A Feburary 7th article in the online version of Nature magazine began with the line, "Genomics finally came of age as a clinical discipline on November 19, 2013, when the US Food and Drug Administration (FDA) approved Illumina's MiSeqDx next-generation sequencing (NGS) system for clinical use."
Now, some may argue with this and say genomics was coming of age with the BRCA test from Myriad back in the nineties, or with the use of NGS for cancer treatment, or the rise of prenatal diagnostics.
And some may say that the science just isn't here yet. There are very few applications. I was talking recently with a member of the team at Health and Human Services last week who helped draft Obamacare. She said that most folks in healthcare and most of congress is certainly not aware of KRAS, BRAF, EGFR, etc. The science is very new and there must be many many more clinical trials. Furthermore, we've inherited a healthcare system that was designed for infectious diseases and lacks the infrastructure and expertise in molecular medicine.
But we can all agree that the clearance by the FDA of an NGS platform is a milestone and goes another step to fulfilling the promise of genomic medicine that began many years ago.
Last week, I moderated a panel discussion, “The Clinical Sequencer,” at Select Bio’s conference in San Diego, NGS: Research to Clinic. Daniel Grosu, VP of Clinical Development and Medical Affairs at Illumina, played a large role in getting the MiSeqDx platform FDA approved. He joined us on the panel among with a terrific lineup of four other experts in the space. I think highlights of their comments deserve to be written down.
Daniel Grosu, VP Clinical Development and Medical Affairs, Illumina
Daniel was brought on at Illumina in 2011 as their first Chief Medical Officer (a position which is now filled by the former head of the NCI, Rick Clausner). Daniel said that the process of getting approval for MiSeqDx took about eleven months total. Because the FDA had not approved anything like this before, they had to figure it out as they went along. For example, PCR and Sanger sequencing were used to verify the quality of the Illumina NGS platform, even though neither of these technologies have FDA approval in this particular context.
Daniel was keen to explain that there were really two approvals at the FDA. One was for the MiSeqDx Cystic Fibrosis Assay and the other was for the open platform with reagents.
He also confirmed that Illumina is actively seeking big pharma partnerships for CoDx development with the now approved platform. Earlier this year Illumina announced that they would be collaborating with the biotech giant, Amgen, to develop an NGS-based companion diagnostic for their colorectal cancer drug, Vectibix.
Hakan Sakul, Executive Director and Head of Diagnostics at Pfizer
Another one of those partners might be Pfizer, who’s Head of Diagnostics, Hakan Sakul joined us on the panel. Of course Hakan wouldn’t verify wether Pfizer is partnering yet with Illumina on the newly approved platform, but he said that he’s very excited about the opportunities with NGS. Hakan said that NGS provides some clear advantages over PCR and earlier in the day he even mused about whether NGS would replace PCR.
Hakan pointed out that clinical sequencing offers clinicians the opportunity to do research and medicine at the same time. With a PCR test you have to know what you’re looking for, but NGS provides a more robust tool for discovery. This will be a challenge for regulators, Hakan said. So far to get a diagnostic test approved by the FDA, a company like Pfizer has to choose a target, or panel of targets, which are spelled out as part of the test. He left the question open as to how a regulator goes about approving a test where the specific target is yet to be discovered.
Shawn Baker, CSO, AllSeq
Shawn Baker keeps track of all of NGS platforms--new, old, and upcoming--for the neutral sequencing marketplace, AllSeq. As a panelist he said he had more questions for the others than answers. He asked Daniel Grosu about the tension that is sure to arise at Illumina now that they have a MiSeq for research and one for the clinic. These are two very different markets. The research market accepts and expects constant innovation and upgrades, where the clinical market must have a platform which is stable.
Daniel confirmed that these markets were different, but said that there is opportunity to improve the clinical platform with regular upgrades. He said that Illumina wouldn’t slow down in providing the research market with continual innovation.
I asked Daniel if Illumina planned to make a platform expressly for the clinic. “The MiSeq,” he replied.
Nazneen Aziz, Director of Molecular Medicine, College of American Pathologists
Our fourth panelist, Nazneen Aziz of the College of American Pathologists, or CAP, has been pioneering the standards for NGS that will be necessary in pathology labs. She said that her team at CAP is not so much focused on the instrument--it doesn’t matter what platform a lab uses--or the bioinformatics software, as much as whether the lab tech can call the disease variant correctly. As part of the testing, Nazneen and her team have the lab sequence a known genomic segment and call the variants. This is then compared to CAP's own gold standard for which they used various NGS platforms, including Illumina and Complete Genomics.
CAP testing also includes a profiency test for the lab techs. Nazneen says that most pathology lab techs are sufficiently qualified to use an NGS platform.
Nathan Pearson, Genome Scientist, Ingenuity/Qiagen
It appears that Illumina will soon have some competition with their MiSeqDx platform. Qiagen has announced their own clinical NGS platform, the GeneReader, to be commercialized later in 2014. (Stay tuned for our interview with Dietrich Hauffe, VP of Life Science at Qiagen to be published next week.)
Our fifth panelist, Nathan Pearson, has been working in bioinformatics at Ingenuity Systems. The company was bought last year by Qiagen. Nathan said he couldn’t say much about the GeneReader yet, but confirmed that yes, it would come out in 2014. Qiagen has worked with the FDA for many years and boasts an impressive lineup of approved diagnostic kits. With an NGS instrument along with their sample prep kits, their PCR kits, and their newly acquired bioinformatics assets (they also bought CLC Bio last year), Qiagen is set to have an impressive end-to-end workflow to offer clinical labs. Controlling the entire workflow will give Qiagen the opportunity to raise the standards for clinical sequencing. Now the process is very modular with lab techs using various suppliers for different steps.
I asked Nathan how will we know when a bioinformatics platform is robust enough. He replied that "it’s like the early days of the computer. Were they ever good enough? No. But did they help out a lot? Yes." Nathan said that we are still a long ways away from knowing what to do with “the genome.” He said that when a healthy person gets their genome sequenced it might not do much for them now, but it can do a lot for biomedical research. He encouraged everyone in the room to get their genome sequenced and donate it to research.
Clinical sequencing is a very exciting and fast changing space. In a year or two from now there could very well be other players who we don’t mention today, someone with a disruptive technology.
No matter what whiz bang clinical sequencing technology that comes along, there is a big challenge that remains for the business model of diagnostic companies. Diagnostics are just not valued highly like therapeutics.
I've heard from industry leaders that someday we'll be saying CoRx, that the value will be in the Dx side and the Rx will supplement that. But we're a long ways from that today. In fact, the price for Dx continues to drop. Myriad, since the Supreme Court decision on gene patents, has faced a drop by half of their reimbursable price. Why is it we don't want to pay for the tests that diagnose a disease? They cost a lot of money to develop. (It’s not as costly as developing a therapeutic, but it is very high--in the hundreds of millions.) Is it a cultural issue? We don't value naming a problem like we do the solution? I left the panel with this open question: What is the biggest barrier to raising the value of diagnostics?