel. “With NGS there’s an unprecedented ability to do multi-analyte analysis, and the cancer community has begun applying it to analyze tumors,” says Naomi O’Grady, senior manager, product marketing for oncology at Illumina. “Moving [a universal test] forward as a companion diagnostic emerged quite naturally,” and will make it easier for pharmaceutical companies to bring targeted therapies to market, she says. The advantage of a univer-
Dow’s newly approved Enlist fights superweeds The Environmental Protection Agency gave Dow AgroSciences final approval on October 15 to commercialize its Enlist Duo herbicide. The new system will be sold in combination with corn and soybean plants genetically engineered for plant-optimized aryloxyalkanoate dioxygenase gene from plant soil bacterium Sphingobium herbicidovorans to tolerate Enlist, which were approved on September 17, 2014. Dow AgroSciences, a unit of Dow Chemical, said the biotech crops could be available for the 2015 planting season. The Indianapolis-based firm developed the herbicide in response to weedresistance problems resulting from the heavy use of the Roundup Ready system developed by Monsanto. The new herbicide is a blend of 2,4-d choline with glyphosate, the main ingredient in Roundup. Dow expects Enlist to be an effective tool to manage glyphosate-resistant weeds.
sal companion diagnostic is straightforward. As opposed to the one-biomarker, one-test approach—the way companion diagnostics have been developed thus far—a universal test allows researchers or clinicians to look at many different genes and mutations in a single sample. This reduces the amount of often painful- or difficult-to-obtain biopsy tissue needed, and provides much more actionable information to oncologists more quickly. “It’s become obvious that a one-test, multiple-drugs solution is required and that next-generation sequencing is best suited to carry out that one test,” says Dan Rhodes, head of oncology for life sciences solutions at Thermo Fisher Scientific. Take, for example, the specific indication of non-small cell lung cancer (NSCLC), for which two approved companion tests for epidermal growth factor receptor and anaplastic lymphoma kinase mutations may soon be joined by tests for BRAF oncogene and proto-oncogene tyrosine protein kinase ROS1 mutants. There is a host of drugs, in development or approved, that target those molecular subtypes. “If you only have a small tumor sample, as is often the case in NSCLC,” says Anne-Marie Martin, head of precision medicine and diagnostics and molecular medicine for the oncology therapy area at London-based GlaxoSmithKline, it creates a challenging situation for patients and physi-
J&J buys antiviral firm Alios Johnson & Johnson of New Brunswick, New Jersey, has snapped up Bay Area-based Alios BioPharma for $1.75 billion in cash. Founded in 2008 by three executives from InterMune, Alios had previously raised $73 million primarily from corporate venture capital arms Novo Ventures, SR One, Roche Venture Fund and Novartis Ventures. The company’s pipeline includes AL-8176 to treat respiratory syncytial virus and the nucleotide NS5B polymerase inhibitor VX-135 for the treatment of hepatitis C virus infections, both in phase 2 trials, as well as several preclinical compounds.
“The lack of a viable model for Alzheimer’s has been the Achilles’ heel of the field.” P. Murali Doraiswamy, an Alzheimer’s researcher at Duke University, commenting on the recent report of a culture model for Alzheimer’s disease that recapitulates the human disease. (The New York Times, 12 October 2014)
© K.C. Alfred/U-T San Diego/ZUMA Wire
npg
© 2014 Nature America, Inc. All rights reserved.
Illumina, Thermo Fisher build consortia to develop ‘universal’ cancer tests
Illumina’s CEO Jay Flatley is driving the sequencer supplier’s business strategy in the clinical space.
nature biotechnology volume 32 NUMBER 11 NOVEMBER 2014
“Thankfully, venture funders are starting to invest again in real, hard-core science and innovation.” John Sorenson, CEO of agbiotech Vesteron of Kalamazoo Michigan, which is developing pesticides based on natural venoms. The company just completed its third round of venture-backed funding, during a quarter where venture capital investment in biotech is set to exceed the peak year of 2008. (The New York Times, 12 October 2014) “It’s time for the people who run the biomedical research enterprise in this country to make basic research the center of their pitch for funding. Collins had a huge opportunity to do that here, but he blew it.” Michael Eisen, objecting to Francis Collins’ scare tactics to extort more funding for Ebola research rather than for basic research, whence things like vaccines derive. (It is NOT junk, 13 October 2014)
1073
npg
© 2014 Nature America, Inc. All rights reserved.
NEWS cians as there may not be sufficient tissue to run all available tests. Given industry’s focus on targeted oncology therapies across multiple indications, “the problem will become staggering across many cancer types over the coming years,” says Rhodes. “The Illumina collaboration simplifies our process of developing companion diagnostics,” says Nic Dracopoli, head of the biomarkers group at Janssen Oncology, in Spring House, Pennsylvania. “We’ve identified genes we’re interested in, and Illumina has agreed to do the analytical development of those genes to the point we can use them in prospective clinical studies.” Illumina plans to offer its pharma partners the use of the test to support clinical validation and US Food and Drug Administration (FDA) approval in combination with their drugs at some point in 2015. Still, regulatory, intellectual property (IP) and reimbursement wrinkles remain to be ironed out before these tests are part of everyday cancer care. The kind of comprehensive approach enabled by an NGS–based universal diagnostic means every available marker can be analyzed in a standardized manner. Those markers may be clinically validated—where patients selected for a given biomarker have benefited from a particular treatment—or based only on analytical claims that feed into companies’ research or clinical development strategies (Box 1). Thermo Fisher says its diagnostic will enable simultaneous testing of single-nucleotide variants, copy number variants, gene fusions and indels across 143 unique cancer genes. Among the genes in the new panel, 26 are targeted by oncology drugs currently on the market, and an additional 44 are used in determining eligibility for current clinical trials. The test is expected to look at about 3,000 total alterations. “The beauty of this panel is that some of the work we would have done retrospective to a study we can now do prospectively. Beyond patient selection, this approach allows us to generate more comprehensive molecular information on the patient sample,” says GlaxoSmithKline’s Martin. There is more. “We’re talking about cancer now, but the concept will apply to other diseases as well,” says Cecilia Schott, head of personalized healthcare business development at the London-headquartered AstraZeneca. “There are still some technical and regulatory challenges, but we’re seeing things move very fast, and it’s changing the way we’re doing drug development.” Both consortia are open to additional pharma partners. But regardless of whether further companies join either effort, eventually each should benefit the broader drug devel1074
Box 1 Who’s in the ‘universal’ companion diagnostic race The quest for a ‘universal’ diagnostic pits two heavyweight NGS platforms against one another. Thermo Fisher will use its Ion Personal Genome Machine sequencing platform combined with Ion AmpliSeq technology. Illumina will use its MiSeqDx platform, which in November 2013 became the first (and still only) FDA-approved NGS platform (Nat. Biotechnol. 32, 111–112, 2014). Illumina’s earlier approval may give it an advantage, say observers, but just as likely it has smoothed a regulatory pathway for future NGS entrants. The tests that may soon emerge are at least four years in the making following a series of strategic alliances. The NGS technology residing at Life Technologies comes from its 2010 takeover of Ion Torrent. In October 2012, the company acquired Compendia, an oncology content business where Rhodes (now at Thermo Fisher) was a co-founder. Then in 2013, Life Technologies was acquired by Thermo Fisher for about $15 billion. “From my perspective the whole motivation of merging into Life Technologies was to take our understanding of the cancer genome and of biomarkers and partner with colleagues at Life with the Ion Torrent and AmpliSeq platforms to build toward this universal companion diagnostics strategy,” says Rhodes. Illumina’s NGS technology was also bolted on through the 2006 takeover of Solexa. Also important to the advancement of its universal diagnostic was the July 2014 acquisition of Myraqa, a regulatory consulting firm with a specialty in in vitro diagnostics. “Doing this Myraqa acquisition was an enormous help to us,” Illumina CEO Jay Flatley said during a session at the September 9 Morgan Stanley Healthcare Conference in New York. “The Myraqa team will work with Illumina and also our partners to help put next-generation sequencing products through the FDA on our platform.” CM
opment community as the universal tests hit the market. “Every pharma company has their favorite gene list and most likely 80% will overlap,” says Schott. Janssen’s Dracopoli notes that although companies outside the consortia may eventually benefit from using these tests, the first partners get the benefits of early access and a seat at the table in choosing which genes are selected for testing. The pharma companies involved in both efforts describe the two endeavors as complementary, noting that different laboratories will have different preferences in terms of which NGS platform they wish to use. “Even if a particular NGS technology is perfect,” the diagnostic provider “may not have the market access or geographic reach you need, so working with only one company could be boxing your drug out of a particular market if it’s linked to a particular test,” says Kristin Pothier, partner and managing director for life sciences in transactions advisory services at Ernst & Young in Boston. “It’s in pharma’s interest to do their diligence and strike deals with several companies.” A universal test could help provide an opportunity to capture more of the combined drug-diagnostic value than has been possible until now. “I think the paradigm is shifting,” says Rhodes. “You could imagine a world
where every cancer patient [was] typed with a universal companion diagnostic that creates specific drug development opportunities in those defined segments. That standard does not exist today.” Neither NGS company would comment on its IP strategy, though multiple sources at pharma companies acknowledge that pulling together the rights for each marker—which often reside at academic centers, diagnostics companies or clinical laboratories, through a variety of exclusive and nonexclusive arrangements—will give companies plenty to think about and negotiate over. That said, there’s something inexorable about the move toward a universal test. “It will be cheaper and more effective to have tests done as part of a panel, and inevitably the world is moving toward panels. No lab wants to end up having to buy ten individual companion diagnostic tests approved by FDA,” says Dracopoli. That is behind the success of laboratory services like Foundation Medicine’s Foundation One panel, with which new universal diagnostics may compete, and demonstrates the “strong desire to simplify the testing, the guidance and the feedback for patients and physicians based on those results,” he says. Chris Morrison Yardley, Pennsylvania
Correction In an August 2014 news brief (Nat. Biotechnol. 32, 704, 2014), the dosage interval for Eloctate was incorrectly listed as ten days. The correct dosage interval is every three to five days based on clinical response. The error has been corrected in the HTML and PDF versions of the article.
volume 32 NUMBER 11 NOVEMBER 2014 nature biotechnology
Two consortia set up in recent weeks aim to create centralized cancer diagnostics that can be used to guide therapeutic decision making. On August 21, San Diego-based Illumina teamed with AstraZeneca, Janssen and Sanofi to work on an oncology test that can simultaneously analyze multiple genes and variants from a single tissue sample. Underpinning the effort, Illumina said on September 8 it had created the Actionable Genome Consortium with the Dana Farber Cancer Institute, the Fred Hutchison Cancer Research Center, the MD Anderson Cancer Center and the Memorial Sloan Kettering Cancer Center to support the use of NGS in clinical oncology practice. On September 25, Carlsbad, California–based Thermo Fisher Scientific announced a similar plan, working with GlaxoSmithKline and Pfizer, to develop its own universal companion diagnostic, based on markers from its Oncomine Cancer Research panel. “With NGS there’s an unprecedented ability to do multi-analyte analysis, and the cancer community has begun applying it to analyze tumors,” says Naomi O’Grady, senior manager, product marketing for oncology at Illumina. “Moving [a universal test] forward as a companion diagnostic emerged quite naturally,” and will make it easier for pharmaceutical companies to bring targeted therapies to market, she says. The advantage of a univer-
Dow’s newly approved Enlist fights superweeds The Environmental Protection Agency gave Dow AgroSciences final approval on October 15 to commercialize its Enlist Duo herbicide. The new system will be sold in combination with corn and soybean plants genetically engineered for plant-optimized aryloxyalkanoate dioxygenase gene from plant soil bacterium Sphingobium herbicidovorans to tolerate Enlist, which were approved on September 17, 2014. Dow AgroSciences, a unit of Dow Chemical, said the biotech crops could be available for the 2015 planting season. The Indianapolis-based firm developed the herbicide in response to weedresistance problems resulting from the heavy use of the Roundup Ready system developed by Monsanto. The new herbicide is a blend of 2,4-d choline with glyphosate, the main ingredient in Roundup. Dow expects Enlist to be an effective tool to manage glyphosate-resistant weeds.
sal companion diagnostic is straightforward. As opposed to the one-biomarker, one-test approach—the way companion diagnostics have been developed thus far—a universal test allows researchers or clinicians to look at many different genes and mutations in a single sample. This reduces the amount of often painful- or difficult-to-obtain biopsy tissue needed, and provides much more actionable information to oncologists more quickly. “It’s become obvious that a one-test, multiple-drugs solution is required and that next-generation sequencing is best suited to carry out that one test,” says Dan Rhodes, head of oncology for life sciences solutions at Thermo Fisher Scientific. Take, for example, the specific indication of non-small cell lung cancer (NSCLC), for which two approved companion tests for epidermal growth factor receptor and anaplastic lymphoma kinase mutations may soon be joined by tests for BRAF oncogene and proto-oncogene tyrosine protein kinase ROS1 mutants. There is a host of drugs, in development or approved, that target those molecular subtypes. “If you only have a small tumor sample, as is often the case in NSCLC,” says Anne-Marie Martin, head of precision medicine and diagnostics and molecular medicine for the oncology therapy area at London-based GlaxoSmithKline, it creates a challenging situation for patients and physi-
J&J buys antiviral firm Alios Johnson & Johnson of New Brunswick, New Jersey, has snapped up Bay Area-based Alios BioPharma for $1.75 billion in cash. Founded in 2008 by three executives from InterMune, Alios had previously raised $73 million primarily from corporate venture capital arms Novo Ventures, SR One, Roche Venture Fund and Novartis Ventures. The company’s pipeline includes AL-8176 to treat respiratory syncytial virus and the nucleotide NS5B polymerase inhibitor VX-135 for the treatment of hepatitis C virus infections, both in phase 2 trials, as well as several preclinical compounds.
“The lack of a viable model for Alzheimer’s has been the Achilles’ heel of the field.” P. Murali Doraiswamy, an Alzheimer’s researcher at Duke University, commenting on the recent report of a culture model for Alzheimer’s disease that recapitulates the human disease. (The New York Times, 12 October 2014)
© K.C. Alfred/U-T San Diego/ZUMA Wire
npg
© 2014 Nature America, Inc. All rights reserved.
Illumina, Thermo Fisher build consortia to develop ‘universal’ cancer tests
Illumina’s CEO Jay Flatley is driving the sequencer supplier’s business strategy in the clinical space.
nature biotechnology volume 32 NUMBER 11 NOVEMBER 2014
“Thankfully, venture funders are starting to invest again in real, hard-core science and innovation.” John Sorenson, CEO of agbiotech Vesteron of Kalamazoo Michigan, which is developing pesticides based on natural venoms. The company just completed its third round of venture-backed funding, during a quarter where venture capital investment in biotech is set to exceed the peak year of 2008. (The New York Times, 12 October 2014) “It’s time for the people who run the biomedical research enterprise in this country to make basic research the center of their pitch for funding. Collins had a huge opportunity to do that here, but he blew it.” Michael Eisen, objecting to Francis Collins’ scare tactics to extort more funding for Ebola research rather than for basic research, whence things like vaccines derive. (It is NOT junk, 13 October 2014)
1073
npg
© 2014 Nature America, Inc. All rights reserved.
NEWS cians as there may not be sufficient tissue to run all available tests. Given industry’s focus on targeted oncology therapies across multiple indications, “the problem will become staggering across many cancer types over the coming years,” says Rhodes. “The Illumina collaboration simplifies our process of developing companion diagnostics,” says Nic Dracopoli, head of the biomarkers group at Janssen Oncology, in Spring House, Pennsylvania. “We’ve identified genes we’re interested in, and Illumina has agreed to do the analytical development of those genes to the point we can use them in prospective clinical studies.” Illumina plans to offer its pharma partners the use of the test to support clinical validation and US Food and Drug Administration (FDA) approval in combination with their drugs at some point in 2015. Still, regulatory, intellectual property (IP) and reimbursement wrinkles remain to be ironed out before these tests are part of everyday cancer care. The kind of comprehensive approach enabled by an NGS–based universal diagnostic means every available marker can be analyzed in a standardized manner. Those markers may be clinically validated—where patients selected for a given biomarker have benefited from a particular treatment—or based only on analytical claims that feed into companies’ research or clinical development strategies (Box 1). Thermo Fisher says its diagnostic will enable simultaneous testing of single-nucleotide variants, copy number variants, gene fusions and indels across 143 unique cancer genes. Among the genes in the new panel, 26 are targeted by oncology drugs currently on the market, and an additional 44 are used in determining eligibility for current clinical trials. The test is expected to look at about 3,000 total alterations. “The beauty of this panel is that some of the work we would have done retrospective to a study we can now do prospectively. Beyond patient selection, this approach allows us to generate more comprehensive molecular information on the patient sample,” says GlaxoSmithKline’s Martin. There is more. “We’re talking about cancer now, but the concept will apply to other diseases as well,” says Cecilia Schott, head of personalized healthcare business development at the London-headquartered AstraZeneca. “There are still some technical and regulatory challenges, but we’re seeing things move very fast, and it’s changing the way we’re doing drug development.” Both consortia are open to additional pharma partners. But regardless of whether further companies join either effort, eventually each should benefit the broader drug devel1074
Box 1 Who’s in the ‘universal’ companion diagnostic race The quest for a ‘universal’ diagnostic pits two heavyweight NGS platforms against one another. Thermo Fisher will use its Ion Personal Genome Machine sequencing platform combined with Ion AmpliSeq technology. Illumina will use its MiSeqDx platform, which in November 2013 became the first (and still only) FDA-approved NGS platform (Nat. Biotechnol. 32, 111–112, 2014). Illumina’s earlier approval may give it an advantage, say observers, but just as likely it has smoothed a regulatory pathway for future NGS entrants. The tests that may soon emerge are at least four years in the making following a series of strategic alliances. The NGS technology residing at Life Technologies comes from its 2010 takeover of Ion Torrent. In October 2012, the company acquired Compendia, an oncology content business where Rhodes (now at Thermo Fisher) was a co-founder. Then in 2013, Life Technologies was acquired by Thermo Fisher for about $15 billion. “From my perspective the whole motivation of merging into Life Technologies was to take our understanding of the cancer genome and of biomarkers and partner with colleagues at Life with the Ion Torrent and AmpliSeq platforms to build toward this universal companion diagnostics strategy,” says Rhodes. Illumina’s NGS technology was also bolted on through the 2006 takeover of Solexa. Also important to the advancement of its universal diagnostic was the July 2014 acquisition of Myraqa, a regulatory consulting firm with a specialty in in vitro diagnostics. “Doing this Myraqa acquisition was an enormous help to us,” Illumina CEO Jay Flatley said during a session at the September 9 Morgan Stanley Healthcare Conference in New York. “The Myraqa team will work with Illumina and also our partners to help put next-generation sequencing products through the FDA on our platform.” CM
opment community as the universal tests hit the market. “Every pharma company has their favorite gene list and most likely 80% will overlap,” says Schott. Janssen’s Dracopoli notes that although companies outside the consortia may eventually benefit from using these tests, the first partners get the benefits of early access and a seat at the table in choosing which genes are selected for testing. The pharma companies involved in both efforts describe the two endeavors as complementary, noting that different laboratories will have different preferences in terms of which NGS platform they wish to use. “Even if a particular NGS technology is perfect,” the diagnostic provider “may not have the market access or geographic reach you need, so working with only one company could be boxing your drug out of a particular market if it’s linked to a particular test,” says Kristin Pothier, partner and managing director for life sciences in transactions advisory services at Ernst & Young in Boston. “It’s in pharma’s interest to do their diligence and strike deals with several companies.” A universal test could help provide an opportunity to capture more of the combined drug-diagnostic value than has been possible until now. “I think the paradigm is shifting,” says Rhodes. “You could imagine a world
where every cancer patient [was] typed with a universal companion diagnostic that creates specific drug development opportunities in those defined segments. That standard does not exist today.” Neither NGS company would comment on its IP strategy, though multiple sources at pharma companies acknowledge that pulling together the rights for each marker—which often reside at academic centers, diagnostics companies or clinical laboratories, through a variety of exclusive and nonexclusive arrangements—will give companies plenty to think about and negotiate over. That said, there’s something inexorable about the move toward a universal test. “It will be cheaper and more effective to have tests done as part of a panel, and inevitably the world is moving toward panels. No lab wants to end up having to buy ten individual companion diagnostic tests approved by FDA,” says Dracopoli. That is behind the success of laboratory services like Foundation Medicine’s Foundation One panel, with which new universal diagnostics may compete, and demonstrates the “strong desire to simplify the testing, the guidance and the feedback for patients and physicians based on those results,” he says. Chris Morrison Yardley, Pennsylvania
Correction In an August 2014 news brief (Nat. Biotechnol. 32, 704, 2014), the dosage interval for Eloctate was incorrectly listed as ten days. The correct dosage interval is every three to five days based on clinical response. The error has been corrected in the HTML and PDF versions of the article.
volume 32 NUMBER 11 NOVEMBER 2014 nature biotechnology
