ViiV’s Lotivibart could forever CHANGE HIV Treatment! | Dr. Babafemi Taiwo

Hey everyone, Raifter O'Razi here, and today I am excited to have a conversation with our special guest, Dr. Babafemi Taiwo, to discuss early pipeline development in pharmaceuticals, specifically at ViiV Healthcare. Their ongoing clinical trials, which are aiming to bring once every 6-month two-drug HIV treatment to market, including sharing some of their latest research presented at CROI, which includes a bNAb, or broadly neutralizing antibody, something we've talked about a number of times on this channel. If you're unfamiliar with bNAbs, I'll put up a card here. Be sure to watch Gil Broder's beautifully presented talk on what they are and how they work. But first, a brief introduction. Babafemi Taiwo, MD, joined ViiV's team as Vice President and Head of Early Development at ViiV in September 2024. In his role, Dr. Taiwo oversees early clinical development teams and research strategy, and serves on the leadership of the research and development and global medical team and the research and development team. Dr. Taiwo has more than 28 years of clinical practice and research experience. He previously served as the Gene Stollerman Professor of Medicine, Chief of the Division of Infectious Diseases, and Principal Investigator of the Chicago Clinical Trials Unit of the ACTG, or AIDS Clinical Trials Group, all at the Northwestern University in Illinois. In addition, Dr. Taiwo served on the Executive Committee of the ACTG and was Chair of the Antiretroviral Treatment Strategy, or ARTS, Committee. He has chaired numerous clinical study teams, including ACTG A5353, which contributed to the development of Dovato, and ACTG A5357, which served as an important proof-of-concept study demonstrating the efficacy of cabotegravir in combination with a broadly neutralizing antibody. Dr. Taiwo has also served on the Advisory Council of the NIH Office of AIDS Research and the DHHS Antiretroviral Treatment Guidelines Committee. He was on the PIs of ICARE Nigeria. He is widely published with more than 200 articles and book chapters and served as associate editor of clinical infectious diseases and on the editorial team of the Journal of antimicrobial chemotherapy. Hi, Dr. Taiwo. How are you doing today? >> I'm fine, thank you. How are you? >> Good. Thank you so much for hopping on with me again. Um so I'd like to start with a really broad question um that I ask all my interviewees, which is what is your assessment of the current state of the global HIV AIDS epidemic. However, you want to answer that. >> Well, I'll I'll describe it as a journey that we're we're on. Uh we're very clear about the destination, which is to end HIV. And uh right now this phase of the journey we have uh we can say that we've made a lot of progress. However, we need to do some uh retooling if I might call that to make sure that we don't miss some of the critical targets that we have set for ourselves on this journey. So you can imagine if you're driving on a on a highway and you need to maybe inflate your tires. Uh maybe you know, uh add some little gasoline to the to the car to make sure that we we have the car working tip-top shape. What do I mean by that? Uh I mean that we have right now mixed a mixed bag uh that includes things that we've done quite well in. We've uh there's now about 32 million people are on treatment, which is great. But we know that there are also areas where improvement is needed. For example, in 2024 there were 1.3 million new infections, which is way higher than we would like to see. We know that stigma still exists. We know that there have been destructions in the in the global funding system that has made uh some of the uh access issues more more challenging. Uh we know there are still kids who are getting who are born with uh with HIV. So, there are many things that we can we can improve upon on this journey. And so much work to be done. >> Yeah, and in our in our last chat, you also talked about social determinants of health. And you know, it's surprising to hear someone who works on uh early pipeline talk about something social determinants It's not something that we often hear talked about together. So, I'm I'm curious to to know what Well, first of all, for those that aren't familiar, can you briefly describe what social determinants of health are? And then, how do you incorporate those factors in your early stage pipeline development? Well, social social determinants of health uh those things that are really not medical by themselves, but they in a very profound way affect health outcomes and also affect equity access to health. And those things are really things that happen to us on a day-to-day basis, where we live, where we go to school, where we buy our foods, the kinds of access we have to transportation. All of those things are sort of immediate normal human needs that can affect health outcomes. But, in the bigger picture, you're talking about you're looking at things such as public policy, political climate, social norms. All of these things in very tangible ways can affect how health is lived beyond the impact of genetics, beyond the impact of medication. Uh these things really can impact treatment and and overall outcomes. >> Yeah, and we've been seeing that a lot, especially in the last year with so many changes to the political climate and social norms and public policy, all those things you mentioned. So, in considering those factors, how do they influence the kinds of decision-making or the direction that you decide to go in early-stage pipeline development? >> I think one of the things that we do is engage the community to make sure that we really have community input at the very as early as possible into the development process. And this is important because our goal is to make medications, so to deliver medicines that really work for the person as opposed to the person trying to fit themselves into the medicine. And we do that in a variety of ways such as thinking about how we can make the medicines last longer when they're administered. So, instead of going to a healthcare facility to get medication every other month as it is available today, can we make that burden Can we lighten that that requirement by making it you know twice a year? By making it three times a year? That would have an immediate impact and instead of mediating or moderating those sorts of issues, and how can we do things that would address social factors such as stigma? How can we think about using medication to How can we remove the the maybe the impact of stigma in that person's perception that they need to take medication on a daily basis? That make it more easy for them to uh forget about living with with HIV. So, these are some of the things that we try to incorporate as early as possible and it leads us in a direction which is really one that we're sort of quite focused on and then making significant progress on the creation or delivery of medicines that uh continue to be excellent in terms of how effective they are, excellent in terms of how safe they are, but also meeting the needs of persons in terms of reducing the stigma, remind us about living with HIV, and having long-acting duration of activity. >> And you were instrumental in the in the development of Dovato, is that correct? >> Yes, I was. >> I think that's a good example, too, of from even at that point from a three-drug regimen to a two-drug regimen for a lot of people was really exciting because it suggested perhaps less toxicity, less side effects, as well. >> Right, I think one of the major contributions, or major changes, developments, advances, you can choose whatever word you want, that we've seen in the field over the last, I'll say, decade or more, has really been the adoption of two-drug therapies as mainstream in HIV therapeutics. If you look back to, say, 15 years ago, the whole idea that you could treat somebody with two medications was something that we whispered initially because the the field had really come to this point where three drugs were considered to be absolutely critical. And the field didn't get to that that common sort of agreement by chance. It was because we had tried single medications called monotherapy, didn't work. We tried two drugs called dual therapy, it didn't work. And so, we found that three drugs worked. And so, the world had gotten to this really comfortable area where three drugs appeared to be what you had to do. And it seemed like we were dialing back the clock when we said, "Actually, look here, we can treat with two medications." But guess what? The reason that whole idea was possible is because of the power, the effectiveness, and the safety of a drug called dolutegravir. That drug really changed the face of HIV treatment, and remains to date the most potent medication, certainly by the way I and many others look at it, the most potent HIV medication that's in current clinical use. And that really allowed us to do what we could not do before, which is to try to create two-drug regimens, which is why the early generations of two-drug regimens that the field embraced were actually dolutegravir-based. That was the drug that's at the core. And you fast forward till today, when you look at the pipeline of drugs that are in development across our fields, you will struggle to find any regimen that has three. Perhaps I can think of one regimen in development that has three, but in essence, but all the other drugs essentially have two medicines. What a change we've seen over the last decade. >> And I guess that begs the question, too, do you see the potential in the future for a single-drug regimen? >> When you say single-drug regimen, I assume you mean one medicine as opposed to one medicine that has two, one pill that has two drugs in it, or maybe um co-formulated medication. But if if we're talking about just having a single medicine instead of the two that we have now, that is a bar that is actually uh considered very, very high. And right now, I think we're all we've sort of gotten um comfortable with the with using two really good medicines. The idea of using just a single medicine is one that uh it's it's it's way it's it's a little outside of what we have been able to to achieve. We never say never. But the challenge in front of us is significant. And it is because the virus really is very smart. In that it can mutate, it can change in ways that make it difficult for make it eventually to overcome many of the drugs that that that one could could envision. But there are certain things that are still that have been talked about to make this whole um simplify treatment and make it essentially seem like you're taking one medicine. Co-formulation things, for example, would be uh done that with a pill and maybe we can even think about it in other ways. >> And okay, so how do we ensure that or how do you ensure that community has a seat at the table during early stage pipeline strategy? >> One of the things that we do is to have advisory boards. And those advisory boards occur early and they occur multiple times during development process. This is where we essentially lay bare the the the thoughts that we have and get ins- input into our thinking, where we need to make changes, and that really has become part of our I call it standard operational operating rules. And they, of course, are extremely important in shaping the final design of our clinical trials, the final design of our uh approach to even how we roll out product, etc. All of these have significant input. And why do we do that? We do it because we believe that everything we do must have the person at the center of it. And so, we can imagine that it's hard to to develop something for a person without the person's input. And so, that is really part of our culture that we hold very dear. >> And earlier you mentioned um health equity. How do you prevent new innovations from widening the health equity gap that already exists? Um things that including um like funding or supply chain consideration, access. >> There is um there's a commitment that um we've shown that ViiV has shown as a company over the the years, which is to really um make medicines that address the needs of persons, but also to uh be very thoughtful about how these medicines are made available to persons who need it. And there are are examples of really outstanding success that that has been demonstrated. If you look, for example, at how our pediatric uh medications have been made available for a pediatric populations, but even the drug that I alluded to earlier on, dolutegravir, you'll know that you should know that dolutegravir is currently being used by about 25 million people uh globally. And that is really uh because of very creative uh collaborative collaborative work that ViiV did with governmental agencies, with um uh the medicine uh patent uh group, and and other stakeholders, community members to make sure that these medicines are available. Uh similar things have been done uh for cabotegravir. And so, this ongoing um commitment culture of of doing things to make sure that medicines reach uh persons who need them, regardless of where they're located, is something that uh as exemplified and and actually led him and continue to do. >> Okay, so with over half the population in some areas of the world um being people living with HIV over the age of 50, should we also be pivoting or expanding uh the pipeline to treat specifically HIV-associated chronic inflammation and the comorbidities that can go along with that? >> That's an interesting question, Raif. I mean I mean the most effective way to prevent these comorbidities that we're talking about is to keep HIV fully suppressed. And that is number one goal. And the medications that are medicines that are available now actually do that quite well. The other thing that is important is to make sure that those medicines don't by themselves contribute to these chronic conditions. And when you think about these chronic conditions, the heart comes looms large. Liver complications loom large. Um kidney issues another consideration. Neurocognitive brain-related issues. So all of these things are potential effects of HIV by itself or um some of the medications that we used to use before. So it is important that as we progress, which is one of the things that we're really proud of, is that the medicines that we're bringing uh forward are intentionally as opposed to not only suppress the virus, but also to be uh to have excellent long-term uh safety. Because as persons get older, they naturally will have more and higher risk of having some of these comorbidities. And the last thing you want is a medication that would complicate that. And that speaks to why one of the reasons that really informed the move towards two drug therapy. And we're beginning to learn more and more now that actually giving somebody three medicines when two can do the job is not not a good idea because the third medication we're learning can actually do things and have a some some effects long term like maybe on the liver, maybe on metabolic health and things like that. So the history that we have right talking about the two drug paradigm talking about focus on medicines that are safe and have long term evidences support that. Really would help in the long run to reduce some of these things that we're worried about in older person as person get older. >> Mhm. Okay. So speaking of new research, um can we talk a little bit about the latest findings that you that was shared at CROI this year for the embrace study? It's the medication known as N6LS. >> Yes. The medication is also known as Latuvibart. So it's now gotten a that new name Latuvibart. >> Okay. >> It is in a class of medicines called broadly neutralizing antibodies. What that means is that these are proteins that the body makes that can fight HIV and so kill HIV. And they made into medicine. Not only can it fight HIV, there's the expectation that perhaps it has an effect on the immune system to boost the immune system in ways that might benefit the person. So, this drug actually, we think might have a work in two ways. One is to just simply fight HIV, kill it, but also to help the immune system, which makes it a very special uh medicine. And thinking about uh drugs in this category uh is the one that perhaps the one that has is one of the ones that has the best in terms of how well it can work. And EMBRACE study essentially took this new uh medication, lutetium bars, called N6 cells. And combined it with a tested, well-known medication called cabotegravir. And that was the regimen that was tested. And the whole idea is, can we give this medication as a long-acting regimen? And when combined together, what it showed essentially >> [snorts] >> was that it was effective in keeping the virus suppressed. Which means that it worked well as an antiviral. And participants were followed up to 12 months. And the 12-month data is what was reported at CROI, showing that in these persons who were given the medications intravenously, it really worked uh very well. And some patient some participants also got the medications through the subcutaneous route. But we've actually sort of made the decision after looking at all the data and all the evidence that we will be we are uh moving uh forward with the intravenous >> Okay. >> of this medication. And and uh the next step >> that means using an IV for those wondering. >> using an IV, right, in combination with with a a second drug. And right now we're we started actually we started enrolling. We are fully enrolled now. We fully enrolled into what is called EMBRACE part two. Very exciting because in EMBRACE part two, both the drug I mean this drug this drug is being given every 6 months. Lutetium bar is being given every 6 months. Why is that important? It's important because we're looking for treatment that can be given every 6 months. And Lotivir Lotivir part in combination with an integrase inhibitor is showing significant promise as a combination that might get us to that uh Q6 months treatment regimen. And so we're moving closer to it. We're super excited about it. And look forward to sharing more data about it in upcoming uh conferences. >> So in this EMBRACE part two, the the Lotivir part is going to be once every 6 months and the cabotegravir is that once every 4 months? >> Uh in this study, it's given every 2 months. The cabotegravir >> Every 2 months. Okay. Got you. >> The Lotivir part is given every 6 months. Now mind you, when we're done with our full regimen, we're going to our goal is to come up with a regimen that both drugs are given every 6 months. But this is the journey that we're working toward. This is not, right? This is still the phase two study. We're still building the case. By the time we get to phase three, by the time we get it into the clinic, what we hope to deliver is a regimen that both medicines will be given every 6 months. >> Okay. So folks, this is kind of like the progression of clinical trials and you have to start with these uh smaller durations to make sure it's safe and effective um for the new new drugs and the the the uh already approved drug. And then so we're working up towards the 6 months here. So that's that's exciting though. >> Super exciting. Super exciting. >> Babafemi, you've spent decades looking at HIV through a microscope, but also on a clinical chart. When you sit across from a newly diagnosed patient today, what is the single most hopeful thing that you can tell them that you maybe necessarily couldn't tell them 10 years ago? >> Uh I hold their hand and I look in their eyes and tell them that despite this new diagnosis, they can still expect and plan to live the full life that they had envisioned for themselves before this diagnosis was known to them. And that's because they can expect to have the life expectancy that they'd planned before. They can expect to have the relationships that they'd planned to have before. They can expect to have whatever sort of um life they had. If they were uh desirous of having children, they can still expect to have that. In other words, this should not significantly bend the trajectory of their lives. And that they can go on and still have an amazing life despite the diagnosis. >> And in kind of looking at your role as a doctor, I'm curious to know how you originally got into work related to HIV. >> Well, I trained uh in Nigeria. I went to medical school in Nigeria, and when I came to the United States, I wanted to uh specialize in something that would have global significance. Meaning that I would be able to not just work and have an impact in the United States, but be able to impact uh the rest of the world and specifically sub-Saharan Africa and more specifically Nigeria. And looking at the sort of available uh options and where the need was greatest at that time. It was really HIV. People were dying from HIV. We hadn't gotten to this where we are now where HIV is now uh can be treated is a treatable disease the treatable condition. It was then really um a life sentence that that was a death sentence in many cases. And so it seemed like something that that really could uh engage my my interest. I could put my time there and and hopefully make a an impact on the global scale. >> And when you are not researching groundbreaking innovative potential new treatments, prevention, what do you do when you are clocking out at the end of the day and going home? How do you unwind? How do you ground yourself again? >> Well, uh I like to to run. Uh I do that uh religiously and I get very angry when I'm not able to do that. >> [laughter] >> So I'm I'm an obligated runner. I like to read things that are not medically inclined at all. Uh so I I read I read very widely across a a range a range of things. And I like to spend time with uh with my family. And and uh also watch watch movies and things like that. >> Excellent. Well, thank you so much for sitting down with us today um and giving us a little more insight into your work. Is there anything else you'd like to share uh that we haven't been able to address yet? >> I I think um we are at an amazing uh moment here where new treatments are really coming up. And when I think about the next 15 years in HIV landscape of the HIV landscape, I think it'll be quite different from where we are today. I think there will be a significant presence of long-acting treatment than ever before, perhaps more than half of people may be on some kind of long-acting therapy. Uh many of them will be injectable, some will be taken by mouth, which is fundamentally different from where we are today. And that means that we'll have more choices, more more options that will be able to be customized to the person uh to each person uh to make sure that we at the end of the day uh end HIV. So, the very hopeful future on the journey that I initially described that to you. >> Well, thank you again so much. It's been a great conversation, and I hope to to bring you back on for some more, you know, in-depth conversations about specific topics as well. >> Thanks for the opportunity. >> Folks at home, please um comment below your thoughts, comments, and questions. I'm happy to follow up. Don't forget to like, subscribe, hit that bell so you get a notification every time a new video comes out, and please share this with anyone who might find value in this type of content. Those are the best ways that you can help support me and my channel. All right, until next time. Cheers.