Merck's NEWest Drug: Idvynso, also a Once Weekly Drug & Once Monthly PrEP!

[00:00:00]Today I have the pleasure of sitting down with Louisa Stam to discuss the brand new FDA approved drug for treating HIV known as AdvZo. It is a once daily oral tablet that provides another option that may offer benefits to those of you who have concerns or are struggling with your current medication. As always, consult a healthcare professional to address your specific health and needs.

[00:00:22]I'm Ra Dazzi. Thank you for tuning in.

[00:00:24]First, a brief introduction to our special guest. Louisa Stam is a physician scientist at Merc. She works in HIV clinical research where she leads product development across Merc's HIV pipeline. She is passionate about advancing science that can help improve the lives of people living with HIV. As a disclaimer, I am hosting this interview with a representative of Merc because I think this is information that will be useful for you all. I have not been compensated by Merc, nor have I been provided any payment in kind for doing this. I will always let you know if I have been compensated to promote any specific drug or product. And with that said, Louisa, it's so nice to see you. Welcome.

[00:01:01]>> Thank you so much for having me on today. It's been an exciting week.

[00:01:04]>> Yeah, it was great to sit down with you and and a couple others at Croy this year and kind of get to know each other.

[00:01:10]And I'm glad that we could follow up and actually get this conversation going.

[00:01:13]>> Yeah, it's great to see you again.

[00:01:15]>> So, if Louisa, if you could just break down for me what Adenzo is. Yeah, thanks so much again Rafe. And so last week Adenzo was approved in the US by the FDA for the first time and it is a non-instinct nafavir free two drug complete regimen for the treatment of HIV in people whose virus is viologically suppressed and it's the combination of davverine that has an established safety and efficacy with islativir a new medicine that has multiple me mechanisms of action including transllocation inhibition.

[00:01:50]>> Okay. So when you mention noninsty insty is a cla we're talking about classes of drugs and each class kind of tackles HIV in a different way.

[00:02:02]>> Yeah that's right Rafe. So complete regimens for the treatment of HIV put together different medicines and different mechanisms of action that work together to really strongly inhibit the replication of HIV and control the virus. And in recent history, it used to be three drugs was common and now we're down to two. So does that is that are we decreasing toxicity potential? Is that are are the two drugs just able to do more than what they used to be able to do where we used to have to have three?

[00:02:36]Yeah, it's really representative of the evolution of the treatment of HIV and how over time we've developed better um and with by better I mean stronger and um more potent medicines that have improved safety profiles and over time it looks like we're moving to fewer medicines.

[00:03:00]Currently, two drug regimens such as AdvZo have demonstrated favorable safety and efficacy that's comparable or non-inferior in the scientific speak of our clinical trials to the standard of care medicines that may contain um two or three medicines and importantly in a head-to-head blinded study against Pikarvey which is an instybased three drug regimen and a really common standard of care. So when you say head-to-head blind study, you have participants that are taking Victarvey and then you also have participants that are taking advo as the scientist don't know which participate which participants are taking what. That's the blind part.

[00:03:45]You're just looking at the data and then in the end it you reveal who's taking what and then are able to compare the data.

[00:03:53]>> Yeah, that's right. And it's blinded not only us as the sponsor running the trial, but the people in the trial don't know what they're taking, nor do their doctors or nurses or staff at the sites know what they're taking. So, a lot of people will call this a double blind study. So, no one knows until the very end. And the people taking the medication um are taking both an active and a placebo at any given time. So, and they don't know which one is which. So at the primary end point it's revealed to the sponsor um and then you can look in a very unbiased way because no one knows anything before then um about how the drugs are compared.

[00:04:34]>> And for those people who aren't familiar with clinical trials, can you uh define what an end point is?

[00:04:42]>> Yes. So an end point is um an objective or an assessment. And so for HIV trials, depending on the population, you're looking at the levels of HIV virus that are circulating in the blood at a given end point. So for a verologically suppressed population in a clinical trial, you're looking for maintenance of HIV um less than 50 copies per mill. And the end point from an a regulatory perspective because this is what the FDA and other regulators are looking at in this population is the number of people who actually don't suppress the number of people who have HIV greater than or equal to 50. So that's when we have our first look and it's the most important look. So it's at after a year or 48 weeks of treatment. The trial continues beyond that. So we can continue to establish that those results that we see after one year are durable after two years and beyond that potentially in an open label extension. So the study will go on beyond that but that is the critical most important look and that's what supports the initial approval of a drug like Invo.

[00:05:54]>> Gotcha. Thank you. I'm using you um not only to tell us about Invo but also to help get people caught up on on clinical trials and the science as well. I think it's really fascinating.

[00:06:06]>> I'm here for it. Race, anything.

[00:06:08]>> So, I guess the the first question that comes to my mind is why another daily oral pill? We have, you know, a few on the market now. Why why another one?

[00:06:18]>> Yeah. So, the health needs of people living with HIV are changing over time.

[00:06:22]And as people age, people living with HIV are now managing chronic medical conditions and multiple medications. And so Venzo is a new option for the treatment of HIV that can address some of these needs. And it stands apart in a couple of ways, some of which I just mentioned. It's a combination of two drugs. And importantly, it doesn't contain an insty or a tonafir. And inst are the current currently um used standards of care.

[00:06:50]>> And I believe um like some of the concerns are with weight gain. I get a lot of followers asking me about weight gain. What how what is how is Adenzo as far as weight gain?

[00:07:01]>> Yeah, so we've conducted two large phase three clinical trials um head-to-head with standards of care generally in an all cumber study and then against Vic Tarvey um in a head-to-head blinded study and compared to those other regimens derain or advinco um is neutral with regard to weight gain. In one of these studies, we did see that there was weight gain, but it was more about the drugs that they were coming off of. So, some ARVs suppress weight gain such as a favor and tonafir containing medications. And so, for people who are switching from those meds, they tended to increase on derin latche. But overall, the profile with regard to weight is very um comparable to other standards of care for HIV. And as you said um you know people's health are changing and their HIV medications may need to change as well and so this could be for weight gain as you mentioned there are other reasons uh and advo expands the therapeutic diversity to provide additional options to people >> and you mentioned that it's tenafare free specifically and that includes TDF and TAFF. Um what are what were some of the concerns around Tanafav specifically? Yeah, historically tanafir containing um toxicities tend to um fall into two categories, bone and renal. Um both of which are really important to people living with HIV as they age.

[00:08:32]>> So bone density and then renal has to do with the liver.

[00:08:35]>> No, it it has to do with the kidney. Um and >> kidney. Okay. Um can someone who is newly diagnosed take advo? So I mentioned the two studies that we presented at Croy in 2025 in the virologically suppressed population and this year at Corey 2026 we presented another year of data on the verologically suppressed plus another phase three study in treatment naive individuals and there again um Invido had comparable efficacy and safety profile compared to big tarvy in people who had not been treated with HIV yet.

[00:09:14]So, this isn't in the current approved label for Adenzo, but we're working on submitting a label expansion to include people who haven't been treated with HIV so that they may be treated for Inzo in the future.

[00:09:26]>> Okay. So, the FDA approval for now is for people who are already on some type of medication, are virally suppressed, undetectable, they can switch to Denzo.

[00:09:36]But if you're newly diagnosed or like you said, treatment naive, which means that you've never had treatment before, it's it's a first for you, then it's not we're not quite there yet.

[00:09:46]>> That's right. Stay tuned. Yeah, but the clinical data are supportive and and and positive. So, um so we're waiting on that and then the regulatory review will happen. So, probably next sometime next year, right?

[00:09:56]>> Great. Okay, that's cool. So, sometime 2027 is what we're looking for. That gives some a little timeline for people.

[00:10:02]Great. When will this drug be available uh for prescription?

[00:10:05]>> Yeah, so in the US it'll be available by miday.

[00:10:09]>> Midmay. Okay, that's coming up in a few weeks here.

[00:10:12]>> Right around the corner >> real quick. And what will the availability be like outside of the US maybe considering the EU? Um Africa LMIC's low meaning low and middle inome countries.

[00:10:24]>> Yeah. So it is already approved and available in Japan and we're currently working on the submissions and approvals. uh outside of the US and Japan. So including including Europe and many countries rest of world regarding low and minimum middle inome countries.

[00:10:42]Uh Merc has a long commitment to increasing access uh across the world and we've been historically working with local governments and funders and even generic manufacturers to increase access globally for HIV medications.

[00:10:57]>> Okay. So there you are planning on having some sort of affordable generic version of this drug.

[00:11:02]>> Yeah, over time as we have done before.

[00:11:05]>> Okay. Uh I do have a couple questions and comments from followers. Um I just posited in my story last night if if people wanted to submit things. One was how far are we from taking one or two tablets a year?

[00:11:21]>> That is a great question. Um and we've come a long way and HIV treatments continue to improve. Uh right now new new innovations are all focused on long acting options and I think taking a tablet once or twice a year is an aspirational scientific goal. Um along the way we can expect some incremental progress with longer acting oral injectables. So it's that would be that would be awesome. Reefe um we'll get there over time and we'll make some progress on the way. And one person just had a comment slightly unrelated to HIV specifically, but said, "Just want to say thank you for the heepsi drug, Zepper, if I'm pronouncing that correctly. I was diagnosed and treated quickly."

[00:12:00]>> Yeah, that's really nice. So, thanks for sharing that on behalf of Merc. Um, I really appreciate that. And I'll just add that at Merc, we have a long-standing commitment to infectious disease, uh, outside of HIV and including in HIV. And it's really nice for us to hear about how we're positively impacting people's health.

[00:12:16]So, thanks for sharing that. And then the final question was is it gonna work with a person living with CKD or chronic kidney disease?

[00:12:24]>> Another good question. So this depends on the degree of kidney disease. So Adenzo can be used in the setting of mild or moderate disease without any change um to uh how you would take it.

[00:12:35]Uh but it is not approved for use in people with the most severe kidney disease or on dialysis.

[00:12:41]>> Thank you for that clarification. Um so I have a personal question. Um, so I had once taken a tripleta back in the day, I think around 2012. Um, it was like one of the first single tablet regimens, a three drug, and I believe a favor was one of them. It's and that's an NNRTI. I had crazy uh like vivid dreams. I mild hallucinations, crazy like um psychiatric effects. So I'm curious how something like Draarine which is also NN an RTI compares.

[00:13:17]>> Yeah, a triplo when it came along was amazing because it was the first single tablet regimen Rafe and um it really was a gamecher for the field of HIV. What you experienced unfortunately was not unique and many people reported having what we call CNS effects uh like the hallucinations that you had mentioned.

[00:13:39]So that was common to what we call first generation NNRTIS like a favor. So when during was developed which is also an NNRTI it was um we had those kind of that AE profile those side effects in mind when we developed derine and we really worked to um demonstrate there is an improvement with the second generation NNRTIS. So in the original Davverine studies, drive forward and drive ahead, we looked very carefully at the side effects like you mentioned the CNS side effects and we were able to demonstrate that with the second generation we addressed a lot of those side effects that were seen with a uh with NNRTI like a fabins.

[00:14:22]>> Okay. I'm really glad that you were able to clarify that because I'm sure some people when they hear NNRTI that's like the first thing that they'll think of.

[00:14:28]So that's great that we um made progress in that way. Yeah, certainly with the with regard to the safety profile and then it also in in terms of the resistance profile during covers a lot of the mutations that a favor didn't cover. So we made a lot of progress from the first to second generation in NFTI.

[00:14:45]>> Can we talk a little bit more about resistance? Uh what how um does Advo hold up as far as staving off resistance versus other um drugs that we've mentioned like Victoria and Dovato?

[00:14:59]>> Yeah. So let's focus in on the clinical trial data that we shared from trials 51 and 52. Um and in those trials we compared it to both um Victarvey and to other um standards of care for HIV treatment with regard to resistance.

[00:15:19]Invo is uh overall um has demonstrated some good results. And in the phase two studies which enrolled about over 700 people um who were who took advo, there were 10 people who had HIV viral loads that were equal to or greater than 50 copies per mill before or at week 48, which was the primary endpoint, about a year into treatment. And of those 10, there were four people who had resistance that was detected pre-treatment prior to switching to advanc. And of those, only one person had at the time of the vymia knew resistance. So overall favorable.

[00:16:06]>> So there was one person who developed resistance while taking the medication.

[00:16:12]Is that correct?

[00:16:13]>> Yes. Of the over about 700 people who took it. Okay, that's that's great. And is there overlap for people who have like I guess my question is for people who have developed resistances. Does this provide an option that will give some coverage to people who have developed resistance to other drugs?

[00:16:32]Like is this another like backup I guess?

[00:16:35]>> Yeah, great question. So we studied it in people who were viologically suppressed and then were switching to another regimen. We did not include in the clinical trials people who failed prior treatment regimens and actually if you look at the indication statement it's for use in people who had no history of treatment failure and also >> gotcha >> invo is not indicated to be used in people who have a history of resistance to davverine which is one of the two components of infinso.

[00:17:02]>> That makes sense. Okay. Is that something that you might explore down the line? Yeah, I think as we continue to innovate, we'll look for um combinations of drugs that will have better resistance and more potent um activity to virus.

[00:17:21]>> Well, okay. Speaking of future research, can you talk a little bit? I saw that there's some upcoming research or I'm not sure if it's ongoing now with a slat in combination with lenapir.

[00:17:36]>> Yeah. So we've been talking a lot about uh islatravir as a new drug that being used in a daily combination with davarine. But one of the unique features about is llatriv is that it has a long intracellular halflife. That means it can actually be spaced out to dosing less frequently than once a day. So in combination with lenapir we're looking at oral once weekly dosing and we're working with uh Gilead on a phase three program right now and we have two clinical trials the island one and island two studies that are going to be reading out shortly and having um results sometime mid this year.

[00:18:18]>> So results that might be ready in time for the international AIDS conference in Rio >> maybe.

[00:18:25]Okay, stay tuned folks. Um, is it would it be beneficial for people who um, say are taking advo working well for them to then if something like Islap come out to kind of know, okay, this works well with my body.

[00:18:43]>> Yeah, that's a great question. So to answer that, let me talk about our other internal once weekly treatment combination that also includes is latche. So this one is a combination of is latche with ulanverine and if you can maybe tell by the stem duravine ulanverine these are both NNRTI and they're similar to each other but ulanverine can be dosed once weekly with once weekly is latche so actually that's the natural transition if you're doing well onzo which is a combination of is ladvere and davverine you could potentially switch if the data are supportive and are phase three studies that are that are in the works uh as we're planning them now that you would move to is latche in combination with ulaverine which would be a once weekly oral regimen.

[00:19:33]>> Okay, great. Another potential weekly option. You mentioned that the clinical trials are in the works now. Are you recruiting actively?

[00:19:43]>> Yeah, great question. So we are nearing the end of our first phase two study with Islaine and you'll have to stay tuned on this one as well. So we'll have some results mid year on that phase 2 study which is in verologically suppressed people on victar switching to islatravir ulaverine in phase two and if positive that would support us moving to the verologically suppressed population in phase three.

[00:20:10]I'll also say that we are currently recruiting right now for Islaine in a phase two study in the treatment naive population. So that's the study that's ongoing and enrolling right now.

[00:20:22]>> So people who are newly diagnosed and have not been on treatment yet, you're actively recruiting for. Is there a way that if someone is watching this and wants to contribute that they can participate or seek out?

[00:20:34]>> Yeah.

[00:20:34]>> Where they might be able to participate?

[00:20:36]Yeah, the easiest way to do that I'll share with you the NCT number which you can go and clinical trials.gov and look up for sites that are may be close by.

[00:20:47]>> I will um I will have the NCT number in the description box below as well as this link so you guys can look it up if you're interested.

[00:20:56]>> Great.

[00:20:56]>> Well, that's some really cool exciting information. Uh the other thing I wanted to touch on that's um more prevention is your lung acting prep and the study I believe is entitled MK8527. Can you talk a little bit about that? Yeah. So we lock we talked a lot today about is latcher based new treatments for HIV and we have an exciting new program uh that's in phase three and two large studies that are assessing 8527 which is related to Islier and has potential to be a monthly oral prep. Um, and so we really see that this is a potentially transformative um, intervention that may decrease um, a lot of the challenges with imple implementation and adherence with current prep options, whether they're long- acting injectables or daily orals.

[00:21:50]It really fits a sweet spot there and has a lot of potential for uh, HIV prevention. So, in addition to treatment, we do have a really exciting prevention program.

[00:22:00]>> Yeah. Um, I mean, weekly sounds pretty compelling to me. Uh, I haven't quite been inspired yet to pursue any injectables, but weekly is certainly something that would seem like a low lift transition to something that's more convenient. And a monthly, I mean, I I think that's that would be pretty gamechanging for people who are, you know, either on prep or considering prep. And I think it's such such I I can't speak to the importance of having that kind of option where um you don't have to think about it every single day.

[00:22:35]And then also for privacy reasons like to not have to be taking a pill every single day. There's so many situations where people don't want the potential exposure of other people witnessing them taking a pill every day or having a bottle of pills on them to take every day. So um that's really exciting. I think >> yeah I think the future of both treatment and prevention is long acting for and thanks for sharing that Rafe. I think that's really um matching what we're seeing and hearing from the community as well as you know the potential benefits of long acting treatment and prep.

[00:23:08]>> Great. Well Louisa is there anything else you'd like to share that we haven't been able to address yet? I think one thing I'd like to mention, Rafe, is just um as I said, it's been an exciting week since the approval of Envzo and we've been thinking a lot at Merc about our long-standing history in HIV. We've been involved since the beginning of the epidemic since for the past 40 years and we have um a good track record of bringing forward scientific innovation as we think about this approval at Adenzo. It's the next step in our success of the HIV pipeline and really our commitment to the community. So really appreciate you taking the time to speak with me today.

[00:23:46]>> Yeah. And really appreciate you um being willing to bring in community um and connect with with to be able to connect with science and kind of uh answer some questions and also kind of give some insight into your pipeline.

[00:24:02]>> Really happy to do it. It's my pleasure.

[00:24:04]>> Louisa, thank you so much for taking the time to sit down with me and chat today.

[00:24:08]Everyone at home, please comment below your thoughts, questions, concerns. I'm happy to follow up. I'm sure we'll have some follow-ups coming up this year, hopefully. And um don't forget to like, subscribe, hit that bell so you get a notification every time a new video comes out. 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.

[00:24:27]All right, until next time. Cheers. Bye, Louisa.

[00:24:30]>> Bye. Thank you, Rafe.

[00:24:37]Lord, it's those guys.

[00:24:42]Yeah.