Okay. Welcome, everyone, to Jefferies London Healthcare Conference 2025. My name is Roger Song, one of the senior analysts covering MedCap in the U.S. It's my pleasure to have the fireside chat with our next company, Akebia. Welcome, John and Eric.
Roger, thanks for the invitation.
Awesome. Already, I think we have a lot to cover, and then particularly with your exciting launch for Vafseo in the dialysis patient. Maybe just give us some recap of how the launch so far is looking like, and then any surprise or happiness you have experienced so far.
Surprises or happiness. As you mentioned, we launched Vafseo, or vadadustat, our HIF-PHI for treating anemia patients on dialysis in January. We are very, very pleased with the progress of the launch. As you know, we got off to a great start, mostly in U.S. Renal Care, which is the third-largest dialysis provider, and great clinical advocacy there from the Chief Medical Officer group at U.S. Renal. We have continued to make great progress, both at U.S. Renal and across other dialysis providers as well. Dialysis is a complicated business. It is a frequently slow business, but ultimately, it is the differentiation of the product, the clinical benefit, the unique aspects of this HIF-PHI versus the ESAs that they have been using that we believe is going to make this product standard of care. We have made progress. The two biggest dialysis providers are Fresenius and DaVita.
Fresenius is definitely taking longer. DaVita is really making nice progress as well. They had a pilot that they started in August. Big behemoth of a company does a pilot because they have lots of operational complexity, which we experienced through the pilot, but they were very pleased with how it went. They opened the product up to all of their dialysis centers as of November 10. We expect that through the balance of the year, they'll kind of work through going from 100 centers to 4,000+ . I'm sure we'll carry other kinks, but we think we're going to be in a great position starting in 2026. I mean, we spent most of the first half of the year with access to about 40,000 dialysis patients.
We're going to be leaving this year with access to, I mean, today we have 260,000, hopefully 275,000 by the time we leave the year. So we're really happy with how that's progressed, though I'm never happy that it's not going faster.
Yeah. As you said, launch a drug as a MedCap biotech is always challenging. In the dialysis patient population, it is expected to be slow, but also we are so confident about the drug profile, so we think it can be going faster, but it may eventually catch up.
Oh, it will. I mean, there's no question in my mind that it will. I mean, usually when you have these concerns, it's because the prescribers are still needing to be convinced. And we certainly have to do that to an extent, but you look at the prescribers want to prescribe the drug, they need to get access. When you throw the dialysis provider as the middleman into the middle of this and you have to work through all of their operational systems, it's just time-consuming, but it's just operational, right? It gets resolved, and then patients get drug, and that's what it's all about.
Yeah. Yeah. We'll talk a little bit of kind of detailed dynamic here, but also we want to set the expectation right. You mentioned the growth. You're fully expecting the growth into 2026. How should we think about the 4Q and then how much growth you want to guide to the market?
Yeah.
Not too high off the top.
Yeah. No, I mean, we're not giving revenue guidance, but as we said, as you think about 4Q, there's a couple of dynamics that I think are important. On the positive side, we had the fourth largest dialysis provider, DCI, that we said they made the product widely available in the middle of August, but that's when they really started training everyone. So it really was, it's really now just been available to folks. We do certainly expect that to start to kick in. As I said, the bigger provider is DaVita, and they've made it available, but you just see the way the kind of the stumbling blocks of, for instance, they had a doctor wrote a prescription, then it has to get reimbursement approval because of this TDAPA reimbursement. They have to ensure that a patient can get that insurance.
There was a problem with the one system talking to the other, and they fixed it. All of these little things kind of add up for us. Again, not an issue around physician prescribing, but that, I think as you go from 100 to 4,000 centers, we'll probably see more of those little bumps in the road. The other thing, U.S. Renal has really been the one that's been contributing most of the patients that are on drug today. They are moving to a place where they're offering treatment on a TIW basis. Recall, Vafseo is a once-daily oral drug. They're sending the drug to the patient's home and having them take it.
They've had patients come off the drug because they would see a dip in hemoglobin and the anemia manager would be worried about the patient taking the drug, but automatically switch them. They recognize one of the ways to deal with that adherence issue, because again, that's an operational issue. It's not a drug performance issue, is to offer the drug three times a week, which they can do. There's data to support that. It's not in our label, but they're choosing to make that change. I see them, they're starting that now. They've rolled it out to, I think, 100 or so centers at U.S. Renal Care, but they'll go to all 400 and something centers by the beginning of next year. I could see that if I'm a doc at a U.S. Renal Care center this month, next month, I want to put a patient on.
I said, well, you know, but I can do TIW dosing come January 1. You may wait and start that patient then. And then we have this issue around inventory, right? Where they have 150 milligram tablets now that they ship to the patient's home. They're bringing that inventory down because they're going to use 300 milligram tablets dosing in the center. And again, that's a shorter supply chain, so they don't offset each other. So again, something that's just unique to the fourth quarter, but may have an impact on the quarterly revenue. But again, the long-term moving people to TIW dosing, I think, is the best thing for their patients and is very good for our long-term business.
Yeah. Yeah. Because when we look at the metrics from Q to Q, it seems your prescriber is stable. Also, because the access is not dramatically growing before the DaVita and then RC. Also, the prescription per prescriber seems a little bit lower for the 3Q. That is what you said in terms of refill and adherence. Maybe you mentioned TIW. Maybe just summarize for us, what are the key strategies you can make sure the refill adherence rate can go back to, I think, 70%-80% of industry kind of a standard or another goal for you to get there?
Yeah. As you said, our prescriber base was reasonably flat from Q2 to Q3, but it's still mostly coming from U.S. Renal. And 85% of U.S. Renal docs have written a prescription for Vafseo, right? I mean, that kind of penetration, we're really pleased with. Again, you have kind of that situation where a lot of the discontinuations come before a patient even gets a second prescription. That's more driven by the anemia manager saying, oh, I've seen a hemoglobin drop by half a gram per deciliter. They're used to, for 35 years, they've given people a shot in the center and they know exactly how it works. We've sent this home for the patient. Now I'm worried, I get incented on keeping people in the range. Let me switch quickly. A lot of education.
We're seeing those numbers change slowly, but the ability to give the patient the drug in the chair really, I think, is going to make a big difference for the prescribers. We've seen some of those patients, small numbers, but some of those patients who were taken off the drug, put back on again. I think we'll see even more of that as they move more broadly into TIW. US Renal, they're huge advocates. They're going to continue to grow. There's room to grow there, no question. It's really driving that demand at DaVita, IRC, DCI, and ultimately Fresenius that will make the drug standard of care.
Okay. Basically, using the TIW, it's more in line with the current practice and they can see those patients, if they have any concern, and then they can adjust immediately.
It's observed dosing, right? I mean, we know you give the drug once a day. For the home dialysis patients, which is about 15% of the population, they'll still do that. I think they just, as you said, I mean, EPO for however many years, you give them a shot each time they sit in the chair and you know they're getting treated. Observed dosing is something they don't have to worry about the patient's adherence. You have two or three, whatever the dose is, 300 milligram tablets, you hand it to them, they take it. I know they're being treated. You can manage things like any concerns about GI tolerability issues, because it's an oral drug. They can manage that. We're seeing that being managed very, very well, particularly when someone uses TIW.
I think all of them will ultimately go there because the data really supports it. We're not promoting it there because it's not in our label. They're making the decision based on the data that exists to do TIW dosing.
Tell us about the data because I think you had some updated data at the ASN just a couple of weeks ago, and then that seems supporting the TIW.
It's interesting. There is a study called Focus that is published, about 500 patients, TIW dosing, and the drug performed very, very well. You have a slightly longer half-life, obviously, in dialysis patients. It seems like allowing them kind of that break, it actually could be a better dosing regimen for the patient. The data we presented at ASN, that was with QD dosing, with everyday dosing. This was an analysis of the Innovate data, which was our phase III study, which was a QD study. This is the data that we keep talking about this product becoming standard of care. I think this is the data that gets you there, right? The kind of data. This was basically this win odds analysis just brings a lot more statistical power to an outcomes data set.
We had about 3,500 patients in the INNO2VATE study, 1,750 versus 1,750. What the win odds analysis does is it compares each patient against each patient. You end up with about 3 million data points in a study of this size. When we did INNO2VATE, we had about a 1% lower mortality rate and about an 8% lower hospitalization rate. Most of the hospitalization was associated with MACE. When we do this hierarchical analysis where being alive is better than being dead, being out of the hospital is better than being in the hospital, et cetera, we end up with a statistically significant lower risk of dying or being hospitalized when you are treated with Vafseo or vadadustat versus darbepoetin. When you look at an on-treatment analysis, which is important to the agency, that P value becomes like 0.0001. It is clearly statistically significant.
Now, we have the VOICE trial that's ongoing that Dr. Jeff Block from U.S. Renal Care is the primary investigator for. He has adopted that same win odds analysis as the primary endpoint for VOICE. So that's a TIW study.
That's a TIW, yeah.
That's going to be, so we'll have prospective confirmation of what was a post hoc analysis from Innovate. Between those studies, we have the vocal study, which is also a TIW study, which we're doing with DaVita, which is looking at, it's a smaller study, 350 patients, but there's actually a smaller sub-study where we're looking at the quality of the red blood cell. There's data that exists around the difference in the red blood cell that's made with HIF versus made with an ESA. We're going to look at all of the omics, kind of the hemoglobin carrying, how it moves through capillaries, some really interesting data that really confirms for prescribers that this is a different way. This is a more physical, we always say there's a more physiologic way of managing anemia.
You are going to get a more physiologic red blood cell as well. Those are kind of really strong reasons to believe for docs. We will have that data in the fourth quarter of 2026, followed hopefully early in 2027 with the VOICE data that confirms that there is an outcomes difference here as well. That is how you become standard of care, you continue to generate data like that.
Yeah. Now, in the hospitalization rates that John mentioned, besides obviously being great for the patient, it's important to note that from an economic perspective, that's important to the DOs because when dialysis patients are bussed to the hospital for a period of time, the DOs share in a portion of those costs.
Yes. Yes. The TIW, the profile you really want to achieve is hemoglobin control, side effects, and then the outcome. Equivalent, if not better than the QD and then the standard of care.
Yeah.
Yeah. We clearly showed that you can manage the hemoglobin levels with either dosing regimen. That's no one's, it's not an efficacy issue at all. It is a, the doses are slightly lower when you use TIW, but the compliance is higher because they get it every time they sit in the chair versus no patient is perfectly compliant. I'm not perfectly compliant with anything that I'm supposed to take. That's kind of a wash. From a provider perspective, an anemia manager, the physician, when I can see the patient take the drug, I feel, I definitely feel better that I know they're getting their anemia treated.
Yes. The overall exposure level. One thing I picked up during our previous conversation is this physician-driven sales versus a U.S. Renal Care center because they are a little bit more top-down. Just tell us a little bit more about, because you do have the middleman, the DO organization versus physician level.
Yeah. Yeah. That was just an important way to think about adoption. We got out of the chutes so quickly because you had this great advocacy from the CMO office at U.S. Renal. They recognized that with TDAPA, there was an economic incentive as well, but it is always driven by clinical needs. You had a push, right? They actually kind of basically, here is all the patients that are reimbursed. Doctor can always do what they want, but they were encouraging them to write prescriptions. We saw that great start. On the U.S. question, will we see the same thing out of DaVita or the others? For the most part, they are making it available, but they are leaving it up to the physician, right? It is, I mean, we have a commercial organization.
Their job is to communicate to the prescribers and get them to prescribe. It is a more traditional, this is how drugs are adopted versus the push, right? It is not like DaVita is going to say, here are the 100 and whatever thousand patients who are reimbursed, go put them all on. They are going to say, let us let them come to us. If the physician wants to prescribe, they can. What is your strategy?
Yeah. What's your strategy to get those patients?
We have a commercial organization. That's what we're paying them for. I mean, that is, they're out there communicating. And frankly, they've been doing that with DaVita physicians and the DaVita physicians have wanted to write the drug. So they have just, even at the pilot, you experience that, okay, I want to write the drug, then you have an issue with this system talking to that system. It all seems to be worked out, but I'm quite nervous about going to scale that we'll just see some of that. I hope all of that gets worked out over the course of the fourth quarter so that everyone feels comfortable going into January that their patients can get it. And we have our commercial folks are focused on physicians who are seeing patients at DaVita centers, not spending a lot of time with people who are in Fresenius centers.
Hopefully that focus will pay off in patients getting on as quickly as possible.
Yeah. Another dynamic we mentioned a couple of times is the TDAPA, right? You have a three-year TDAPA period. I understand the very certain population you can get access is the fee-for-service patient. You do get some indication or at least some portion is coming from the Medicare Advantage. Maybe tell us how you think this population may grow in the second half of the TDAPA period and how this will have some indication into the post-TDAPA kind of period.
Yeah. About 30% of our prescriptions are being written for Medicare Advantage patients. If you think about dialysis, about 85% of the patients are Medicare, about half are fee-for-service, half Medicare Advantage. TDAPA is clearly for fee-for-service, but someone like DaVita has a lot more leverage with MA plans and they can get coverage. I do expect to see that grow. We love the TDAPA period because we actually have a higher price per patient. That price will come down substantively in the post-TDAPA world. Recall that's still a billion-dollar market today. Even at $2,500 or $2,000 per patient, it's a billion-dollar market. We will have access to everyone, right? Now, you're clearly not having all of the market. Post-TDAPA will have all of the market. Anyone can get it. You don't have to confirm insurance like they have to do now.
I mean, we want to get as many patients on during the TDAPA period as possible, obviously, to increase revenue. It's good for the patient and we're in a better position post-TDAPA. The nice thing about the post-TDAPA period will be that every patient can get access to the drug, albeit at a lower price per patient for us.
Do you have any anecdotes from the physician? They say, yeah, so I really like Vafseo even after the TDAPA period and then they are willing to continue to prescribe.
Oh, I mean, this is, no one's thinking about this. There are drugs that are TDAPA plays, right? That there's nothing in the bundle and therefore they use it during TDAPA and then they stop using it, right? That's never been the way we've approached this. We've always approached this thinking about the long game. We wouldn't be supporting the kinds of clinical development that we are. Docs want to use this drug because they absolutely believe there's a difference in treating patients with a HIF versus treating with an ESA. You've heard people talk about that ESAs can be toxic. This is a more physiologic approach. This is, again, there's work to do to get there, but this will be standard of care. You can't become standard of care if people can't access the drug.
I look at a billion-dollar market, standard of care would be at least half the market, right? That's at least a $500- million drug. Obviously our sights are set even higher than that.
Yeah, sure. All right. A couple more minutes and then we can talk a little bit about the pipeline outside of the dialysis launch. Recently you got some surprising feedback from the FDA for the NDD patient population. Tell us about maybe the next step for that population because it's obviously a very big opportunity. You do have a long kind of a pipeline, earlier pipeline. How should we think about that?
Yeah. NDD was surprising, was disappointing conversation with the FDA. What they wanted from a size of study just did not make sense for us. They were engaged in subpopulations. We think it is, I mean, we are most upset from a patient perspective. Doctors at ASN, they are angry. They want to use the drug in the CKD population. We are going to keep engaging with the FDA on the subpopulations. If we can get some NDD in the label, we think that would be helpful for patients. As I said to the company, I said, we have a really interesting pipeline of things that we have more things to spend money on than we have money to spend. What we have talked mostly about is our early stage pipeline. We have a product, AKB- 9090, which will be for acute kidney injury.
It will go into its first normal volunteers, first in man studies in the early part of next year. We have a product for retinopathy of prematurity, which is a little further behind. These are both HIF-based compounds. We have some other things that we haven't talked as much about publicly that we look forward to starting to talk more about.
Excellent. Okay. Maybe Eric, in terms of the financials and how you think about the balance sheet right now and then how does that support the launch and the pipeline development?
Yeah, sure. We have a strong balance sheet, $166 million in cash as of the end of Q3. We've guided that we're financed to profitability. That guidance takes into account estimated revenues as well as expenses related to advancing the existing pipeline.
Excellent. We should end this fireside chat with a path to profitability for Akebia.
Perfect.
All right.
Thanks again.
Okay. Great. Thank you. Thank you for the time.
Thank you.
Thank you.
Awesome.
Man. Right on time, I think.
Yeah, right on time.
That thing goes crazy.