Mara Aspinall, president of Ventana Medical Systems Inc
With the increasing prevalence and importance of personalized medicine, so too comes a rise in the use of companion diagnostics, assays used to identify specific protein and genetic makeups that indicate the optimal therapeutic treatment for a patient. Ventana Medical Systems Inc, Tucson, Ariz, a member of the Roche Group, has recently initiated companion diagnostic product developments in partnership with companies ranging from Bayer to Pfizer. Clinical Lab Products sat down with Mara Aspinall, president of Ventana, to discuss these new offerings and the companion diagnostics industry as a whole.
CLP: Give us some background on companion diagnostics.
Aspinall: Let me start with the FDA definition. A companion diagnostic is a medical device that identifies or determines a condition of use for a therapeutic product, and is important to ensure the safe and effective use of that product. Essentially, it is as descriptive as it sounds. It really is something that refines the diagnosis in a way to get the data to drive the use of the most likely for success therapeutic intervention.
CLP: How did companion diagnostics hit the market?
Aspinall: You can look at this two different ways. Most people give credit to HER2 and Herceptin as the first companion diagnostic, where the original Herceptin proposal to the FDA was not approved even though a relatively small percentage of the patients responded and responded very well. Nobody at the time knew why lots of other patients did not respond. The company said, “Let’s figure out more about why those 10% responded.” The answer was that they have a gene for HER2 and had an overabundance of expression of that gene. Therefore, once you have that overexpression, you’re more likely to respond.
I think that’s the contemporary definition. I think it was starting much before that on a much more basic level. If we stick with breast cancer, if patients were estrogen-receptor positive, they were given hormone-based treatment, hormone modulators—tamoxifen and its precursors. That is personalized medicine as well, but not really considered personalized medicine. It was taken for granted that once we know that information, we treat the patient a specific way.
Herceptin and HER2 was the first one that was FDA-approved and was much more targeted: if you have this overabundance of this particular gene, you take this particular drug. I consider personalized medicine even broader. AIDS patients, at least in the developed world, see their physicians typically every quarter. As they do that, they are getting information on viral load and virus genotyping. That’s personalized medicine. Once the doctor has that information, they adjust the dose and adjust the medication that that patient is given.
CLP: Do you have to develop a specific companion diagnostic for each therapeutic treatment?
Aspinall: Probably. Zelboraf, a newly approved drug for malignant melanoma, works in roughly half of the melanoma patients. That is an example where, at the same time that the FDA approved the drug, they also approved a test for BRAF, a particular mutation called V600E. If you have that mutation, you are likely to be one of the people that responds to Zelboraf. If you don’t, you are highly unlikely to respond to the drug. That is a classic definition and one that’s been very interesting because it has had an FDA approval of the drug and the test together. But, there are broader tests like the mutation tests for EGFR or KRAS that may indicate that a patient is likely to respond to a class of drug, such as EGFR inhibitors. Sometimes it’s specific like BRAF and Zelboraf, and other times it’s broader and with the test, you are looking to a response for a type of drug or class of drug, not necessarily one specific drug.
CLP: Why did Ventana choose to collaborate with the various developers for the recent companion diagnostic tests?
Aspinall: We have a broad array of tissue-based technology that is attractive for pharma companies, particularly in oncology, that are looking to create assays based on those technologies. This has changed over the last few years because pharma developers have done a great job understanding the mechanism of action of a particular drug. Roche has technologies including molecular diagnostics and immunoassays that are also important companion tests. Once you understand the mechanism of action, it’s much easier to then recognize, “With that mechanism, we need to see if this protein or gene exists.” We can do that through immunohistochemistry tests. We can do that through in situ hybridization tests. Our colleagues can do this through molecular tests. We develop those tests for those pharma on a cost-effective basis so that we can move that forward. We have the technology, development expertise, and regulatory expertise … so it gives us a broad range of technologies to truly be technology agnostic. Whatever the pharma wants to focus on, at Roche we have the ability to help them focus on it. In oncology, there has been a large level of interest in tissue-based tests and tissue-related tests, and that’s our sweet spot.
CLP: What tests did you develop the companion diagnostics for? Why did you choose these?
Aspinall: We can only discuss those projects in which our partner has agreed to discuss publicly. For Pfizer, we announced a test related to the ALK gene for non-small cell lung cancer. For Bayer, we announced an assay but did not say the name of the biomarker or the name of the drug, so I can’t release any more. For Syndax, we are also working in non-small cell lung cancer, and the diagnostic is supporting their drug Entinostat.
CLP: Do companion diagnostics have any application outside of personalized medicine?
Aspinall: In my mind, it’s hard to define because they’re very much interrelated. Personalized medicine is bigger than companion diagnostics. Personalized medicine is getting additional information to target the therapeutic intervention. Companion diagnostics is a subset of that.
Take blood cancers as an example. One hundred years ago, all we knew was that there was lymphoma and leukemia. Today, there are hundreds of different types of leukemia and lymphoma. We can get the diagnostic very specific for personalized medicine, but not all of those today have different drug regimens because they haven’t been invented yet. So all personalized medicine tests might ultimately be a companion diagnostic, but probably not.
Increasingly, we’re finding that even treatment paradigms—whether you go to surgery or not—may be personalized, that patients with a certain mutation are likely to respond to a certain surgical intervention. That might be considered a companion diagnostic. Take weight-loss surgery; there’s now some thought that certain people respond to weight-loss surgery as opposed to others. It may be based on a gene mutation that they have versus others who don’t have that mutation. That’s personalized medicine. You could debate whether or not it’s companion diagnostics.
CLP: Why hasn’t the rise of companion diagnostics directly mirrored that of personalized medicine?
Aspinall: Firstly, companion diagnostics takes two to tango. What companion diagnostics needs is pharma or biotech—basically, the drug developers—to be part of the companion diagnostics program. Without the drug developers being part of the program, there is no true companion. I do believe that it’s mirroring PM, but it’s just a little lagging. What we have seen in the last 3 to 5 years is a tremendous rise in the amount of interest and focus on both personalized medicine and companion diagnostics.
Ten years ago, many pharma didn’t acknowledge the importance of companion diagnostics. Five years ago, they acknowledged it. And in the last few years, they’ve proactively said, “We’re not going to wait until the FDA says we need a companion diagnostic. We’re going to go after that now and start our diagnostic program at an early stage of our drug development.” In the broadest way, it’s mirroring the growth of personalized medicine, but it’s a lagging indicator because pharma and biotech had to get comfortable and get their arms around changing their business model to include a diagnostic as a piece of it.
CLP: Is there a reason there was any resistance?
Aspinall: You’d have to ask them, but I think there was a perception that it would narrow their market. Some of the data may imply that a companion diagnostic may narrow it in some ways, but it will expand it in many more, including better compliance from patients, better compliance from physicians, and the fact that there are likely to be more people diagnosed with a particular subset of a disease than expected.
The other initial concern is that diagnostics and pharmaceuticals are very different markets and the regulatory uncertainty made Pharma concerned, and, I think, quite legitimately. They were forced to say, “What does this mean? How do we market it? Does this change our label?” The FDA has really tried to be very helpful in clarifying the rules around this with guidance on companion diagnostics.
At the same time, particularly of late, the FDA has insisted that a companion is created. They have tried to bring these two areas together, but just like all new technologies, the technology got ahead of some of the infrastructure in the industry and we needed to catch up to ensure that companion diagnostics and the regulatory environment was indeed a benefit for patients. The FDA was quite thoughtful in working with industry stakeholders to create those new guidelines.
CLP: So you would say that the industry will continue the trend of companion diagnostics?
Aspinall: Absolutely, and not only have we seen the tremendous interest here at Ventana and at all of Roche Diagnostics, but I think that there’s a new philosophical approach among pharma companies where they are now going into their development plans—and they’ve shared this publicly—with the thought, “How do companion diagnostics fit into our overall plan?”
CLP: Do you think more companies will begin codeveloping companion diagnostics with therapeutics?
Aspinall: I do, and I think it will be looked at as a competitive advantage. It would be looked at as a way to differentiate your drug and make it more cost-effective and appropriate for the target population.
CLP: Does Ventana have any plans to develop more companion diagnostics in the future?
Aspinall: Absolutely. We have a number of programs. First, we hope to be the partner of choice for Pharma and continue closing more partnerships. Some of them we announce publicly. Others we won’t be able to announce publicly, and that’s really up to the drug developers. We will continue to support this aspect of our business.
Secondly, and very critically, we at Roche have six compounds that are in late-stage development with companion diagnostics associated with them, with multiple of these utilizing Ventana companion diagnostics. One other that was recently launched was Zelboraf, launched along with its Roche Diagnostics companion diagnostic BRAF mutation test. We’ve also got a number of early-stage programs. We see it as an exciting, growing, and most importantly, critical area for patients.
CLP: Is there anything else you’d like to add?
Aspinall: We believe that companion diagnostics is a global trend and not something that’s specific for any one market or any one health system. It is something that is key to the world and in many ways, even more critical in the areas where the drug supply is not always as robust as in the US. Companion diagnostics allows physicians to use those valuable assets that they have in a much more focused way than what we’ve called in the past, trial and error medicine. We do believe that it’s a win for the patient and a win for health care systems. We want to help enable that.
Chris Gaerig is CLP’s associate editor.
