Good morning. My name is Michelle, and I will be your conference operator today. At this time, I would like to welcome everyone to the Biogen Idec and Sobi Hemophilia Conference Call. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question-and-answer session. If you would like to ask a question during this time, simply press star then the number one on your telephone's keypad. If you would like to withdraw your question, please press the pound key. I would now like to turn the call over to Kia Khaleghpour. Please go ahead.
Good morning, and thank you for joining us on today's call. Before we begin, I encourage everyone to go to the investor section of biogenidec.com to find the press release that follows the discussion related to this call. As usual, we'll start with the safe harbor statements. Comments made on this conference call include forward-looking statements, including statements about the development and commercialization of long-acting factors eight and nine that are subject to risk and uncertainty. Words such as believe, expect, may, plan, will, or similar expressions are intended to identify such statements. Actual results could differ materially from our expectations, and you should carefully review the risk and uncertainties that are described in the risk factor section of our most recent annual and quarterly reports filed with the SEC. We do not undertake any obligation to publicly update any forward-looking statements.
As a reminder, the focus of this call is the A-LONG and B-LONG top-line results, and we ask that you limit your questions to the study results. Today on the call, I'm joined by Dr. Doug Williams, Executive Vice President of Research and Development, and for the Q&A portion of the call, we are joined by Dr. Glenn Pierce, Senior Vice President of Global Medical Affairs, and Dr. Birgitte Volck, Senior Vice President, Development Chief Medical Officer of Swedish Orphan Biovitrum. Also joining us in the room is Claudine Prow, Vice President of Investor Relations. With that, I'll now pass the call over to Doug.
Thank you, Kia, and thank you all for joining us this morning. Earlier this morning, we announced positive top-line results from A-LONG, the registrational study of long-lasting recombinant Factor VIII Fc fusion protein in people with hemophilia A. We're pleased with these results and believe the data, along with those from B-LONG, which we released previously, will offer new potential therapies for hemophilia patients. On this call, we'll review top-line data from both trials. Our investigational recombinant Factor VIII and Factor IX molecules are clotting factors developed using Biogen Idec's novel and proprietary monomeric Fc fusion technology, which makes use of a natural pathway used by antibodies to recycle the molecules in the circulation and enables them to remain in the body longer. With this technology, our molecules are designed to provide long-lasting protection from bleeding and may reduce the treatment burden associated with hemophilia.
In the A-LONG and B-LONG studies, respectively, the data showed that long-lasting recombinant Factor VIII Fc and Factor IX Fc prophylactic regimens resulted in low single-digit annualized bleeding rates and were generally well tolerated. No patients developed inhibitors to either study drug, and no cases of anaphylaxis were reported in any patients. Before we recap the top-line results, I'd like to take this opportunity to remind everyone of the study designs. Both studies were global, open-label, multi-center phase 3 studies evaluating the efficacy, safety, and pharmacokinetics of intravenously injected long-lasting Factor VIII or IX Fc. The primary efficacy and safety measures in both studies were the annualized bleeding rate and the incidence of adverse events and inhibitor development. Secondary endpoints included response to treatment of bleeding episodes and direct pharmacokinetic comparisons of recombinant Factor VIII Fc versus ADVATE in A-LONG and recombinant Factor IX Fc versus BENEFIX in B-LONG.
In A-LONG, 165 male severe hemophilia A patients aged 12 and older were enrolled across three treatment arms: individualized prophylaxis, weekly prophylaxis, and episodic or on-demand therapy. In a subgroup of patients across treatment arms, recombinant Factor VIII Fc was also evaluated in the perioperative management of patients who required a major surgical procedure during the study. For the individualized prophylaxis arm, patients received an initial dose of 25 units per kilogram on day one and 50 units on day four. In the weekly prophylaxis arm, patients were treated once weekly with a dose of 65 units per kilogram. The study design allowed for adjustment of the dosing interval and dose to maintain targeted trough factor levels above 1%-3% of normal to prevent bleeding.
In the episodic treatment, patients received treatment as needed for bleeding, while in the perioperative management arm, treatment was evaluated in the surgical setting. A-LONG top-line results showed that the overall median annualized bleeding rates, including spontaneous and traumatic bleeds, were 1.6 in the individualized prophylaxis arm, 3.6 in the weekly prophylaxis arm, and 33.6 in the episodic treatment arm. In the individualized prophylaxis arm, the median dosing interval was 3.5 days. During the last three months on study, 30% of patients in this arm achieved a mean dosing interval of five days. Overall, 98% of bleeding episodes were controlled by one or two injections of Recombinant Factor VIII Fc. Approximate terminal half-life of Recombinant Factor VIII Fc was 19 hours compared to 12.4 hours for ADVATE. Recombinant Factor VIII Fc was generally well tolerated.
No serious adverse events were assessed to be related to study drug by the investigator. The most common adverse events occurring outside of the perioperative management period were nasopharyngitis, joint pain, headache, and upper respiratory tract infection. An average patient receiving prophylactic treatment with current Factor VIII products receives three to four infusions per week and 150 to 180 infusions per year. Our hope is that if recombinant Factor VIII Fc is approved, such patients could potentially go to one to two infusions per week or approximately 50 to 100 infusions per year. We believe the availability of longer-lasting therapies could encourage greater use of prophylaxis in the U.S. than the current estimate of 35%. There are abundant data in the literature to support the value for patients of prophylactic dosing to preserve joint function.
In B-LONG, 123 male hemophilia B patients aged 12 years and older were enrolled across four treatment arms: weekly prophylaxis, individualized interval prophylaxis, episodic treatment, and perioperative management. In the weekly prophylaxis arm, patients were treated with a starting dose of 50 units per kilogram, which was adjusted to maintain trough factor levels sufficient to prevent bleeding. In the individualized interval prophylaxis arm, patients were treated with 100 units per kilogram at an initial interval of 10 days, which was subsequently individualized to maintain trough factor levels sufficient to prevent bleeding. In the episodic treatment arm, patients received treatment as needed for bleeding, while in the perioperative management arm, treatment was evaluated in the surgical setting.
B-LONG top-line results showed that the overall median annualized bleeding rates, including spontaneous and traumatic bleeds, were 2.95 in the weekly prophylaxis arm, 1.38 in the individualized interval prophylaxis arm, and 17.69 in the episodic treatment arm. In the individualized interval prophylaxis arm, the median dosing interval during the last six months on study was 14 days. Over 90% of bleeding episodes were controlled by a single injection of recombinant Factor IX Fc. The approximate terminal half-life of recombinant Factor IX Fc was 82 hours compared to 34 hours for BENEFIX. Recombinant Factor IX Fc was generally well tolerated. The most common adverse events occurring outside of the perioperative management period in the combined prophylactic and episodic treatment arms were nasopharyngitis, influenza, joint pain, upper respiratory infection, hypertension, and headache. One serious adverse event was assessed to be possibly related to study drug by the investigator.
The patient experienced obstructive uropathy in the setting of hematuria, and the patient continued recombinant Factor IX Fc treatment, and the event resolved with medical management. We're gratified by these efficacy and safety results, which demonstrate that recombinant Factor VIII and Factor IX Fc fusion proteins may have the potential to enhance the care of people living with Hemophilia A and B by offering protection from bleeding episodes with reduced treatment burden. We share the enthusiasm of the hemophilia community, including the study participants and clinical study investigators who supported the rapid enrollment of both of these studies. We're eager to complete enrollment in our ongoing pediatric studies, which include the Kids A-LONG for recombinant Factor VIII Fc and Kids B-LONG for recombinant Factor IX Fc, as well as to complete the ongoing extension studies, ASPIRE and B-YOND.
We anticipate presenting detailed data from A-LONG and B-LONG at a future medical meeting, and we're committed to working with the FDA to expeditiously bring both of these long-lasting therapies to hemophilia patients. We expect our BLA submission for Recombinant Factor IX Fc in the first quarter of next year and for Recombinant Factor VIII Fc in the first half of next year.
Thank you, Doug. Operator, we're ready to open up the call for Q&A. We ask that you please limit yourself to one question and then re-enter the queue for follow-up questions. Please state your name and your company affiliation. Operator, we're ready for the first question.
Your first question comes from Michael Yee from RBC Capital Markets. Your line is open.
Hey, thanks. Question is, do you know what % of weekly patients dropped out and what % of patients had no bleeds in the every five-day and the weekly arms?
Yeah, Michael, this is Doug. Glenn and I are going to tag team the questions here, but I'll take the first one. Essentially, we'll provide a lot more and a lot more granularity on the data at an upcoming medical meeting. I think we want to stick to the top-line results today as we did with the factor IX release as well. So I think the median ABR numbers are what we're presenting today, and you'll see a lot of additional data at an upcoming medical meeting. There's still, as you can imagine, a number of analyses that are going on that will look at a number of other endpoints in a lot more detail than what we're able to provide you with today.
What we can say is that overall, 93% of the patients remained on study in both A-LONG and B-LONG, and the results were comparable throughout the arms.
Okay. Thanks.
Your next question comes from Matt Roden from UBS. Your line is open.
Great. Thanks so much for taking the questions and congrats on the results here. So in terms of your individualized prophylaxis and weekly prophylaxis, both of those bleed rates are within industry standards. So can you help us with how that would be represented on the label? And then, Glenn.
Matt, this is Doug Williams. You're coming through with a lot of echo. We can't actually understand what your question is. You might want to go out of the call and come back into the queue again and see if you can pick up a better connection.
Okay. Will do. Thank you.
Your next question comes from Ravi Mehrotra from Credit Suisse. Your line is open.
Congratulations, Doug, on a great data set. Could you just walk us through and help us think how to think about the comment that you make with regards to the individualized prophylaxis arm, median dosing being three and a half days, but by the last three months of study, going to a mean of five days? Could you, for example, give us the median for the last three months for those 30% of patients?
Yeah, this is Glenn Pierce. I'm not sure your numbers are exactly correct. The median dosing in arm one was about three and a half days, and it didn't change much throughout the study, although patients had an interval where they could go from three to five days. So there were a proportion of patients whose PK-driven dosing did take them down to three days, and a proportion of patients, 30% in fact, whose PK dosing took them to a median of five days. And so we had a fairly narrow range to work with, but the bottom line is that with these dosing regimens, we were able to assure a very low annualized bleed rate. Does that answer your question?
I think so. Could I just maybe then squeeze another one in? Can you just remind us what your cutoff was for inhibitor formation? Were you looking for low-titer?
Yeah. So our cutoff is 0.6 Bethesda units, which is the standard cutoff that's used in hemophilia trials using the Nijmegen-modified Bethesda assay. And with those criteria, per FDA guidelines, we were allowed to see two inhibitors in 104 patients who had 50 exposure days, and we saw zero.
Your next question comes from Matt Roden from UBS. Your line is open.
Hey, thanks, guys, for getting me back in the queue. I didn't hear what the interim questions were, but what I wanted to ask is about the weekly prophylaxis and the individualized prophylaxis data. Both of those are within industry standards. So how would you expect that to be represented in the label? And then related, Glenn, how would you expect this to be looked at from a treatment guideline perspective and an adoption perspective? How would you expect the drug to be used?
Matt, thanks for coming back into the queue. We can hear you much better this time. I think it's premature to talk about what the label language might read. Obviously, that'll be a negotiation with the agency at the appropriate time and place. I mean, I'll simply say that I think the ABR data, the comparison between the on-demand arm and the individualized and the fixed duration dosing, obviously, the data is very positive in this particular study. So we're obviously hoping to have that reflected in the label at the appropriate time, but it's a little premature for that, I think.
Okay. Thanks for taking the questions.
Your next question comes from Ian Somaiya from Piper Jaffray. Your line is open.
Thanks for taking my question. Maybe just a follow-up to Matt's. Give us a sense of, from a market perspective, what portion of the market do you expect to adopt the weekly schedule versus one that you feel would probably require a three to five-day schedule?
It's premature to talk about market parameters and what proportions we expect. We developed the weekly prophylaxis arm, understanding that with Factor VIII Fc, or for that matter, any sort of Factor VIII technology, we wouldn't be able to get the majority of patients by PK to full protection for the week. We thought that this offered a viable alternative to individuals on on-demand or episodic dosing. So those two arms were randomized. We only enrolled patients who were on episodic dosing in those two arms, and we had a direct comparison with that very low annualized bleeding rate in arm two versus the usual or high annualized bleeding rate of 33 or so in arm three.
Your next question comes from Mark Schoenebaum from ISI Group. Your line is open.
Hey, guys. Hey, I was wondering if you could tell us it doesn't sound like you're going to release many more data details, so I won't ask that. But I guess the question is, when we take these bleeding rates that you guys have cited in the press release, and you went through in your prepared remarks, namely really the 1.6 in the individualized prophylaxis arm, can you actually define exactly how that was calculated, just to make sure we're clear? And then also, I noticed you guys had put up a slide historically at an analyst meeting where you showed historical bleeding rates in hemophilia A population. There are a bunch of dots, and they're kind of between the low single digits and the high single digits. But when you look at the ADVATE label, the ADVATE label actually says one as an annualized bleed rate.
So maybe, Glenn, I think you know where I'm going here, but can you help us interpret the 1.6? And can you give us an ADVATE benchmark that's comparable that you think is most relevant that we should focus on and why? Thanks.
Well, Mark, thanks for the question. It's probably not a good idea for me to get into a critique of our competitor. I will say that if you look at a variety of different clinical studies, including ADVATE, the annualized bleeding rates range from one to about 10 over the past 10 years or so. And so it's widely variable. And part of the reason for that isn't necessarily whether one product works better than another or not, but is due to the patient population, the design of the study, and other parameters that don't fully take into account the ability to compare directly between studies. So the bottom line is that one is looking for a low single-digit annualized bleeding rate if one is going to develop a prophylaxis regimen for patients who, in hemophilia A, have a bleeding rate of 30 to 40 a year.
The way in which we developed the annualized bleeding rates since patients were on study for largely between six and 12 months was to essentially look at the number of bleeds that the patients had while they were on study and annualize them. So if a patient had one bleed and was on study for six months, that's an annualized bleeding rate of two for that patient. It's probably just a little bit more complicated than that, statistically speaking, but that's how this kind of an analysis is done. Does that answer your question?
Your next question comes from Geoffrey Porges from Bernstein. Your line is open.
Thanks very much for taking the question. Could you just tell us a little bit more about the individualized prophylaxis arm? Was there a maximum extension or dosing that they were permitted? Could they go beyond the weekly dosing? And if they could, were there any population in that overall group that managed to get out to that sort of frequency? I know you mentioned the 30% that got to five days, but without giving us specific numbers, could you tell us whether there were some that trended out to the weekly? Thanks.
Yeah. Thanks for the question. So we're not going to go into that. We will look at frequency distributions as we analyze the data. The only frequency distribution we looked at was at five days to see that about a third of the patients were able to achieve five-day intervals. Arm one, the individualized prophylaxis arm, was designed to only look at intervals between three and five days. So although we'll have PK modeling that will demonstrate the proportion of patients that can go out beyond that as we go through the data, we hadn't actually put any patients on anything longer than five days in Arm one. We reserved that for Arm two, which was strictly a weekly dosing arm.
Great. Thanks very much.
Your next question comes from John Sonnier from William Blair. Your line is open.
Thanks for taking the question. Doug, now that you have the data in hand, do you see a profile that might actually lend itself nicely for the immune tolerance setting? And do you have plans to do any testing there? And I guess just to clean up on the safety side, I was glad we didn't see an SAE in this data set. I was curious, in B-LONG, when you adjudicated the obstructive uropathy, why couldn't you exclude the possibility that that was or wasn't drug-related? Thanks.
This is Glenn. I'll respond. So the ITI, immune tolerance therapy, as most of you know, requires frequent high-dose injections of Factor VIII over a period of six to 18 months in order to try to eliminate the inhibitor or the neutralizing antibody to the factor. As this program develops, we will look forward to utilizing the Factor VIII Fc in that kind of a setting, but it's premature to do it at this point. With regard to your second question on the obstructive uropathy, this is. I wouldn't say it's a common side effect in hemophilia, but it has been noted a number of times that obstructive uropathy can occur in the setting of hemophilia with replacement therapy. In individuals who have kidney disease for one reason or another, who may develop bleeding within the kidney, the bleeding needs to stop.
The bleeding is stopped by clotting whatever the leaking vessel is, and that can result in clot formation within the renal calyces as well as the ureters, and that's what constitutes obstructive uropathy. It occurs in normal individuals who may have kidney injury and is a cause of significant morbidity in individuals who do get kidney injury because these clots can be very painful and damage the kidneys, so in individuals with hemophilia, like normal individuals, they recommend a lot of fluid hydration to try to wash these clots out without them getting clogged up, essentially, within the renal tubules, but that can happen, and of course, if you restore an individual who's got a kidney problem to normal clotting, then you're going to see, in fact, clotting, and so I think that what we're seeing is the fact that the drug worked.
It was regarded as an SAE because it was a complication, and in fact, it was listed as possibly due to therapy, which makes complete actual medical and biological sense.
Your next question comes from Geoff Meacham from J.P. Morgan. Your line is open.
Hey, guys. Thanks for taking the question. Just have one on the filing here. I know for Europe, you're waiting on the Kids A-LONG study, but in the US or Europe, are there any other gating factors for the filing? What other work do you have to wrap up? And then a data question. I don't know if you can answer it, but obviously, the dosing interval and the bleeding rates are related, but can you give us any color on the time to resolve a bleeding episode among the arms? Thanks.
In terms of having the data necessary to file in the U.S., we have that now, both for factor VIII and factor IX. And the timing of that would be factor IX in the first quarter and factor VIII in the first half of next year. So we're in the process of putting together the BLAs for both of those molecules and anticipate filing on that schedule with the data we have.
With regard to your second question on resolution of bleeding, we were pleasantly surprised to see the responses in both B-LONG and A-LONG. B-LONG, 90% of the bleeds were controlled with a single injection. Nearly all of them were controlled with two. In A-LONG, I think it was about 97%, 98% of the bleeds actually were controlled with two injections. And so that demonstrates that the products are able to work rapidly and effectively. But probably what's more of a reflection of their ability to work rapidly and effectively is the response in major surgery. All 14 B-LONG surgeries were rated as good or excellent by the investigators, and all nine of the A-LONG surgeries were rated as excellent or good by the investigators. So that's the greatest stressor for demonstrating that a product can work in an acute setting, major surgery, that is.
Thank you.
Thanks.
Your next question comes from Joel Sendek from Stifel. Your line is open.
Hi. Thanks a lot. I was wondering if you can tell us what, for the AEs that are above 5%, what those percentages were or how high they go, and then if there's any material differences in those side effects between A-LONG and B-LONG that, comparing your press releases, it looks like you had influenza in one and not the other. If there's any other material differences between the two. Thanks.
No. The short answer is there aren't any material differences. The AEs, we haven't done all of the analysis, so we're not prepared to say exactly what percent each one had. We wanted to give you the top line and just indicate which ones were the most common. But these AEs, when you think about the fact that the studies ran over a period of a year, year and a half, they're typical AEs that not only would occur in the general population but would occur in the hemophilia population. So these AEs are not necessarily related to the study drug in any way.
Got it. Okay. Thank you.
Your next question comes from Thomas Wei from Jefferies. Your line is open.
Thanks. I just wanted to follow up on an earlier question. I thought that at the analyst meeting that you hosted, you had talked about the weekly prophylaxis arm in A-LONG and had specifically said that that was not likely to be a label-enabling arm of the study but more exploratory given the size of the patient population that was enrolled there. So I just wanted a reminder of how many patients did you have in each respective arm? And should I take your prior commentary from the call to mean that maybe there's a way now or you're changing your stance around that and there is a way to get this data into the label?
This is Glenn again. You should take the prior commentary as the fact that it was an arm in which we did not know what the outcome would be. We are pleasantly surprised to see that with weekly dosing, we can achieve a very low annualized bleeding rate in this arm.
Your next question comes from Marshall Urist from Morgan Stanley. Your line is open.
Yeah. Hey, guys. Congrats on the data from me as well. So just a two-part question from me. First, Glenn, could you talk about what the actual kind of physician behavior in the study was in terms of what kind of trough level did people end up redosing at and how far what was the average dose that was realized in the individual prophylaxis arm? To kind of talk about how much of what do you think this drug can actually do in the clinic was really showcased in the trial just in terms of the limitations that were on patients. And then second, related to that, just maybe I know the comparison was supposed to be between the on-demand and the weekly arm, but your thoughts on what we were seeing between the 3.6 and the 1.6.
Obviously, you're getting a lot of bang for your buck in terms of a single weekly dose. So what were the differences, you think, in terms of either the patients or how the two arms worked to get those so close in the weekly dosing arm? Thanks a lot.
Okay. So with regard to your first question, the trough levels that were specified in the protocol were in the 1%-3% range. And so we did do PK-directed dosing in arm one for the A-LONG study in order to make sure that the patients were in that range. If patients did have unacceptable bleeding, they were allowed to move up in their trough level. And so we didn't put any patient at risk. We made sure that they were sufficiently covered. And as you probably know, patients are heterogeneous. There are patients, for instance, those that may have pristine joints, such as younger individuals, who can easily accommodate a trough level of 1%.
There would be other patients, such as older patients who've got a lot of joint damage, who may not be able to tolerate a trough of 1% and may bleed at troughs above that. The study was designed to ensure the safety of all of the patient groups. We haven't released the average dose, and we'll release that in an upcoming medical meeting. The doses that arm one started at were 25 and 50, so a dose of 75 units per kilogram on a weekly basis. One might expect that that dose probably didn't vary too much. With regard to your second question, I think you've answered it. We were impressed with the bang for the buck, so to speak, that we got between the on-demand and the weekly arm. Those patients were randomized from an on-demand group.
And so the way the trial was designed, patients who had been on a prophylactic regimen were only allowed to enroll in arm one, which was the individualized interval prophylaxis arm. We wouldn't consider allowing a prophylaxis patient to enroll in an on-demand arm. And since we didn't know what the weekly arm would produce, that wouldn't be acceptable either. However, patients who were on-demand or used episodic therapy prior to the study were allowed to enroll in all three arms. And so we had a substantial number of patients who enrolled in arm one, the individualized prophylaxis arm, who had been on-demand or episodic patients. And then we randomized arms two and three only from episodic therapy patients. And so those groups were all very well balanced. We haven't gone into the details on the demographics. We'll do that in an upcoming meeting.
But we had sufficient numbers of patients from the perspective of all of the demographics that we got a good arrangement in those arms.
And Marshall, I'll just follow up by adding one last comment, which is, again, related to your bang for the buck comment. I think, as my prepared comment said, what we hope is that this data will encourage patients who are on episodic treatment now to consider weekly therapy with Factor VIII Fc. The annualized bleeding rates in that cohort of patients was, as Glenn said, a pleasant surprise. And I think really speaks to the fact that the drug provides good protection for those patients with that kind of schedule. So we think with a lower treatment burden like that, we really do offer a lot of bang for the buck in terms of the data that was presented.
We should emphasize, though, that we're not necessarily pointing out that a weekly prophylaxis arm is an ideal arm for all patients who are on prophylaxis. We know that from all of the PK work that came out of the phase one, two, as well as the phase three, that patients who have an average of a 19-hour half-life simply cannot make it to a week and still have protective levels of Factor VIII Fc. That's not possible.
Your next question comes from Eric Schmidt from Cowen and Company. Your line is open.
Good morning, and thanks for taking my question as well. Just about the hemophilia market, I think you've commented that you believe the factor IX market is worth about $1 billion and the factor VIII market currently about $5 billion. I was hoping you could map out for us Biogen's territories in terms of the share that you might have of each of those markets.
We're just not going to do that. You've characterized the market sizes. You folks know what the growth rates are in the market. You've developed your own models for how you think long-lasting factors are going to influence those markets. And I think it's probably best if we just leave it at that.
Just geographically, Glenn, you can't help us with what % of the market you currently own?
We don't own any. We don't have a market yet.
Assuming that we do get one with the products being approved. I mean, from a geographic perspective, Biogen Idec has essentially all of the world with the exception of Europe, Russia, the Middle East, and Northern Africa. I think in terms of dollars, it's probably about two-thirds of the market. That's kind of a rough calculation for you, but that's probably a good starting point.
Thanks. Very helpful, Doug.
Your next question comes from Yaron Werber from Citi. Your line is open.
Okay. Great. Thanks for taking my questions. Appreciate it. So I have kind of two main questions. One, can you give us a little bit of a sense? You said about 35% of the market now is in prophylaxis. So how much of it is an episodic? I mean, is it kind of the remaining 65%, or how is it splitting up between completely on-demand and some kind of something in the middle? And then secondly, I wanted to see, is there any way, based on your modeling, that you can, as you get to the market, you can help physicians understand who's going to ultimately be a good candidate for weekly therapy versus individualized treatment? And then final question, you said 30% of the patients can go to every five days in the individualized treatment arm. Give us a little bit of a sense.
What % then are getting therapy every two days? I'm just trying to get a sense of the outliers here.
Sure. Let me try to take those in order. So the rates of prophylaxis, they vary widely among age groups as well as among geographies. And so among adults in the United States, the estimate is somewhere in the 35% vicinity. One can look at the CDC data and try to parse that out with a little bit more rigor in terms of different categories. And so what that means is that if 35% are on prophylaxis, 65% are episodic. Now, in Northern Europe, the percentage of adults that are on prophylaxis is much higher. And then in each other geography, it varies considerably. As one moves into more of the developing world, there are far fewer individuals on prophylaxis. Among children in the developed world, the vast majority of children are on prophylactic therapy.
That's been recommended by the National Hemophilia Foundation's Medical and Scientific Advisory Council, as well as the World Federation of Hemophilia and other bodies. And so children in the developed world are generally all treated with prophylaxis. As they become teenagers and migrate into adulthood, that number tends to drop off a little bit, in part due to treatment burden, in part due to a variety of other things, including access to therapy. Now, when we talk about episodic therapy, it does mean that patients take the therapy in response to a bleeding episode. But in reality, if one looks at everyday life, if a patient knows that they're going to be doing something that's going to give them a very high chance of developing a bleeding episode, at least in the U.S. as well as in many parts of Europe, if they're not on prophylaxis, they'll take a dose.
And that's what's called intermittent prophylaxis. The amount of intermittent prophylaxis that's used is really not well described. But people are living their lives and managing their diseases accordingly. So I think that's all we can say regarding the 35/65 kind of a ratio. The candidates for weekly therapy would come primarily, we think, from an episodic therapy arm. And it offers an alternative to individuals who would like to have more coverage, but perhaps not the standard complete prophylactic coverage that would be enjoyed by the traditional therapy that's every other day or three times a week with these short-acting Factor VIII products based upon PK. With regard to the patients who got to five-day intervals, the 30% who got to five days, three days was the minimum in this study. So we didn't have any patients who were on two-day intervals.
The pharmacokinetics of a long-lasting factor VIII allow for the average 18-hour half-life. There's going to be heterogeneity in that mean, that average level. But the heterogeneity is such that it doesn't take it down to the equivalent of what short-acting factors are at.
Your next question comes from Rachel McMinn from Bank of America Merrill Lynch, your line is open.
Yeah. I don't know if this is really a great question, but I guess I'm just trying to better understand how these data would have compared to ADVATE if it were a head-to-head study, and I guess what you've been saying is that these patients were coming in from episodic therapy, so you don't really have that kind of background number, but I guess what I'm trying to understand is if you have 30% who are able to get to every five days, what would that look like if a patient's really tasked with facing the choice of, "Do I go to ADVATE or do I go to this product?" How many fewer injections are we really talking about based on these data? And then are there any plans to go to higher doses beyond 65 units? Would it make sense?
Would you be able to get more patients to weekly dosing if you went to higher doses? Thanks.
You're welcome. So with regard to ADVATE, we're simply not going to make comparisons. It's not appropriate to do comparisons between trials that had different demographics, different clinical trial designs, and that sort of thing. We'll leave it to you to do the math. If one looks at an average half-life increase of 50% between the Factor VIII Fc and the short-acting factors such as ADVATE, then you can do the math and figure out what that translates into on a yearly basis. With regard to the 30%, the second part of your question, I'm not quite sure I understood.
Your final question.
Go ahead. I'm sorry.
No. Rachel, what I would just say is that where we did see a direct comparison with ADVATE was in the PK extension. And consistent with what we saw in the phase one, two results, we saw about a 1.5-fold increment in the half-life. That is the one direct comparison you can look at. As Glenn said, you can do the math, make the calculations. I alluded to them in my prepared comments. Again, it does offer, I think, a significant reduction in the treatment burden for patients receiving factor VIII, the short-acting versions of factor VIII.
Your final question for the day comes from Marko Kozul from Leerink Swann. Your line is open.
New question. With the advent of newer innovative therapies, the World Federation of Hemophilia seems to be advocating a new higher goal of titration to 15% plasma factor for patients. So I was hoping maybe you could talk to us a little bit about how you see the hemophilia market developing or expanding. Thanks.
Thanks for that question. You're right. At the July World Federation of Hemophilia meeting, Mark Skinner, who was the president of the World Federation, talked about a future in which patients would have higher trough levels and more protection from bleeding so that they could lead even more normal lives rather than going down to very low trough levels and needing to be careful when they were at those very low levels. I think that the development of long-lasting factors is the first small step toward a goal like that. That goal has really been unachievable given the short half-lives of the existing factors, especially with regard to factor VIII. In order to maintain high troughs, one would need to take the factor VIII literally every day, which is doable but is an incredible treatment burden.
And so as this whole field progresses scientifically, moving to this first step with this first generation of long-lasting factors is a step in that direction. It offers patients the potential to either decrease their treatment burden or to increase their protection levels as their individual situations may dictate, or some combination of both, which is probably what the practical reality of it will mean. And then future scientific work should be designed toward developing even better products than the current ones.
Thank you, everyone, for joining us today on the conference call. This concludes our call. You may now disconnect.