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Q&A: Foundation Medicine's Vincent Miller on Providing Knowledge to Oncologists

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miller.jpgName: Vincent Miller
Age: 50
Position: Senior vice president, clinical development, Foundation Medicine, since 2011
Experience and Education:
Attending physician, Memorial Sloan-Kettering Cancer Center, 1994-2011
Fellow, medical oncology, Memorial Sloan-Kettering Cancer Center, 1991-94
Chief medical resident, internal medicine, Thomas Jefferson University Hospital, Philadelphia, 1990-91
MD, University of Medicine and Dentistry of New Jersey, 1987
BA in mathematics, University of Pennsylvania, 1983

Vincent Miller became Foundation Medicine's senior vice president for clinical development last fall. He joined the company from Memorial Sloan-Kettering Cancer Center in New York, where he was an attending physician specializing in lung cancer.

Clinical Sequencing News spoke with Miller last week about his move; the "soft launch" of Foundation Medicine's comprehensive cancer genomics test, which it plans to launch nationwide around the middle of this year; and its alliances with pharmaceutical companies. This week, Foundation Medicine announced that its genome sequencing laboratory in Cambridge, Mass., has obtained CLIA certification. Below is an edited version of the conversation.



Why did you join Foundation Medicine after almost 20 years at Memorial Sloan-Kettering Cancer Center?

To be honest, I never thought I would leave. I had the privilege to work early on with a drug called Tarceva, or erlotinib, its generic name, and see the inexorable linkage between EGFR mutations and response to that drug. I was in the right place at the right time in the sense that we were one of the first groups to describe that mutation and that association, and then we went on to show that there were second-site mutations that arose that mediated resistance. And when one sees something like that firsthand as a treating oncologist, it just brings things to a new level, and to me, it clearly showed that this was the way forward to improve outcomes for our patients.

Shortly after that, a group of colleagues and friends and revered cancer biologists announced they were starting Foundation Medicine, and at some point, a mutual contact introduced us and I became enamored that the vision was quite in line with mine, that this was a way for me to reach and help more patients and doctors more quickly than I could do even in a wonderful place like Memorial Sloan-Kettering.

Could you provide an update on the commercialization of Foundation Medicine's comprehensive cancer genomic test?

Obviously, much of it was initiated and the groundwork laid before I started at FMI. We have obtained our CLIA certification and have begun accepting clinical samples and reporting out results. We have been impressed that we have received a far greater than anticipated number of samples for a product that hasn't been launched yet.

These are a variety of samples. We are not talking about anything from pharma collaborations or academic medical centers; we are talking about physicians who may have heard about the test, or patients who heard about the test and asked their doctors to order it. These are sort of run-of-the-mill sources, and that's great. That's what we want to become, a tremendous help in improving cancer outcomes.

What needs to be done before the official launch of the test later this year?

I don't know that there is one explicit event or process that needs to occur. I think it's really vetting any issues or problems that arise as a new process is begun; it's been going quite smoothly. Certainly, each time we analyze a patient's tumor, there is the potential for identifying a novel mutation, or a novel combination of mutations. So each report we generate and each communication to the doctor is a little bit different.

I think at some point, we'll start to see certain repetitive patterns and some cases will be easier to complete, but right now, it's tremendously exciting in the sense that when those results come off the sequencer, we never quite know what to expect, and we really had some enlightening cases that we hope to be able to share with larger scientific audiences or in peer-reviewed publications imminently.

How has the test changed since the company first presented it last year?

Certainly over the course of the year, the amount of DNA required to reliably provide results has dropped significantly. The number of genes in the test has increased significantly, from 140-some now to more than 200. Our content is under constant review, internally, in concert with reviews with our founders, and with various databases and literature searches, to make sure that we have the most contemporary and comprehensive genomic profile available for clinical use.

[The test still runs on the Illumina HiSeq, but] we're always open to improvements in technology. We are not married to any particular platform. We're married to what we think helps the most doctors and the most patients on limited tissue sources in a timely fashion.

How is the company's data-reporting platform and physician interface progressing?

Currently, the reports are populated with information we have about the genomics of the particular aberrations, whether approved therapies are available for that aberration, what clinical trials might be available, or at least a sampling of them, arbitrarily identified. The reports are either faxed or mailed to the physician. Certainly early on, we are trying to routinely follow up those reports with a call to the ordering clinician, both to go over it content-wise but also to see if he or she has any recommendations on how we can make things better. So far, our feedback has been really positive.

What's the price and the current turnaround time of the test?

At $5,800, the list price of Foundation Medicine’s test is in line with other highly complex molecular diagnostics on the market today.

Our goal is on commercial launch to have a turnaround time of 14 days in the vast majority of cases. I think early on, in part because we are learning and trying to do the reports and get those pieces in place as far as content, it is a little bit longer than that, but I think there has been generally wide acceptance and satisfaction on the treating clinician's part. I have not been aware of any daily calls, 'Where is the report? It was promised a week ago,' but rather, many people have been pretty pleased that we have been real close to our goals, if not meeting or exceeding them.

Have any of the samples you have so far analyzed been reimbursed by insurance yet?

We are actively working on our reimbursement strategy. Like with any new test, it will take time and appropriate clinical studies to convince payors this is the right approach long-term. We have already initiated discussions with third-party payors and we have had our first conversation with the Centers for Medicare and Medicaid Services as well.

Other places, both academic centers and companies, have recently developed targeted sequencing panels for cancer. How do you distinguish yourselves from these at Foundation Medicine?

There are a number of components to that. One is, I still think we have the most comprehensive genomic profile for clinical use. There have been papers published recently that might have looked at various platforms that are in theory more encompassing than ours, but any of the key genomic events identified would have been found by our test, and that was very reassuring and satisfying to us.

Another really nice thing about the group here, in particular folks like myself who have been in the trenches, [is that] we are particularly sensitive to the challenges of medical oncologists working in non-tumor-type-specific practices, trying to take care of patients with breast cancer, colon cancer, lung cancer, prostate cancer, et cetera, and who are trying to stay abreast of the landslide of molecular information coming down upon them. To that end, one of the nice things about the test is that it is indeed a pan-solid-tumor test. They can check a box, and don't need to be on the top of their game trying to remember if they should order a [test for] mutation X in colon cancer, or if that was only for lung cancer.

Another thing that's really exciting is that the test does not require dividing limited tissue resources into multiple sections or subsections for different types of testing. When I worked with a Sequenom-based test, we had to parse out enough tissue slides to do testing for certain copy number gains or amplifications in genes that were commonly perturbed in lung cancer. With our platform here, we can detect multiple classes of alterations in the one test and the one tumor sample: copy number alterations, insertions/deletions, rearrangements, in addition to point mutations. The breadth of that, and doing the same test across diseases, is a highly powerful vehicle for discovery, and to me as a scientist, not someone with a diagnostics background, the discovery is an incredibly seductive and exciting aspect of what we think about and talk about every day in the halls here.

Can you outline how the test might develop over time? Are you planning to include other types of analyses, like gene expression, epigenetic, or proteomic analyses? How important do you think these will be?

My succinct answer is 'yes,' but what I would also say is that our first mission is to scale up and execute on our DNA platform. And then we will continue to do pilot studies involving many of the technologies to which you alluded, because we envision that, although many answers come from a DNA platform, they will need to be complemented with other components to fully elucidate the spectrum of genomic changes, not only across solid tumors but also across liquid tumors. To be an end-to-end solution provider in oncology, we will require something beyond this critical DNA piece, and we are constantly positioning and reassessing ourselves to look at how we can be ready to go when someone approaches us with a proposal that we think is scientifically rigorous or robust or attractive.

Some institutions and companies today bet on whole-genome or whole-exome sequencing rather than targeted sequencing to analyze tumor samples. There seems to be two schools of thought on that. What do you think about that?

Our content is constantly updated to include any genes known to be somatically altered in human cancer … and to date, there has been little if no add when one looks across studies of whole-exome sequencing or whole-genome sequencing that have been done. In fact, we think any theoretical gain in content is probably more than offset by the tremendous coverage we have, which is really unprecedented. We have 99 percent sensitivity to detect genomic events that are present in more than 5 percent of alleles. That speaks to the clinical need of specimens obtained from real patients often being admixed with inflammatory cells, adipose tissue, blood, ploidy issues, clonal issues, et cetera. In addition, I think that [other] platforms, such as [the ones] you mentioned, continue, although the sequencing time is driven down, to be rate limiting around the computational biology piece, which is really the special sauce in part of the test we're offering. The algorithms we have developed here are really exceptional.

Speaking as a clinician, what percentage of cancer patients do you think can directly benefit from Foundation Medicine's test today? Also, does that depend on the type of cancer they have?

We have not studied every solid tumor type available; we hope to get our hands on them. That being said, I would be hard pressed to find a situation in which I would not want this test performed. At the very least, it will give the treating oncologist the feeling that he or she maximally explored the potential knowledgebase around the tumor, and beyond that, the potential upside, as far as identifying genomic changes that less sensitive platforms would [also] have detected, or ones that were not even in other platforms and that can result in a therapeutic success, either through a drug approved in another indication, [or] a phase II or III clinical trial. When I see a report that adds something to the knowledgebase for a treating physician, particularly when there maybe is a clinical trial in the area, or the physician has such a trial himself, that really gives hope to everyone.

Specifically around the setting of phase I clinical trials, where therapy was often chosen empirically, the historical response rates are really low. There was preliminary data last year at [the American Society of Clinical Oncology annual meeting], and we hope to see more data from ourselves in the not-too-distant future, that our type of testing can greatly enhance the efficacy results [of phase I clinical trials].

Can you provide an update on your collaborations with pharmaceutical companies?

As you may know, we have five announced partnerships with large pharma [Sanofi, Johnson & Johnson, Novartis, Celgene, and an undisclosed firm] and hope to have more to share and discuss with you in the not-too-distant future. Each arrangement is a little bit different. For example, in some settings, we are prospectively analyzing tumor samples to determine whether a patient's profile of genomic alterations makes them eligible for a clinical trial of a targeted therapy.

A second type of analysis has been to analyze samples from trials that either failed to meet their primary endpoint or met their primary endpoint, but the efficacy impact was felt to be marginal. And these are exciting because I think a lot of us believe that there are subsets of patients characterized by genomic alterations who get far greater benefits from targeted therapy than other subgroups, and we hope to be able to tease those apart, help the pharma partners develop prospective trials, validate that profile, and get the drug to patients that need it, aside from any other considerations around companion diagnostics and things of that sort.

We have also been able, with the completion of our medical team, to bring more of a balance to the pharma relationships. These are not situations where they are mailing you x specimens [and saying] 'Can you test these and send us the results back?' These are relationships often where they say, 'What do you think of this clinical trial? What do you think about our plan to biopsy these patients?' We were really partners in helping to, in many cases, drive the strategy of the trials, and hopefully, there will be a bidirectional information flow so that we can look at the data, and the patients' genomic profile, and their clinical characteristics, and how much their tumor shrank or did not shrink, and more readily develop new hypotheses around how to identify patients for drugs more quickly.

How important will these pharma collaborations be for Foundation Medicine going forward?

Although we are popular with pharma, and we have announced deals, I don't think we want to have an infinite number of partners. We want to have some really solid partners who see the vision of cancer care evolving the way we do. And in concert with that, while it will help the company financially, [limiting them] will allow us to focus on our ultimate mission, which is getting this test, this assay, to doctors and patients across the country and around the world. I don't want it to detract from our number one mission.

Is there anything you'd like to add?

It's a great culture here, and exciting to come in every day and see what one or more of us have learned that's new about cancer from developments in the last 24 hours.

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