Maxim Jacobs
7 February 2017

Edison KOL call


The fourth in our KOL series, Edison sponsors an interview between Dr. Jaroslaw Maciejewski, Chairman of the Department of Translational Hematology and Oncology Research at the Cleveland Clinic.  The conversation featured a discussion on current and emerging PNH treatments. 


Call Leader: Okay, great. Thank you Doctor for taking the time out of your schedule to be on the call today. I was just wondering, maybe you could start by describing your practice?
Doctor: We are a coordinated referral center, big volume, big hospital. I come from the background of NIH whereas NIH was a big referral center for a sort of second opinion and also a lot of indigent people, people from other countries. My hospital is more in the trenches of a real live health delivery, but because we are 27 hematologists as a volume, if you wish, and the area we cover is much bigger. This is not my source of patients, it’s just by word of mouth. Because I see so many patients they have all this on website, online chat cabinets of PNH patients. I see a lot of consult from far away, from places like Florida, California, New York and so on. These are usually consults with recommendation, rather than local patients who are being managed by us by daily basis.
Call Leader: Great. How many patients with PNH do you have and how many of those are on Soliris right now?
Doctor: Okay. What I have is chewy because if I have a patient who we recommend it to, and start it on Soliris and the patient is in Traverse City, Michigan and I see this patient three times a year, do I have this patient? I would concede that I have this patient. They are patient whom I really have by being a primary healthcare deliverer, if you wish, with resource that I am an expert supporting a local hematologist in important decisions. So, among those we have 29, I believe, currently patients on eculizumab. I see since 2002 our database it’s like 180 patients, but many of those patients have smaller clone and might not be necessarily classified as PNH. If you go to a sort of hard core PNH with large clone, it’s a typical hemolytic PNH, his number is going to be around, since 2002 around 80 and currently I have probably like 40 patients.
Call Leader: Great. That was very helpful. Maybe you can just explain also what’s the underlying mechanism of Soliris in preventing thrombotic events in PNH patients?
Doctor: In preventing thrombosis?
Call Leader: Yeah.
Doctor: Prevention in hemolysis?
Call Leader: Yeah, hemolysis.
Doctor: It was a question already on the original trial if PNH cells actually are thrombogenic or whether it’s a hemolysis that is prothrombogenic. The trial showed that by decreasing the hemolysis, of course the number of cells that carry PNH phenotype increases, the overall risk of thrombosis decreases. It was sort of proven to me that the propensity to thrombosis is related to the process of hemolysis. Right? Of course process hemolysis is related to the size of PNH clones. The more PNH cells [divide inaudible 00:06:25] the more hemolysis you have and stuff. By itself, complement cascade starting good classical automate activation pathway goes via C3 and eventually via some other steps, hits C3 and C3 undergoes activation and some [inaudible 00:06:49] cleavage and forms membrane at that complex, which causes susceptible cells to die from the influx of water by osmotic means. White cells, unlike red cells, are protected by additional mechanist from it and normally normal cells are protected from action of complement by having CD55 and CD59 on the fourth phase, which essentially counterbalance activation at the C3 and C5 level.
Call Leader: Mm-hmm (affirmative). Do you think if there was a drug that was targeting C3, do you see advantages to that?
Doctor: It makes sense to target the complement cascade at the earlier stage. The big question in the room is whether there are some inputs into C5 rather than via C3 that could activate C5 directly without C3? Theoretically speaking, one could easily conclude that the C3 activation is indeed proximal and therefore will prevent C5 activation.
Call Leader: Mm-hmm (affirmative). Do you think like a factor D inhibitor would also have kind of the same potential issues as a C3?
Doctor: Factor D would be just even earlier than this. The question would be whether both was factor D classical and alternate complement activation [inaudible 00:08:50] would be both inhibited?
Call Leader: Okay great. Just go into your, the general population PNH, just based on your experience, like what percent of patients are refractory to Soliris?
Doctor: Usually it’s a gray zone because it depends on the definition of refractory. If we stringently define refractory patients who are transfusion dependent and remain transfusion dependent, versus patients who did not experience sufficient elevation of hemoglobin, or whether these are patients and it of course depends on the input. The input would be if I have transfusion independent patient with hemoglobin is eight, I mean this patient cannot be made transfusion independent, he is already transfusion independent. However, the most dramatic example would be a patient who receives transfusions, gets on Soliris and still has a need for occasional transfusion. Or whose rising hemoglobin is inadequate to what we would expect. If we are less stringent, probably 10 to 15% of patients might have values decrease of incomplete response ranging from the refractoriness to a sort of insufficient response or less than perfect response.
Call Leader: Would you consider that 10 to 15% to really also include not just the refractory but the suboptimally treated?
Doctor: Yeah.
Call Leader: Okay.
Doctor: Maybe it would go then if you are not as stringent and it’s to 20%.
Call Leader: Okay. Great. In terms of kind of the mechanism for either the suboptimal treatment or being refractory, is there like a mechanism for that or is there maybe another underlying disorder that’s causing it?
Doctor: I mean essentially you can [inaudible 00:11:25] three different possibilities that I can think of easily, there are probably more. One would be that anemia is not completely a function of hemolysis but a function of the breast production. These with the patients who have low reticulocyte count and whose hemoglobin level depend on both the production and extraction. Second, patient has adequate production, however, it’s under those so he is susceptible to break through hemolysis or either episodic or at the end of each treatment cycle with an endogenous level of Soliris are the lowest.
Finally, the third possibility has been involved as an extravascular hemolysis, which is related to opsonization of erythrocytes with C3 and phagocytosis of opsonized red cells by retical endothelial system in the liver and spleen. As such, this process is not associated necessarily with elevated LDH and is C5 independent. If you wish, this can happen in a fraction of patients. Normally the C3 mediated the extraction of red cells has very little physiologic significance due to the circumstance that this process is much slower than pushing through the cascade of and formation of membrane at that complex. In the situation that there is no inhibition of C5, C5 kills the cell by much faster mechanism and they can accumulate and become targets for phagocytosis via a complement receptor two.
Call Leader: What percentage of your patients would you say discontinue Soliris in any given year and generally what’s the reason for that?
Doctor: Very few. Bone marrow transplant would be one. I stopped Soliris in a couple of patients who were inappropriately started, as they did not have really PNH or the PNH was so minuscule that it was crazy to administer this expensive drug. Yeah. These are these two major. Finally, I had in the last 20 years two patients, one and a half, but two patients whose clone disappeared and was not any longer detectable so that the continuation of Soliris was not justified.
Call Leader: That’s interesting. The route of administration of Soliris, being an IV, has that proven to be a difficult burden for patients?
Doctor: I mean, different scenarios. One scenario is of course that the patient lives across of the hospital and can come over, do that and it’s not a major disruption of life. Verus other patient who have to drive 150 miles every two weeks or 200 miles every two weeks, it just makes it more difficult in terms of by itself administration, it’s a very good drug, but this is a caveat that one is bound to follow calendar and sort of plan ahead with many of the travel, ideas that people who have.
Call Leader: What percentage of your patients do [crosstalk 00:16:16] for another route?
Doctor: For example, patient go on vacation and then you have to sort of dance around how to schedule it that the infusion does not come middle this vacation because they are away. Conversely, the patient that’s across of clinic or patient has to drive for two hours to the clinic.
Call Leader: What percentage of patients do you think would prefer to have another route of administration like subq or even oral?
Doctor: It depends how often is subq. Oral is no brainer, it would be hard to believe that there is anybody who has access to an oral drug would not want oral. Subq might be tricky depending of the volume injected, the frequency injected. Do you have to inject it twice a day, once a day, twice a week? Of course, you measure it against benchmark of every two weeks IV infusion over half an hour versus a benchmark of every two months infusion over whatever, four hours. These would be changes in the demographics of patients who have something wrong “with complement.”
Call Leader: Do you think every four hours every two months, is that preferable to once every couple of weeks for a half an hour?
Doctor: To do what?
Call Leader: Just in terms of convenience for the patients, assuming they’re not 200 miles away from the clinic. Like let’s say they can go, it’s a relatively local clinic that they get the infusion. Do you think there’ll be a lot of people who prefer like a four hour infusion every eight weeks to once every two weeks for thirty minutes?
Doctor: I mean, forget that majority of the patients with private insurance will get it at home by home health nurse. So this is another factor. Overall, it’s difficult to compare weekly subq injection to big infusion every four weeks and it might not necessarily be safe or work. In the end of the day we need to measure the frequency, you know the one that is more efficacious. It’s comparison issue to what would be identically available. If you compare this to a pill versus compare it to injection, versus compare I have to go to the clinic every two weeks it’s two hours drive, versus I have a friendly and pretty home health nurse coming with whom I have a nice discussion, drink coffee and she infuses it to me every two weeks. There’s a spectrum of sort of circumstances.
Call Leader: Sure. Would some of these competitor products have to be actually superior to Soliris in order for you to switch if you’re not considering convenience?
Doctor: I’m sorry, I lost train of thought.
Call Leader: Sure.
Doctor: Somebody was in my room. Can you repeat the question?
Call Leader: Yeah, sure. A lot of doctors don’t like to switch patients from drugs unless there’s a reason. Would some of these competitors have to actually have better efficacy than Soliris for you to consider switching to them?
Doctor: Again, are they single agent or do they have to give a companion with Soliris? Are the correct response achieved with Soliris or isn’t? If correct responses achieved with Soliris and there is some sort of habit issue versus switching to new, this new should be at least good or have some convenience factor to it, doing it every two months or being able to self administer or this type of thing. I think one has to see it in the context how the patient is doing on the current drug.
Call Leader: Just going back to kind of the convenience issue, if someone that had a subcutaneous version, do you think a two times a day version would be viable?
Doctor: Hard to say. Clearly when I indicate it to some patients who have a very well established home health delivery system by a nurse, these patients say, “Well, I have this lady. I always nice chat, she’s ... She comes on the weekend and doesn’t bother me and then I don’t want to deal with this every day, think about it,” and so on. If this is a pen like an insulin pen, which takes two seconds to administer and it just you know, you just without interrupting a major [inaudible 00:22:17] versus it’s some sort of a pump device, which the volume is big. This would clearly influence whether twice a day is doable.
Call Leader: That’s very helpful.
Doctor: The level of desperation is also different. Somebody is already on a drug that was $800,000 a year and still needs transfusion and accumulates iron, and can a drug that is twice a week but it would really absolutely convert them into responders. This might be a different issue than somebody who’s doing very well currently on Soliris and you say, “Hey, I can switch you to something else.”
Call Leader: Mm-hmm (affirmative). Do you think there would be a market for combination therapy with Soliris?
Doctor: It remains to be explored. It’s clearly the original design of clinical trials is such that it’s easier to combine it and say, “Hey, I’m going to treat refractory patients, now the patients without adequate response with my agent.” Rather than say, “Hey I have here a 100% effective regimen.” So this will play a role, you know where the patients are. Now if patient has C3 mediated hemolysis and the drug in question is another C5 inhibitors, how will this person would be helped? Right? And visa versa, how the patient would help if you have two very effective drugs that work via C3. I hope that this answers the question.
Call Leader: Yeah. That’s very helpful. I just wanted to ask some questions. Given what happened with Alexion a couple of months ago with the sales practices being put into question, I was just wondering on a scale of 1 to 10 with 10 being the best, like how do your fellow like PNH treating physicians perceive Alexion as a company? Are generally people really happy with them? Are there some that really love them, some hate them?
Doctor: Them being?
Call Leader: Alexion.
Doctor: I think Alexion is a very well company that does everything that they have to do to succeed. They don’t nickel and dime stuff that is needed for marketing serving, such that is that some of their projects might be considered too aggressive. I clearly, I often see patients who have 1% of clone where I am stopping eculizumab because the patient never had the PNH to begin with.
Call Leader: Is that because of the sales practices you think or just aggressive marketing? Hello? Hello Doctor?
Slingshot Admin: Hey Max. I’m not sure if we lost him there Max. I can redial but I think he hit mute.
Doctor: No, no, no. Here, here, here.
Call Leader: Okay.
Doctor: I’m being disrupted because I’m running clinical service. Can you repeat the last question please?
Call Leader: Yeah, sure. The people who are being treated, if they have like 1% of clone, is it because of aggressive marketing practices by the company or sales practices?
Doctor: I think it depends on who is the prescriber or if you see somebody who is an oncologist and see breast cancer and from time to time lymphoma, and they have a patient with unclear anemia, they found that the clone is 1%, they are more likely to prescribe it. I would be by far less swayed. In some countries there are clearly guidelines, and the age has to be two and a half, the PNH clone has to be at least 20% and there has to be some alleviating circumstances.
I call them, when I do the speil to the patients that, “Listen, for your treatment, since you are not transfusion dependent, to start you on it, you would have to have the certain pros and cons and the pros as to advantage. The cons is of course the inconvenience, being bound to it, and stuff. The cons is also the fact that your hemoglobin is relatively good so we are improving hemoglobin of 10 to 11. But the pros would be of course the fact that you alleviate the risk of thrombotic complication, which is greater in patient who already had the thrombotic complication versus patients who didn’t and never have [inaudible 00:27:44]. It’s greater your patient has elevated D-dimer versus patients who don’t have elevated D-dimer, the benefit is better in patients who have more severe anemia or are transfusion dependent versus those who aren’t. Or who have more constitutional symptoms including fatigue and other, chest pains, pain swallowing, et cetera.”
Having said that, of course many of these symptoms would be before [inaudible 00:28:10] patient who have 1% clone. So these are these patients that if I would get, I see that recently had the patient like this and I see the patient is 1% clone, we’ll start it on eculizumab. His blood get crazy to continue eculizumab. If you have only 1% of white cells and .1% of red cells, what is their contribution to hemolysis? The white provide you a sort of ceiling, so you know if a patient has certain, let’s say 50% of white cells and 10% of red cells, then steady state hemolysis is such that it destroys 40% of cells from 50 to 10 of red cells. If the patient has only 5% of white cells and 1% of red cells, you know that the steady state distraction is sort of, say, 4% of cells. Now if I block this, the hematocrit would go by 4%. See what I mean?
Call Leader: Yeah.
Doctor: Now, how quick it would go up depends also on the reticulocyte count. If patient reticulocyte count is low then his anemia is more determined by the lack of productions and lack then increase extraction. If I have somebody who is 10% clone but 1% of retics how is going to help him that I block eculizumab he is not making? Right?
Call Leader: Yeah.
Doctor: These are these thoughts that one has. Having said that, I probably stopped one or two patients in the last 10 years who came like really with tiny clone and I’m like, “Why are you getting this drug?” I am more likely to do it because I have a certain confidence because I see so many patients versus nobody wants to have the liability when you have an FDA proof, the test comes in, PNH positive, nobody reads the fine print that this is only 1% clone and the patient ends up on eculizumab. I have seen these type of scenarios.
Call Leader: Just going to reimbursements, how hard is it to get reimbursement for Soliris and has it gotten easier or harder in the last year or two?
Doctor: I have no reason to assume that it will get worse. The reimbursement, what I do is I ask patient to call Source One Pharmacy, or whatever it’s called. There are a bunch of case workers who are sort of pushing this whole process through. At certain points they might need a progress report with my description that this needs to be given, this is being, you know, then sent to insurance company. This one sort of pharmacy is essentially a bunch of nurses who do nothing else but extort the permissions from industry. This good, this helps a lot. So it’s much easier for them for many other drug.
On the other hand, sometimes people get approved by the insurance but end up with a huge copay like $5,000 or something like this. This is in subject to various measures how can we alleviate it? I don’t recall the moment that the company said, “Yeah, I’m just going to eat this cost.” Sometimes they address some foundation, rare disease foundation has some fund to support deductible payments for rare drugs for rare diseases. At the end of the day, I think, I cannot recall anybody in the last whatever, 15 years that the drug was on the market, that I couldn’t give it. There was always some way found that the patient gets it. Now, it might be not entire true, we are very fancy private clinic, I have across the board better approval rate with insurance having this certain gravitas than maybe other places. It could be that the rejection it would be higher if somebody has a higher practice that specializes with breast and colon cancer.
Call Leader: Mm-hmm (affirmative). That’s very helpful.
Doctor: Then you [crosstalk 00:32:43] push less, you know.
Call Leader: Great. No, that’s very helpful. Just going to the pipeline, I’m sure this is tough just because there isn’t that much data, but which of the pipeline products do you find most exciting?
Doctor: Everybody says that at the end of the day, I think two oral drugs that I know of being developed would be the home run assuming that they don’t cost anybody’s liver to explode or some other horrible side effect. The C3 line has of course a burden to overcome is that while we know that the blockage of C5 over the extended period of time does not increase in some unreasonable risk of infection, it’s not clear that one could extrapolate the same things from C5 inhibition. I would contend that probably is going to be the same, but it’s not that easy to conclude it without having actually data. Inhibition of C3 is less valid so it might have harder time getting through clinical trials. Rather than in other C5 inhibitors, let’s say I have much better subq form of C5 inhibitors, long lasting acting C5 inhibitor, I think the issue of complication of long term inhibition with antibody C5 will be much easier to explain as saying you know I have the same toxicity profile as an antibody or something like this. These are the factors that would play significant role in this.
Call Leader: Okay. You mentioned the liver tox. How concerned are you by the liver tox that we saw in the ACH-4471?
Doctor: You mean the Achillion?
Call Leader: Yes.
Doctor: It’s always concerning, but I was told that this is not deadly to the drug. I was told that the drug is not going to be signed by it.
Call Leader: Mm-hmm (affirmative). Okay great.
Doctor: Dealing with liver toxicity is tricky, particularly in patients [inaudible 00:35:29] overload and so on, so it has to be really attributed. I think that always a question can come up in post marketing period. Now, if there is another C5 agent, let’s say oral or subq, it would clearly be helpful, but those who don’t respond to regular C5Q why would they respond to the other C5Q? You still need some sort of less stringent agent, and maybe money here. Yeah. I was thinking that whether or not one has to also measure one drug versus what’s coming on. In other words, if you have Soliris that is currently available, it’s difficult to say, “Hey I have this other drug that is ready to compete with this.”
This other drug might compete actually not with Soliris but the next generation Soliris. This is somehow dynamic process. I don’t know that it’s early enough to say that the toxicity of this Achillion drug was such that it’s going to be a death of the product. Anything that is not C5 inhibitor has to go through testing in terms of the, also increase propensity to infections because the extrapolation might not be correct. The C3 inhibition might be much wider range and therefore produce more complication or not. I don’t know that this is something that can be deduced without experimentation.
Call Leader: That’s extremely helpful. What do you think about Akari’s drug that’s developed from tick saliva?
Doctor: In my opinion the biggest advantage of the drug is the entry to a market via a sort of niche. Otherwise, let’s face it, you have a drug A and now you say my drug, I want to administer [inaudible 00:37:59] setting. Many people would say, investigator European countries or whatever I heard it all the time say, “I have already effective drug so how can I justify it to start the patient on drug B when this drug was not tested yet?” Versus then you have to result to a sort of I have the refractoriness to currently available standard care and therefore I can use the drug B, but then you narrow the number of patients “available.” Finally, you say, “Hey, this patient could be on Soliris if it were not this expensive, but if I had something cheaper I would put him on it but he is not necessary benefiting from life saving action of Soliris.”
I think I would divide this concept of how do I get on the market another drug or how is it needed by two things. Is this drug being able to be tested successfully? Then, let’s say assuming that it’s FDA approved, whether it would be used. If alternative drug to Soliris is twice as expensive to Soliris, then the insurance company might say, “Well, only if you for Soliris you can do the twice more expensive drug,” for instance, and so on. Getting there, it might be difficult to begin with. Again, if you look only for refractory patients, 10% let’s say for refractory patient with Soliris, the other who didn’t get Soliris are not severe enough so the outcome will be less well defined. Right? If outcome is death, who is dying from PNH? No one. You would take for 20 years to get the outcome like this.
So you have to have a surrogate outcome and keep it compliant by laboratory means, the rise in hemoglobin or whatever. This is the type of thing that you can test and then extrapolate what would be the benefit of giving it. If the patient is refractory C5 for my experimental drug is C5. Now the spit drug, the saliva or whatever, complement inhibitor drug, I think has a big advantage that if they find enough patient with this polymorphic that these patients are totally refractory to Soliris, they wouldn’t have to go through this ethical dilemma of yeah, I’m withdrawing the patient, the drug that is FDA approved. On the other hand, how often it has to be given and the subq drug, like they call, so efficacy issue has to be proven as well.
Call Leader: Are you concerned at all by the immunogenicity issue, or potential immunogenicity issue? Yeah.
Doctor: Yeah, no. I think that the consternation is more than let’s say in another 100% [humalized inaudible 00:41:09] molecule. Yeah. That is some sort of a more of a concern. Again, I don’t know that this is a killer to the drug or whether this will be something that’s going to be overcome.
Call Leader: Okay. Great. Just kind of to wrap up the call, if you had like a crystal ball, in five years let’s assume that some of these pipeline products have made it on the market and there might be a biosimilar Soliris out there, what percentage of the market do you think Alexion will have retained?
Doctor: If they have the long lasting drug, this might be a choice for many patients here and dealing with subq every day. I get it every two months, I don’t have to remember, I don’t have to, it’s much easier to schedule vacation around something that is every two months. I think you have to see the Soliris might not be the only thing you are running against. If let’s say the longer acting agent or the more convenient agent is priced out of equation, it might be mandated by insurance company to use this and the other will be for authorization when you fail the other stuff. There are all these caveats in the practical application, I think, that it’s difficult to sort of envision it once. I got my bullet points why this might be an issue at an institution like ours.
Call Leader: If you could put, I don’t know, just some sort of percentage, do you think they’ll be able to keep 70% of the market or do you think it’ll be like 30? Just a wild guess would be fine.
Doctor: If RA pharmaceutical comes up with an oral agent that looks completely complement and has no side effects they are going to retain zero market share. I think it depends a little bit. There will be always a niche for the patients who don’t have optimal response, a niche for patient who are not pleased that they have to drive for 200 miles to get the infusion. Currently medicare does not cover the home health. Most of the private insurance want home health because it’s cheaper than markup in the hospital. Medicare is more difficult to deal with because they don’t allow to increase the dose but you have to decrease the interval usually, maybe it depends on the state, and then the [inaudible 00:44:05]. This is the one of the important issues to remember. That patients who get Medicare usually are not eligible for home health care.
If they don’t home health they don’t have the convenience and private nurse, they have to be mobilized in order to receive the benefit. Here you have a dude who work with patient, we feel he has PNH and this guy is being started and there is three different drugs on the market. Versus, this is a guy that Soliris is still on the market and everything is something that needs to be authorized, and it’s more expensive. Or he did not respond to Soliris in which case if we have on the market another C5 inhibitor how exciting it would be? It would be not exciting at all. There is a little bit reciprocity issue here. It would be here to conceptualize that the doctor who is ... That the patient who is receiving it is the patient who has some convenient gain from it. Otherwise, what’s the point?
Call Leader: What percentage of your patients would you say are on Medicare?
Doctor: Probably 20%.
Call Leader: Okay. Great. Thank you. That was all very helpful.
Doctor: If you live close to the VA hospital you have more people. Again, there is again the bragging number to this escapades, you check whatever, if they have the website, but if you would check that they took it or whatever some other company that has a subsidy of a company that it’s different. I think many of the factors that have to be considered are a little bit unknown at the moment because it’s a little bit fluid with regard to the indication. I think going for the indication and refractoriness is easier at the beginning because there is a true medical need versus replacing.
Then, if you have another C5 you can benefit from the fact of the long term toxicity and the complication profile is known. Obviously, if somebody has a very good response to Soliris what would be the point to switch him to another drug that is every two weeks? That’s why there’s biosimilar, unless it is a gigantic financial bad gradient, it would be sort of big no-no to me. Why I’m going to mess around with another drug if it’s not much cheaper or more convenient to administer or less frequent also?
Call Leader: That makes a lot of sense. It was very helpful. Thank you so much for your time. I thought this was a very useful call for me.
Doctor: No, no, absolutely. This is such an explosion now of these companies that feel that there is ... Coincidentally I know at least about the actual chemistry of this drug from whatever spit from the saliva. Right? Of whatever, the one that you mentioned. This might be actually the best drug, for all I know. It’s just currently the advantage is that it would be easy without major deal to get the drug for patient use if I found the patient who has this polymorphous and is not going to respond to eculizumab. So this is their entry. Obviously, they are not going to survive selling drugs to patient refractory to eculizumab based on some genetic polymorphous.
I think the strategy is to show in couple of these patients that it’s safe and then go ahead and stuff. Similar in drugs that are given common to eculizumab. If this is a C3 drug, you have good result along with C5 and you have competitive or you have well thought [inaudible 00:48:43] studies in terms of the activity of C5, you can show that okay, I started the patient as a second agent but I am going to now after three months withdraw the eculizumab. I think it’s just the first step is to add it and see how you do, and then the second step would be withdraw.
Call Leader: Great. Yeah, no, that definitely makes sense. So thank you again for all of your insight, this has been extremely helpful. Yeah.
Doctor: I mean you guys incredible due diligence on these things, I am always very impressed because it’s like you know so much about this stuff. I think price issue will play a role. In Europe or in Australia you have all these committees that approve the drug or you have the centers that the patient has to be seen in order to treated with the drug, which it’s much easier. Versus here you get this sort of, you know it’s a freestyle. Somebody who is an oncologist in the field he has one patient with PNH with 1% clone, he puts him on the drug. This patient would be not necessarily a candidate for any other drug but for Soliris particular [inaudible 00:50:06].
I mean, the easier administration as in less stringent would be the indication. If I have to go through all this coo-coo plow for proving, planning and patient has to come every two weeks, potentially might need the port, it’s different. If I have a patient with aplastic anemia and 10% clone and I say, “Hey, I’m going to put you on ATG,” and then once ATG is given I cyclosporine because you have a small clone I’m going to add that, an inhibitor because it’s just another pill, it would be different. Then I have a fancy shmancy drug that costs $10,000 every infusion, how can you justify to give it to somebody who has 4% clone?
Call Leader: Mm-hmm (affirmative). That [crosstalk 00:50:51].
Doctor: The liability behind it is that it’s easier to put everybody, how the label is written, anybody on eculizumab [inaudible 00:50:59] that you might have because you felt had a patient with PNH but was relatively asymptomatic. Now the patient comes with a blood clot and you feel horrible.
Call Leader: Mm-hmm (affirmative). Is there also a little bit of a profit motive as well? I know a lot of these people get home health, but since you can get reimbursement through the infusion, is that pushing people to the prescribe it as well?
Doctor: You know, many private practice, to be honest with you, many private practice don’t like to give it because the reimbursement is very low and they have to foot out upfront a huge cost. They don’t get it for say, let’s say if you have Medicare patient whom you treat with eculizumab, they pay like six months later. Meanwhile, you have to purchase $50,000 worth of drug every month and you get paid in three months, maybe. For an institution like ours, they have probably huge supply of eculizumab all the time. I know it because sometimes I have a patient from outside who travels on the day that he’s due, so we say I’m going to see you in the clinic and I am going to infuse the drug for you, no problem. A private physician might not have, you cannot afford to stock it.
Call Leader: I can understand why they wouldn’t want to do that. Yeah.
Doctor: If a private practice doctors who yes, they would make a big overhead, markup let’s say 100%, then they don’t get paid for three months. They have to buy or foot out $100,000, very difficult to balance book this way. I got a lot of patients that we got and they come to infusion centers just simply because private doctors just doesn’t want to deal with infusion of this drug. It’s a profit motivation.
Call Leader: Yeah. There’s a lot of risk I guess for the private practices.
Doctor: Unless somebody has a huge volume, you know, whatever, Cancer Centers of America or whatever they have. Every five minutes they are on TV, so maybe they have enough patients. I see a lot of patients, we have like tons. Remember, it’s a big hospital so there is a vascular service, atypical aHus and so on. It’s much easier for us to circumnavigate it.
Call Leader: Yeah. No, no, that makes sense. Great.
Doctor: [inaudible 00:53:37] is also impossible because the DRG is so that if you get reimbursed for the total cost of visit and you have a drug that is $18,000 you never break even. You know?
Call Leader: Wait, so the DRG for which procedure?
Doctor: For eculizumab in house. Let’s say patient [crosstalk 00:53:59]. I mean, how many time patient was discharged, rode in to me and I gave it to an outpatient basis because otherwise the DRD it would be like it’s a big lawsuit the hospital. Right?
Call Leader: I wasn’t aware of that at all.
Doctor: You know this is not like these patients are frequently admitted but whenever they are, they prefer to sort of throw patient to the hospital, discharge him, get the infusion and admit him for whatever his patient is in hospitals and giving it in hospital. It would have to be like ICU or something.
Call Leader: Mm-hmm (affirmative). Yeah, I understand. That’s probably relatively rare, I would think.
Doctor: No, this is not common, but it does happen from time to time. I borrow a lot of drugs, so I have a patient coming in three days for, but I have a patient first time visit and patient needs to, this is today his dose. I say, “Can I borrow from this patient?” Meanwhile, Alexion ships a new drug. Alexion is excellent in terms of this mumbo jumbo approval and so on. I think I want to say that anybody who needs the drug really will always get it. The only issue is if there is big copay who is going to pay the copay? My feeling would be Alexion should be paying the copay, if patient cannot afford it. Usually what is they reach out to some disease foundation or some other stuff.
Call Leader: Mm-hmm (affirmative). I’m glad it ends up usually getting fixed in the end.
Doctor: Yeah, somehow, somehow. I think there is so much profit margin on people who get it and insurance pays it, the few patients who have problem getting insurance, they should be taken care of by Alexion, but that’s my opinion.
Call Leader: Mm-hmm (affirmative).
Doctor: Maybe some legal stuff, if you have to reimburse equally everybody per, across the board, you cannot just make exception. For this guy insurance paid $10,000 out of $18,000 drug so we are going to ease the price, versus the other we could have charged 18,000. I think there are some legal burden to this, doing it this way.
Call Leader: Yeah. It’s just a complete mess.
Doctor: Yeah. Yeah, yeah, yeah.
Call Leader: So thank you again for your time. This was very, very helpful.
Doctor: Absolutely.
Call Leader: Have a great day.
Doctor: Yeah, you’re welcome. Bye bye.
Call Leader: Great. Thank you. Yup, bye.


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