Prakash Bhuyan, MD, PhD, vice president of clinical development at Inovio, discusses the company's vaccine trial for coronavirus disease 2019 (COVID-19) as well as its DNA medicine platform for rare genital cancers.
"One of the things that I think I and our investigators, and quite honestly our patients have remained focused on is trying to not lose sight that cancer is still a monster. We must not lose our focus on other things that actually cause tremendous medical and psychological physical impacts on on patients," said Prakash Bhuyan, MD, PhD, vice president of clinical development, Inovio.
AJMC®: I'm Mary Caffrey with The American Journal of Managed Care®. And we're here today with Dr. Prakash Bhuyan, the vice president of clinical development at Inovio. In the time of COVID-19, public health leaders tell us that the long-term solution is delivering an effective vaccine against the virus. And Inovio's Dr. Bhuyan is here to tell us about the company's efforts against COVID-19, as well as science, to prevent rare, but deadly genital cancers. Welcome, Dr. Bhuyan.
Dr Bhuyan: Thank you, Mary. I appreciate the time today. We certainly have been really immersed in these activities against COVID-19. But really, I'd like to take this time to talk to you about cancer and our efforts to move our phase 3 and phase 2 programs for VGX-3100, which is our lead candidate of DNA medicine approach into, eventually, the bedside.
One thing that I think, as we're in our very unusual usual circumstances that we're all trying to do, broadcasting from our home offices and working from our sequestered homes—one of the things that I think I and our investigators and quite honestly our patients have remained focused on is trying to not lose sight that cancer is still a monster, and that if we don't continue our efforts towards trying to come up with treatment solutions for that, that would be more than a miss—that must not happen. We must not lose our focus on other things that actually cause tremendous medical and psychological, physical impacts on patients. So, for VGX-3100 we've really tried to keep that momentum going. It's been very challenging. …
It's really the patient need that's allowed us to keep our focus. And so, we have these these 2 trials that we've just disclosed results, preliminary results on which are our phase 2 trials for vulvar dysplasia and for anal high-grade dysplasia. And so, you know, we can certainly, I can tell you more about some of that, but we're pretty excited about some of our preliminary findings.
AJMC®: We certainly want to talk about both the COVID-19 vaccine efforts and both of those trials. I absolutely want to talk about both of those things. Let's talk first about your efforts with Inovio and Ology Bioservices just received an $11.9 million grant to deliver vaccines with the military. Can you tell us a little bit about that?
Dr Bhuyan: Well, I think we're trying in all efforts of our company to get funding for our DNA medicine platforms, so we're really looking where we can to be able to empower our research programs—so that is going to be pivotal in terms of helping us to develop our platform. Our platform is a DNA medicine platform. So, we're using that to try to really direct the immune system. I mean, as an immunologist myself and as an infectious disease specialist, we have learned so much about immunology over the last many decades and at this time, I mean, this particular time, is probably an example of this.
I think we all know [when it comes to] infectious diseases, a lot more than we ever wanted to. We know that a single virus can paralyze our global community and [that] can really be a very frightening thing. Now, this is something as an infectious disease specialist that I've trained and had to be cognizant of my entire career life. But what's exciting is that now, we have an opportunity and ability to use our tools that Inovio and other companies are obviously pitching in and trying as well. We have to be able to use what we know about the immune system and about infectious diseases to be smarter about this and to come up with modern tools to be able to develop therapeutics. I want to go back to the fact that you know, we talked about coronavirus and it sort of permeates our entire life right now.
However, we should remember that human papilloma virus [HPV] is the number one cause of cancers caused by virus. It's the number one oncovirus in the world and we have, as yet, not been able to put a dent in terms of the remaining cases of cervical cancer, anal cancer, and vulvar cancer, so it affects men's and women's health still quite a lot in this 21st century. We need to do something about that. So, I mean, again, that's why every day when I, myself, my team, we wake up in our homes now and we work. We're focused on trying to move these programs forward.
AJMC®: So your approach at Inovio is to develop what you call DNA medicines to trigger that immune response. Can you talk about this global approach that you have that go against many different conditions?
Dr Bhuyan: Well, the nice thing about this platform is DNA is very, it's very facile. It's very easy to make, very easy to characterize—and which is why we were able to get into clinical trials very rapidly. And that's the kind of solutions we need, because our current problems they emerge immediately. I mean, in December we would have been having a very different conversation than today as we sit in April. And I think we were excited about our platform because of the speed at which we can we can develop things and be able to get into research trial. So right now, for example, with what we've seen in our phase 2 trials for VIN and for AIN [anal intraepithelial neoplasia], which are vulvar dysplasia, vulvar precancer and anal precancer, we've seen a proof of concept, an initial proof of concept. These are preliminary data. So, we still have to see and we will be reporting on complete trial data as we go through the year. From that our plans are to try to approach regulatory discussions and frame out what a full development program would look like going into phase 3.
AJMC®: So, your lead candidate that you mentioned VGX-3100. You're in phase 3 trials for cervical dysplasia, and you just recently released those interim phase 2 results for precancerous conditions related to vulvar cancer. What are the highlights of those interim phase 2 results that are just released?
Dr Bhuyan: Well, for vulvar cancer, what we saw, so we reported on 50% of the data available, so we still have the rest of the trial to do but on those data, what we've seen is that 80% of women had an average of a 60% reduction in their lesion area. So, this is a disease, just for context, that typically doesn't change for a period of years and typically only 2% will spontaneously regress, as in the lesion will go away without any treatment. The current treatments are surgery, which are disfiguring, painful, and psychologically devastating. And 50% of the time the lesion just comes back again. So, these patients, these women are really focused and wanting a better solution. And we really owe it to them—we need to develop better solutions for them, because the current solution of using a scalpel to cut out a viral particle makes no sense at all. And unfortunately, we've been doing that for decades. It's time that we use a more intelligent approach and an immunologic approach against the virus, namely HPV. So, the fact that 80% had this effect of a decrease in legions is very promising, because that happened 6 months after the last treatment dose and typically, you would only see on a disappear disease in 2%, for example, of women, and that wouldn't happen for years. So, I think I think this is reassuring, it's telling us we're in the right direction.
AJMC®: Are there similar results for VGX-3100 that look promising to prevent anal cancer?
Dr Bhuyan: So, for anal cancer, you know, again, a very unique disease, a unique population of men and women. In fact, if you had to look at the proportion in the United States who get anal cancer, there are more women today who get anal cancer than men—60% to about 40%. And by the way, for these conditions more than 1000 [people] will die of cancer from vulvar and anal cancer just this year, that's the estimated number and that hasn't changed for decades. But in this phase 2 study for AIN, which is about the same size in terms of trial data, we saw half of the population respond where the HPV 16/18 positive precancer disease actually went away. And that is that is really in line with what we've seen with our cervical trial data, which is now in phase 3. And I think again, it's very encouraging and it's the kind of thing that makes us it's what gets us up in the morning, you know, no matter where we have to do our work. Again as context, I think it's important to understand for these patients, it's surgery that they that they get, and they get that almost every 6 to 18 months for their precancerous lesions and half of the time the disease comes back and so they're getting repeated surgeries in the in the entry and oh canal which is painful site again, so psychologically devastating. And honestly, it's all we have, but we need to do better. And that's why we're doing this.
AJMC®: So, in managed care we hear so much about the importance of quality measures, and there's more and more emphasis on patient-reported outcomes. So, it sounds like there's a lot of potential through this vaccine to improve those measures and improve quality of life for patients.
Dr Bhuyan: Absolutely. I mean, we actually have patient-reported outcomes [PROs] tools that are that we're using for that we have in both of these trials. And we're actually collecting that information, both at the start of the trial all the way through the trial. And we're actually seeking to develop a new tool. There actually, is not. If you can imagine there is not a PRO tool, this specific for vulvar disease in particular, so we're actually seeking to actually modify some existing tools and try different—something that would be fit for this disease, but it again shows you that patient reported outcomes are an evident need to be able to understand, measure and improve. We don't even have appropriate tools involve our dysplasia, which shows you how neglected that field really is. And that's again, that's another thing that just has to change.
AJMC®: So, even though these cancers are still relatively rare, they are becoming more common. With a vaccine like this, what's the potential to slow the trajectory and reduce healthcare costs along with improving quality of life?
Dr Bhuyan: So, I think that's a great question. And, you know, what, what we're using again, is a DNA medicine. This DNA medicine approach to stimulate the immune system on its to also create a hopefully a systemic effect and not just a localized effect. So in other words, HPV is multizonal, it affects more than just the cervix, it affects often more than just the anal canal or the vulva-vaginal area and head-and-neck area for example, those are the primary areas, a lot of patients have diseases they don't even know about. And sometimes when they present, they present with outright cancer. So, the earlier we can detect these things and treat them which would be using for example, VGX-3100 would fit into that model that way, early detection and early treatment would allow us to then prevent some of these repeat surgeries these instances where women and men are presenting with outright cancer which is a much more difficult and costly burden on the on the healthcare system.
AJMC®: So, what are the next milestones we should be looking for with VGX-3100?
Dr Bhuyan: So, the next milestones will be the complete set of data for both of our phase 2 trials. So, we have the vulvar precancer trial, the anal precancer trial on, and then milestones from that will be regulatory discussions to frame out on the following development program towards licensure. And then, you know, obviously contingent on positive data. And then on, what we would also be looking at is our cervical program, which is, as I said, in phase 3, so those are the sort of key pieces of data for this particular product.
AJMC®: We came into this discussion talking about Inovio’s work in COVID-19. And I understand that your vaccine was tested in the very first volunteer—the first volunteer received the vaccine this week, is that correct?
Dr Bhuyan: Yes, that's right. Yeah. We're really excited about that. And I think I think we all need to be pulling in this direction to get us out of the pandemic.
AJMC®: So, when would we be looking for some news about the results of the vaccine?
Dr Bhuyan: Vaccine? Well, this is the phase 1 trial, so on towards the end of the year, there would be targeted results from this and then that would allow us to also get into our phase 2 piece of development. And I think it's really at the end of the year that we're aiming for, but obviously, we're aiming as fast as we can... we're going to be relentless in terms of how we're doing this because we need to get out of this situation.
AJMC®: Well, there’s so much going on with Inovio. Thank you so much. Dr. Bhuyan—thank you for talking with us.
Dr Bhuyan: Well, I appreciate it. Mary, you have a great day.
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