Welcome to the 2024 Jefferies Healthcare Conference. It's my pleasure to now introduce John Butler, the CEO of Akebia Therapeutics. Thank you.
Thank you so much. Thank you very much for the invitation to the Jefferies folks to present to you today. Very happy to be here to talk about Akebia Therapeutics. I just want to remind everyone that I'm going to be making forward-looking statements, so please refer to our SEC filings for more information. It is an incredibly exciting time at Akebia. After a very, very long road, we are within weeks of introducing our second commercial product, Vafseo, to the market. We are a fully integrated company with a focus on kidney disease, and Vafseo is an important product to treat anemia of CKD in patients on dialysis. You know, it's been such a long road for us. You know, you feel like it's time for a victory lap, but we're way too focused on making our launch a success.
That is what the entire company is focused on today. The other thing that's quite exciting that we're on the verge of, we hope, is understanding with the FDA a path for bringing Vafseo to patients with chronic kidney disease who are not on dialysis. This is a very large market opportunity, much larger, at least twice as large as the dialysis opportunity, which in itself is a billion-dollar opportunity. I think we'll spend 90-plus% of the time in the presentation today talking about Vafseo, our launch, and the NDD opportunity. But we're also excited about some of our early-stage programs. We really think that HIF creates a platform where there are serious diseases that can benefit from treatments, and we have two molecules that we're moving into the clinic, hopefully over the next 12-plus months.
You know, we are excited about continuing to help patients with kidney disease as we build this company. Let's talk about Vafseo. Again, Vafseo vadadustat is indicated for the treatment of anemia of chronic kidney disease in patients who are on dialysis. This is a hypoxia-inducible factor prolyl hydroxylase inhibitor, or a HIF-PHI, or we talk about it being a HIF. This is a very unique mechanism of action. It's the mechanism of action that allows for a much more physiologic approach to treating anemia. This is what has nephrologists and physicians excited about using this product, rather than the erythropoiesis-stimulating agents or ESAs that they've been using for the last 30 years. They have a new way of treating anemia. You know, it activates a physiologic response in the body, the physiologic response to changes in altitude. The drug's now approved in 37 countries.
It's been in Japan for over three years now. It's being introduced in Europe as we speak, and of course the most significant opportunity for us is to bring the product to the U.S. We announced our WAC pricing in the U.S., which is about $15,500 per year for a patient, and this is critically important pricing. It's always critically important, but as we think about the dialysis market and navigating that market, it's even more important to really understand the impact of pricing there. We really think a competitive advantage for the company is our expertise in renal disease, particularly in dialysis. We have a commercial organization that's fully staffed. Recall, we have a product already, Auryxia phosphate binder, that the commercial folks have been selling for a number of years. The team is fully staffed.
As of the fourth quarter, they are fully focused on Vafseo and having that product come out of the gates in a successful way. We're covering 100% of the target nephrologists with our commercial organization. Our account team, the account team is responsible for contracting with the dialysis providers. They have 20+ years of product launch experience in nephrology. I think it focuses on the plus. These are folks who have deep, deep relationships with dialysis providers, which you absolutely need to be competitive in this space. Medical affairs is incredibly important to our success here as well. Not only do you have to have the contract, then you have to have a protocol in place for how the physicians will be able to use the product in the dialysis center.
Again, an extremely experienced medical affairs team led by a nephrologist who has worked at dialysis organizations and has treated these patients and has incredible credibility with the dialysis providers. And we have relationships with KMEs that go back decades. And, you know, we're really quite excited, and I think they're quite excited for us and for the patients. So what do we have to do to be successful in our launch? Really, three things that we have to focus on. We have to create access, drive demand, and build evidence. And we're focused on all of those. You know, in every launch, I think you first have to drive access. Access is critical. But normally, when you're talking about a Part D drug or one with a lot of commercial patients, you know, you're thinking about contracting with insurers. You have to think differently about dialysis.
I'll just kind of step you through that now. Because Vafseo treats anemia in dialysis patients, it falls under the dialysis bundle in the U.S. Because it is an innovative new product, it gets two years of a separate payment at an ASP price because it's an innovative new product. Then for three years following that first two years, and that's what we call a TDAPA period or a transitional drug add-on payment adjustment, after that, there's three more years of an extra payment to the dialysis provider. You know, basically what that creates, and CMS created this payment system because they knew that in a bundled environment, it's very difficult to try new and innovative drugs. That's why TDAPA was created, and that's what we're going to have the opportunity to take advantage of.
One of the things you have to remember about dialysis patients and anemia is 90% of them are treated with an ESA today. TDAPA really works when you have a disease that is so dominant in the patient population. And we really do believe we're going to be able to take advantage of that. So how do we do that? Well, instead of contracting with insurance companies, we have to contract directly with the dialysis providers. They're the ones who are going to be buying Vafseo. And the contracts are going to be really pretty straightforward. There'll be an off-invoice discount and then a volume-based discount. So the way to think about it, I always get the question, well, what's the gross-to-net going to be? Well, as the volume of Vafseo sales grow, as we treat more patients, our discount will increase.
Our average price will increase, but of course, we're still going to be benefiting greatly from the increased volume. So, and having that rebate allows you to manage the ASP, which is what the dialysis provider is reimbursed on. The other thing that's critically important for the dialysis providers is at the end of that TDAPA period, they have to have price predictability. What does that mean? It means they pay a certain rate for ESAs today as part of their dialysis bundle. They have to know that the price they'll pay for Vafseo post-TDAPA will be the same as what they're paying for ESAs today. Now, that means we have to take a discount in the price when we get to past the TDAPA period. But this is a billion-dollar market opportunity today for the ESA.
So this is an opportunity that we can have a significant amount of success in post-TDAPA. So we're really quite focused on making access for as many patients as we possibly can, and the team is making great progress. We have a number of dialysis providers under contract today representing about 60% of the patients that are treated or about 340,000 of the 550,000 dialysis patients. Now, our goal is to have 100% coverage by the end of the year. Remember, there's two dialysis providers that treat about 70% of the dialysis patients. So as you can see from the numbers, it's really one of the large providers that we still have to contract with. We're working on that. And again, our goal is to have it done by the end of the year.
I look at that 340,000 patients, and I know that we have a lot to do and a lot of opportunity when we kind of cross that finish line and ship the first bottles in January. You know, you can have the best contracts in place. You can have a great financial incentive for the dialysis providers. And make no mistake, TDAPA creates that financial incentive. When you think about, I'm paid a bundled payment today that includes my ESA. When I incorporate Vafseo, I avoid the cost of the ESA, and I make the spread on the Vafseo contract. There's a great financial incentive for dialysis providers. You can have all the incentive in the world. If the physicians don't want to use the product, it's not going to be used.
And that's why we're so excited about the most recent market research data that we've generated that says 92% of nephrologists in the survey plan to use a HIF. 27% plan to use it in the first three months. Now, you know, I've launched a lot of drugs in nephrology, and I would say nephrologists aren't like oncologists. I mean, they are generally more slow to adopt new drugs. So, you know, what that 92 and 27 really turn out to be, we're not sure. But I have to say, I've never started from that kind of a base before. And, you know, when you pair that with the, you know, the financial opportunity here, we do believe that people will want to use Vafseo. And what are the reasons that physicians are giving for this incredible excitement about it?
They've been using ESAs since Epogen was launched in 1989. What's the difference? Where are the areas that they feel there's an unmet need? They're looking for an orally administered drug. Vafseo is an oral product given once a day. They want this natural physiology. They want to avoid excursions of hemoglobin and fluctuations of hemoglobin that they see with the way they are treating patients with ESAs today. And they really want to avoid the overshoots, because that's the overshoots, meaning hemoglobins that go above their target. That's where they worry about MACE risk and safety risk. And at the end of the day, when you look at the data for Vafseo, you have many fewer dose titrations. They spend a lot of time titrating their ESA dose, you know, constantly to keep patients in the range.
In all of our studies, you had many fewer dose titrations with Vafseo. Well, that means it's easier for the nephrologist to use, and you should never minimize the value of something that makes their life easier. So physicians are there. They're interested in using the product. We want to drive Vafseo. Our ultimate goal is to become standard of care for patients on dialysis. But you always have to start somewhere. So where is it that physicians are looking to use the product today? We've been talking about this for some time, and physicians constantly give us that same feedback. There are two areas where they're particularly interested in using the product. In the home dialysis population, these are patients who now have to come in to get an infusion or injection of an ESA at least once, sometimes twice a month.
Giving them an oral daily pill is much easier for the patient, avoids them having to come into the center as frequently. They really see that as an advantage. That's about 80,000 patients in the U.S. Now, the other area is in patients who are on the highest ESA doses, and that's about 150,000 patients. Now, again, as your ESA dose increases, in every study that's been done, you see MACE risk increase as well, so with Vafseo in our phase three study, whatever the dose of Vafseo, you didn't see an increased MACE risk. It stayed consistent over time. That's interesting to physicians. The other thing, of course, is that, remember, they're getting a bundled payment that doesn't change based on the dose of ESA that they're providing, so when you think about the highest dose ESA patients, those are also the most expensive patients for the dialysis provider.
So to avoid that expense and be able to charge for or bill for Vafseo separately makes that a compelling economic argument as well. But remember, it's always grounded in a strong clinical rationale to use the product. The third area where we have to continue to work is to build evidence for the product. You don't become standard of care unless you continue to invest in clinical results. Now, the data that we're launching the product with is very robust. And, you know, we think we can have a very successful launch. The INNO2VATE program, our phase 3 study in dialysis, as well as our non-dialysis program, PRO2TECT, are published in the New England Journal of Medicine.
There's a great article in the Journal of Hematology that's a review of this differentiated mechanism that really focuses on things like the fact that HIF activates iron and utilizes iron more effectively. These are the kind of things that are incredibly interesting for physicians and differentiate us from current treatments. Just last week, we announced that in the American Journal of Kidney Diseases, we had published our FOCUS study results. Again, our label for Vafseo is once-daily dosing. For patients in center, physicians are very interested in being able to give the drug when patients come in for dialysis, which is three times a week. We ran a study of about 450 patients called FOCUS, where we treated patients in just that manner. We gave them three times weekly dosing versus Mircera, a long-acting ESA, and demonstrated that you could very successfully dose Vafseo three times a week.
Ultimately, we will go to the FDA to add that dosing regimen to our label, but the publication is important for physicians to make the decision of how they want to dose the drug. The focus data is really quite important as we think about building additional evidence for the use of Vafseo. If you look at the graph on the left here, this is the efficacy graph, and Vafseo is the blue line. You see that when you dose patients three times a week using their baseline ESA dose as a particular starting dose, you see you maintain them in the target range beautifully across the entire study. In the INNO2VATE study, our pivotal phase III, we used a single starting dose of 300 milligrams. There was a concern from the FDA that if we used a higher dose, you'd see hemoglobins go too high.
Well, what happened there was you actually saw patients, if they were on a high baseline ESA dose, you saw their hemoglobins drop. We had time to titrate them. Remember, it's a titratable drug, so we very successfully hit our primary efficacy endpoint. But during that downtime for hemoglobin, physicians might want to rescue them with ESA because they worry about the hemoglobin going too far down too quickly. Well, when you looked at ESA rescue in the INNO2VATE study, you saw that there was really no difference between darbepoetin and Vafseo, even though they were doing more ESA rescue in the early days, in the first 12 weeks of the study.
Well, if you look at the data from FOCUS, when you get that starting dose right and you maintain hemoglobin through the titration period, if you look at the chart on the right, you see that you significantly reduce ESA rescue. If you look at a 100% increase in ESA dose, which is three times what they're supposed to increase the dose by, and you find that as ESA rescue, you still have about a 50% reduction in rescue. Why is that important? Well, when you looked at MACE and the probability of MACE in INNO2VATE, two of the things that were most closely correlated with increased MACE risk was excursions of hemoglobin above target range, where we were always better than the ESA, and the incidence of ESA rescue. So in INNO2VATE, we demonstrated about a 6% reduction in all-cause hospitalization. That wasn't statistically significant.
But we felt that with this three-times-weekly dosing, particularly reducing that MACE risk, can we actually see an improvement in all-cause hospitalization? And we are on the verge of initiating the study in collaboration with U.S. Renal Care, the third largest dialysis provider, and Dr. Jeff Block, who's an outstanding trialist. And we're looking at this is a trial called VOICE, and we're looking at all-cause mortality and all-cause hospitalization in about 2,200 patients. The objective here is that if we reduce all-cause hospitalization by 10%, we're powered for statistical significance. Now, as you think about how you become standard of care, it's generating this kind of data. We are, again, just on the verge of initiating this trial. The hope is that we can complete this trial around the time our TDAPA period ends or just after that and quickly publish positive data from this study.
If you're reducing hospitalization, you're saving costs for the dialysis provider, and of course, staying out of the hospital is a huge benefit for patients as well. We're incredibly excited about the potential for this trial, and we are working on complementary kinds of trials, probably not the same size as this with other large dialysis providers, to continue to generate data to move towards standard of care, and one thing I think it's important to point out, you know, this seems like it is a large study and an important study, but because of the collaborative nature and, you know, working with Jeff Block, who we've worked with on multiple studies in the past, we're doing this for an incredibly efficient cost as well, so that's the dialysis launch we're excited about. As I said, we're incredibly focused on this as a company.
We think that there's a massive opportunity to drive value for Akebia in the non-dialysis population. You know, I talked about, you know, talking about with physicians about where they want to use the product. And, you know, they'll say in home patients and high ESA, invariably they end with, "But I really would like to use it in my CKD patients who are not on dialysis yet." It's a once-a-day oral product. Three out of four patients today who have anemia who are stage three or stage four, and that's about the same size as the dialysis market, a little over 500,000 patients, three out of four are not treated today. The patient doesn't want to come in for an injection. Insurance issues. If their hemoglobin's at 10, they can't get another shot, so they miss a shot. Three out of four are not treated today.
And we know that there's a significant increase in mortality risk if they're not treated. There's a significant increase in transfusion utilization. It amazes me that in 2024, physicians will still transfuse patients when they come in with hemoglobins below nine. And of course, a blood transfusion for a patient who's a non-dialysis patient reduces the possibility that they'll be able to get a transplant, which is, you know, obviously an outcome that no one wants. Physicians dominantly, they see the ability to write a once-a-day oral drug for this non-dialysis population as a huge benefit. And we are quite committed to pursuing that opportunity. This slide just demonstrates that. The graph on the left, you see that the mortality rate when you compare a patient with a low hemoglobin to a patient with an over nine hemoglobin is bad when they start dialysis.
But even 12 months later, when they've been treated and their anemia managed, they still have a higher mortality rate. So if you don't start them out right, they never catch up. So, you know, we think this is compelling. The FDA agrees that this is an extremely unmet medical need. And right now, we are engaging with the FDA on a path forward. We know we're going to have to do more clinical work to have a path forward for the non-dialysis population. We hope by the end of this year, we have an expectation that we'll be able to communicate to the market what that path forward might be. Now, we know this will be an ongoing dialogue with the agency, and it'll always be a review issue at the end of the day.
But to be able to communicate, "This is the study we're going to start, when we're going to start it, what it's going to look like," we think is going to be an incredibly important moment for the company. If you recall, PRO2TECT, we did not meet our primary endpoint in our non-dialysis trial. But if you looked at the U.S. patients, the U.S. patients, which were about 1,300 patients in the study, where non-dialysis patients were treated in a much more homogeneous manner, we did demonstrate that hazard ratio of 1.06 and barely missed the upper bound, which we were targeting at 1.25 at 1.28. So, you know, we think that there is clearly a path. We look forward to working with the FDA on defining that and being able to talk to you about it. You know, I'm going to run out of time here.
There's so much more that we're excited to talk about. I'm glad we spent most of the time on our launch and our non-dialysis opportunity. But we do think the HIF pathway creates other opportunities as well. We have a new compound, AKB-9090, that's in preclinical tox work now that we expect to have enter phase one testing next year. Our first indication that we're targeting is acute kidney injury and ARDS as a secondary indication as well. And following shortly behind that is AKB-10108, which is a product I'm incredibly excited about. And this is targeted at retinopathy of prematurity. Remember, HIF, anything that involves oxygen, the opportunity exists for the product there. And we look forward to coming back and talking to you about it more as well. We're doing all of this from a position of financial strength. Remember, we have the Auryxia revenue behind us.
Proforma, last quarter, we had about $43 million in the bank. We expect about $40 million of revenue this quarter from Auryxia. And of course, with Vafseo revenues then now being added to the company, we believe we can advance our pipeline and a significant return to shareholders. So, you know, we have a catalyst-rich coming months. We can't wait to start talking to you about how quickly we'll get out of the gates with our Vafseo launch in January, talk to you about the FDA progress that we make, the initiation of VOICE, and moving our pipeline forward. So thanks for your time and attention today.