Expanding Access to Whole Genome Sequencing Across the Globe

January 7, 2022

Illumina and the global nonprofit Genetic Alliance late last year unveiled the iHope Genetic Health program, which is aimed at providing whole-genome sequencing to patients across the globe impacted by genetic disease. At least half of iHope Genetic Health’s efforts will be focused on areas of the world in need outside the United States with more than one-third of Illumina’s support being dedicated to patients in Africa. Through the program, Illumina will enable Genetic Alliance to create networks of clinics, and laboratories equipped with the necessary genome technology to provide precision genomic diagnoses to patients suffering from rare genetic disease. We spoke to Ryan Taft, vice president of scientific research for Illumina, about the growing case for expanded use of genome sequencing as a diagnostic tool, the iHope Genetic Health program, and its efforts to expand use of the technology in low- and middle-income communities around the globe.

Daniel Levine: Ryan. Thanks for joining us.

Ryan Taft: It’s a pleasure to be here. Thanks for having me.

Daniel Levine: We’re going to talk about the growing case for making genome sequencing a standard of care within pediatric patients with signs and symptoms of genetic diseases and a recent effort by Illumina to expand the use of sequencing in middle income communities around the world. Where are we with the use of whole genome sequencing as a clinical tool and to what extent has whole genome sequencing been integrated into the healthcare system today?

Ryan Taft: It’s a great question and a great place to start. As you know, this is a topic very near and dear to my heart. I want to see every kid who needs access to this kind of technology get it. I still think we’re at the beginning phases of seeing this routinely used in the clinic. We’ve now got dozens of laboratories all over the world who have spun this up as a validated clinical test, but if we think about the total number out there in the world, somewhere between 250 million to 300 million patients with a rare and undiagnosed genetic disease, I think we’re still barely scratching the surface. So, the tools are there, the infrastructure is there, but we’re not yet there with the scale. So, if we think about this as a kind of industrialization process, we’re still at the very beginning, we’re still the very early adopters and we have yet to see mainstream adoption.

Daniel Levine: You were an author of a recent article in the Journal of Genomic Medicine that found that there’s significant underutilization of genetic testing and substantial delays for pediatric patients suspected of having a genetic disease to get testing. Can you quantify that?

Ryan Taft: Yeah. We entered this study expecting to see underutilization, but frankly I think we were shocked at the degree to which we’re seeing underutilization. We did this study using more than 13 million patients drawn from an Optum dataset. This is data provider here in the United States so this is going to be focused on U.S.-based patients. When we selected for patients with signs and symptoms of a genetic disease in this dataset, we found that depending on how we cut the data, only 4 to 8 percent of those patients had any genetic testing. And maybe to put kind of a fine point on this, we looked at patients with signs of intellectual disability, developmental delay, multiple congenital anomalies or epilepsy, and these conditions have multiple society guidelines, which indicate these patients should get genetic testing. We found that only 5 percent of those patients received any kind of molecular testing, and it took about 473 days for them to get a test from first presentation in the clinic. And here we’re not talking about getting access to whole genome sequencing. We’re talking about any genetic testing whatsoever. So, I think we can, hand on heart, say, “now that we know this patient is being undertested, these patients are not getting the diagnoses they need.”

Daniel Levine: It’s pretty astounding and distressing to hear those numbers. Why is that? Why is sequencing not more routinely used, even genetic testing of any kind, particularly pediatric patients where they’re suspected of having a, a genetic disease?

Ryan Taft: It’s a great question and I don’t think we have a great answer at this point. I can speculate that the study that we just published didn’t address why, and that will certainly be one of the next questions we have to go and investigate more closely.

Daniel Levine: What are your speculations?

Ryan Taft: Yeah, so my speculations are a few things. One, I think this does come down to reimbursement for a lot of these tests. So, is it possible for a clinician to order this test and actually have it reimbursed as we know policies across the U.S. are highly variable, they’re often difficult to manage, our system isn’t great at making sure these patients can, can get the right test at the right time from a reimbursement standpoint? The second is education and that’s at multiple levels. So, administrators in systems, making sure they understand the value of this kind of molecular testing. I think it’s very obvious sometimes to see the value of a therapy and I think it takes longer to see the value of a diagnosis. So, I think we need to continue to educate hospital administrators and other health system administrators on the value of these kinds of testing. Then there’s clinician education to make sure that they understand that these tests are going to have an impact on their patients and then there’s patients and families themselves. So, I think there’s a whole almost societal education we need to continue to do—about the value of molecular testing and a diagnosis. Go ahead.

Daniel Levine: What is the case for doing so, and is there an economic case to be made that this is not only beneficial to patients but cost effective?

Ryan Taft: I’ll take that in two parts. I think there’s what is almost the existential case for making sure these patients get a diagnosis, and the strong statement I often make is I personally have never worked on a case where providing a diagnosis didn’t have an impact on the patient or that family, you know, we’re stopping the diagnostic odyssey, stopping unnecessary testing. We’re often providing a psychological salve. We’re providing that family an answer. We’re stopping that psychological anguish. We often put these patients on the right supportive care pathway. So even if it’s not an ideological therapy that’s not going directly to the pathway, it’s providing a care pathway that wouldn’t have been available to them. And then in some cases we actually do have drugs or other therapies we can pull off a shelf that lead to dramatic quality of life changes. So that’s the kind of philosophical existential set of arguments. From a cost perspective, I think we see increasing evidence that doing, particularly whole genome sequencing, systemwide is going to be cost saving. We just saw the 100,000 Genomes Project out of gel published their first pilot set of data in the New England Journal of Medicine where they were able to show this in their rare disease population. And my colleagues here at Illumina just published a paper in Genetics and Medicine where they did a modeling exercise where they looked at both pediatric patients and neonates and they looked at standard of care testing, which would be multiple, molecular genetic tests, genome sequencing, or genome sequencing after standard of care testing. What it showed was that at worst genome sequencing is cost neutral and at best it’s likely to be cost saving. So, I think we’re seeing more and more evidence that this is the right thing to do for the patients not to just because it puts them on the right care pathway, but because it’s going to save the system money.

Daniel Levine: What do you think it would take to change that and make it more routinely used?

Ryan Taft: Yeah, it’s a great question. I think this goes back to some of the gaps we’ve talked about, right? So, we need reimbursement policies that acknowledge the need for this testing systematically. We need to increase system level education of the clinicians, the administrators, and the people who are going to be ordering these tests. We need, at least in the U.S., federal and state policies to support this kind of testing. And of course, we’ve got to continue to develop the tools that are going to make this easier. I mean, the technology’s matured at an amazing rate over the last 10 years, but I certainly want to see it get to a point where this is as push-button as possible. So, we need to continue to push the technology and associated with that will be a further decrease in costs. As the interpretation, in particular, gets more streamlined, we’re going to save the laboratory’s money. They’re going to be able to scale and that will allow it to get into the systems more effectively.

Daniel Levine: Last month, Illumina Genetic Alliance announced the creation of the iHope Genetic Health program. What is iHope and what does it seek to do?

Ryan Taft:

Yeah, I’m super excited about this program. We’ve been essentially piloting iHope at Illumina for almost eight years. We realized very early on that there were going to be lots of patients who would benefit from this technology who weren’t going to be able to get access to it, and so we started a philanthropic program to try and close that gap. It started with just a few genomes being donated by the company. And then over the last few years, it’s grown to 500 plus patients per year. The whole idea was to push into areas of the U.S. and areas of the world where they would have a really hard time getting access to this. And we’ve seen really amazing effects. We just presented at the American Society of Human Genetics on the last thousand or so cases that have come through the program.

We had clinics that we were partnered with in nine countries, a total of about 24 clinics, and we were able to provide definitive diagnoses in about 42 percent of those cases. So, more than 400 children got a diagnosis through the program. What was really exciting to us about that data was that we now had enough cases to start to ask questions about what was happening in WHO categorized high-income versus low- and middle-income countries. And what we saw was that we were actually able to provide more children proportionately with a diagnosis in low- and middle-income countries. It makes sense. Many of them had much lower levels of previous testing. Those patients received more new diagnoses or unexpected diagnoses through genome testing. But what was really fascinating is that when we looked at the clinical utility of the test, like how many of these patients had a change in management as a result of the program, it was almost equivalent between high-income and low- and middle-income countries. So, in both cases of about 62 percent of those kids had a change in management. This really starts to, I think, change the narrative about when and how this kind of information can be impactful. It’s not just going to be restricted to top tier academic medical centers. It can still have an impact even if the child is being seen in a more resource limited setting. So, we’ve been thinking for years about how do we scale this program? It’s not hundreds of patients a year, but tens of thousands or even more, and so that’s what we launched just a few weeks ago. Illumina committed $120 million in kind, so that’s reagents to run the sequencers themselves, software access, , and expertise, and they’ve donated that to Genetic Alliance. And then Genetic Alliance is going to have effectively what amounts to a grant program to enable other laboratories and clinics to do exactly what we’ve been doing. The idea is to democratize the program. So, instead of having all of testing run through one lab at Illumina headquarters, it’s going to run through dozens of laboratories all over the world to get that kind of scale.

Daniel Levine: I, I want to touch on a little more on how the program’s going to work, but, you know, half of this is going into low- and middle-income countries. A third of it is going to countries in Africa. I want to touch on a point you mentioned earlier. In these resource constrained areas, I think a lot of people might say these kids aren’t going to have access to therapies, but you’re actually finding it’s changing the treatment that these children are receiving.

Ryan Taft: That’s right. We still need to generate more data about exactly how that’s playing out, which therapies are available, which ones aren’t, but I’ll come back to that because we have a proposal here to get multiple partners engaged in helping with that. But I can tell you that the data we have in hand right now shows that we are seeing changes in management in low- and middle-income countries. Sometimes those are, as we talked about earlier, just putting them on the right supportive care pathway. So perhaps it’s not an enzyme replacement therapy, but it is appropriate screening for that patient downstream if, for example, part of their condition is a predisposition to cancer. We have seen cases though, for example, a child who was seen in South America in a more resource limited setting where we found a copy number variant associated with a dystonia and that child was responsive to levodopa. So something that was easily available to them and led to a dramatic quality of life change. So, I think the assumption that these children aren’t going to see benefit is one that we very seriously need to look at and whether that’s actually bias in our thinking. I think it is. And I think we can absolutely go with confidence into these regions and deliver precision diagnoses and reasonably expect improvements in their care.

Daniel Levine: This is a $120 million effort. it’s not just a matter of paying for testing, but it’s really establishing infrastructure and training in these countries. Is that correct?

Ryan Taft: Yeah, that’s right. The idea here is that this will form the nexus of a set of partnerships, which will help enable testing in these laboratories and support these clinics. So, you can imagine that there are technology companies that would be interested in this, pharmaceutical companies and other nonprofits. The program, again, will be run, administered, and housed at Genetic Alliance. I don’t want to speak on their behalf, but I can say there’s a lot of exciting developments ahead in terms of the partners that are going to come on board to support this.

Daniel Levine: Yeah. I say that to suggest this should have a much more lasting impact than just doing $120 million worth of testing.

Ryan Taft: Yeah, absolutely. The metaphor one of my colleagues used is: we have a boulder at the top of a hill, we’ve given it a nudge, and now it’s rolling down. And that’s exactly what we’re trying to do here. This isn’t a single shot—let’s sequence a bunch of people or a bunch of kids and see what happens. This is, “How do we lift the entire ecosystem so that it becomes easier to provide precision diagnoses to patients with genetic disease?” Illumina is, of course, a huge piece of that, and the technology is a huge piece of that, but we really are talking about addressing some of those gaps we’ve talked about here in the U.S. In a way we’re kind of sidestepping some of the reimbursement issues in some of these regions. We’re going to increase education. We’re going to work with local governments to make sure we have the policies in place for these patients. And we’re going to build infrastructure. There is a capacity building element.

Daniel Levine: Within the collaboration between Genetic Alliance and Illumina, what’s Illumina’s responsibilities and what are Genetic Alliance’s responsibilities?

Ryan Taft: This is a Genetic Alliance, program so this will operate at an arms-distance from Illumina. Illumina is making the donation, but Genetic Alliance’s leadership, board, employees—they’ll be the ones operating the program.

Daniel Levine: One of the things that I find potentially compelling is that not only are you helping individual patients in all these countries, but there should be an opportunity to really leverage this data. Is that built into this in any way? Is there any way that this will help advance the understanding of rare diseases and genetic variation?

Ryan Taft: Yeah, absolutely. So, there’s going be two components to that. As part of our philanthropic program, we’ve committed to donate variant-level data to ClinVar, so making sure that the community has access to any variance we’ve identified and further building that knowledge. The second piece to this is that we fully anticipate that patients who participate in this or families that participate in this will be able to get access to their own data through a patient driven data platform. Genetic Alliance already has a partnership with LunaDNA, so we certainly expect that to be part of it. But the idea here philosophically is we want to make sure that this data is available but do so in such a way that we’re sensitive to patient sovereignty, but also national sovereignty. We’ve seen a lot of programs historically, I think with the best of intentions, come into some of these regions, do large amount of sequencing, but then that data effectively leaves them [the regions] and they lose control over it. We want to make sure that doesn’t happen here, so the idea is the patients will own the data. It will be available in a data platform. It will be available to the community, but the patients will gain access to that. We hope what we’ll end up creating is the world’s largest patient owned data resource for the community.

Daniel Levine: iHope Genetic Health will begin reviewing applications for clinical home genome sequencing programs in February 2022. How will that process work?

Ryan Taft: I can give a high-level answer to that, but I think Genetic Alliance is better positioned and I certainly don’t want to back them into any corners. I suspect that we’ll start with something that looks like a request for information to make sure that they’re setting up the program in the best way possible, mindful of laboratory and clinical requirements. Then I think this will roll out, as many grant processes do, with Genetic Alliance saying, this is what we can make available in terms the Illumina component of the donation, but also what they get from partners,. and then seeing which laboratories and clinics are able to apply and meet their requirements and then dispersing those grants. Then I think there’ll be metrics and outcomes tracking on the back end of that to make sure that those donations are having the impact in the community. They, they expected

Daniel Levine: Ryan Taft, vice president of scientific research for Illumina. Ryan, thanks as always.

Ryan Taft: My pleasure. Pleasure to be here. Thank you.

This transcript has been edited for clarity and readability.


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