Elan at SG Cowen AnnualHealthcare Conference
QUESTION AND ANSWER SECTION
<A>: I will answer the second part and then Lars can do the first part. The second, first of all with regard to patient information, we are in a very – oh, I will repeat the questions, same question or different question. Two-part question, one is compare both patients, any similarities, commonalities and the second patient any further comments on that. So, let me preface these comments by saying something, we are – this is a very unusual situation we are actually discussing patients in
the public arena, this would not be held under any other circumstance that we know of, how these discussion would be occurring. They would normally be occurring between Biogen and ourselves, the FDA and the investigators. So, because of where we are and because of the very uniqueness of this, we can comment on first two patients, but just as a going forward process, we are not going to comment on all of the other patients as we go through this process. It would not be a prudent
thing to do and potentially very misleading to these various constituents that I just went through.
And not in a way that would allow us to do a methodical prudent review of the patients.
So, patient number two, what I can tell you is as follows. The patient is no longer in the hospital; patient has been checked out and is in rehab center. The patient is showing some signs of improvement. When I was told that, I asked the questions, since I know, I doubt anyone else in this
room understood PML two and a half weeks ago. My question then was, I though, PML was a 100% fatal disease or situation and the response is that's not always the case. So, patient number two has checked out of the hospital, number one, in a rehab center; number two is showing some
signs of improvement; number three and was taken off drug in December. Commonality of the patients, if you will ask Dr. Ekman, I can answer some of them, why don’t Lars, you take that?
<A>: It is very difficult without going into the details of these patients. And, we have, how do we not do that. One commonality is that neither case was clear-cut, specifically to the first case, there was a big controversy regarding when the diagnosis was made, what was the right diagnosis, et cetera., it is very clear that from the signs and the symptoms the PML related symptoms started much, much earlier than when the diagnosis was made. The other case which, as Kelly mentioned, got this diagnose much faster, and the prudent action was not taken. I don’t want to go into the specific cases, one of the cases that’s also in the public demand had a malignancy, had an malignancy for which it was treated. That, that, I cannot be more specific without revealing too much of the patients and we should not do that in public domain. Yes next question.
<A>: Yeah. Second patient.
<A>: No, I am just going into the facts.
<A>: I don't know, that's here, which I am sure you might try to see who that is. But, I know, – we know he was taken off drug in December. Yes, all the way back.
<A>: The question is, from a production point of view as and when Tysabri is back on the market available, where we have enough supply. Well, I can you that Jim Marven and myself, up until the middle of February spent the last 3 or 4 months on supply. Of course, we are looking at the demand curves – Biogen has two plans that are operating today. One in RTP, one in California, the RTP plant is producing Tysabri. As we speak and we will continue to produce Tysabri, as we speak and in addition to that, this pause actually gives us an ability to continue along with some of the engineering work that we are doing in both North Carolina and California. So, that as we need it, that the yield from those plants actually can be up and perhaps quite significantly. So, we continue to manage the supply side, obviously, we have to fix now this regulatory situation, but we certainly are working and making sure we will have enough supply as and when we need it. Yes.
<A>: The question is how would we determine, if a case is material, it’s a very, very good question, its something that Biogen and ourselves and the FDA are talking about. And its something that we don’t have to answer to, just yet, I know that, I am not speaking for Jim, but I know he and I certainly spoke a lot about this, we can’t be in a position that every time a patient has a temperature, we have to report this, we have thousands and thousands of patients here. Number one, and number two, if you look at other drugs and you look at what happens with patients there isn’t a public discussion of each and every patient, that may have a an adverse events as minor or as major, as it may be. So, I think, that our view is working on the process as it has been put in place, which is you have the medical communities specifically investigators the agency and the companies, you have to take the time to understand, if there are any issues. So, I suspect you will hear less from us, than more going forward. Yes sir.
<Q>: (inaudible). Is there anything mechanistically about affect and mechanistically about Tysabri that was reason to believe that, it was a combination that may have caused this condition, close to (inaudible) modern therapies. And was, is there something mechanistically, about having a, as Mike disclosed this conditions to be developed in the presence (inaudible) today?
<A>: So, the question is, is there a reason to believe that there is a mechanism between the two drugs that could have triggered a, the proliferation of the virus and explosion of the JC virus in the
brand. Well, if you go to the next turn this is the or a, it worked hypothesis and that is that, it is one document that they interfere on, stimulates a down regulation of interferon gamma and then, up
regulation of TDS data. These are cytokines that are, they are potent. That is good when you try to control an MS lesion in the brain. But, at the same point, it is also well known, that these two changes can actually induce virus replication. Now, you will say, why doesn’t that happen in
patients who are on beta interferon. Well, the normal patient on Avonex, they have sufficient T cells surveillance. But, when you have an increased viral replication, you decrease the T cells surveillance in the brain under those circumstances, then you may provocate an uncontrollable
virus replication. These are processes that has been postulated to us from various sources. Then, if you add to that and those of you who follow the chat pages and the web pages on this specific topic, so that over the weekend there was a lot of comments about a paper that referred to the fact that indeed beta interferon induces soluble VCAM [ph]. Soluble VCAM [ph] actually absorbs part of the key cells on top of what is already locked with Tysabri. So, actually you get on almost complete blockers of all T cells surveillance. And then, if you want to speculate and you should be careful by doing that, then you could argue that yes indeed there is a pharmacokinetic event by which a beta interferon triggers a decreased clearance of Tysabri. So, if you want to put an hypothesis, then you
have the terrific storm that could drive a viral replication. Now, that is hypothesis, I am sure many of you could come up with other hypothesis. That is a hypothesis, that we will store and you could argue that there could be other reasons and, but this is one which we have felt being attractive and that we would like to explore.
<A – Kelly Martin>: Yes, the question is, were there two patients on steroids? And the answer to that is yes. And they were not diagnosed simultaneously. All the way in the back, sir?
<A – Kelly Martin>: The question is EMEA and the potential to move forward in Tysabri for both Crohn’s and/or MS. One of our important constituents up here is our regulators. Obviously, Europe is a big part of that. European group has a separate and distinct process from the US. If
you recall, we had accelerated review in the US and the Europeans do not have accelerated review. So, we are continuing along in the normal process in Europe. That has not stopped for both indications. The European regulators obviously now would like to see and hear from us with regard to these two adverse events and they clearly would like to see and hear from us with regard to what we find from the output with regard to the process that were going forward.
I can’t comment on their view, their timing as far as how they are reviewing Tysabri, I can only comment that they are still in their process, they do not have accelerated review. And additionally, particularly for MS, the European regulators were really only interested in the mono-therapy side of Tysabri. But the timeframe and the timelines of the European regulators are theirs, we are continuing down the process both Biogen and ourselves and we are working very hard to make sure that we stick to the timeline as closely as possible. Yeah.
<A – Kelly Martin>: The first question was, did either patient have neutralizing antibodies and the answer to that is no. Second question, with regard to if we find JC virus, what does that tell us in terms of where we find it, in terms of what kind of patients, you know, we have, if those patients are a combination patients that tells us probably a lot. If those patients are R.A. patients, it doesn’t tell us as much and would probably be a bit perplexing. And gain that’s why we are going through this
process – to be has throw and exhaustive as possible, to make sure that we – both companies understand all there is to know with regard to what happened.
Largest [ph] went through a hypothesis of what a fair amount of folks think might have happened.
But I think it will depend very much on which patients we have found anything in and what that would give us. Just to hypothesize, if we found three more patients that all were from the combination trial, that would statistically, clearly give us a zone that we would do extensive – more
extensive work and with regard to various DCs on what is occurring here between the combination of the products. Yeah, up in the back there.
<A – Kelly Martin>: Question is PML can be latent specifically the JC virus can be latent for some period of time, and what can we do in the safety trials with regard to that? I can largely expand on it to a degree – but the one thing we are always looking for the regulators, Biogen, ourselves was
opportunistic infections, because we you play around with the immune system that is something that you should prudently look for which we look for. It was 34 or 30? We had 34 of 38 different safety categories that we monitored for all those patients. And obviously we monitored placebo
against drug and in every category throughout all those patient populations this is why the safety efficacy ratio for this drug is so spectacular. There is hardly any change, and in some cases the
placebo patients are worse off than the Tysabri patients in things like depression and other safety issues.
But we didn’t test for JC virus; that is not something that anybody follows. We spoke with you know – Elan invented the Tysabri product in 1990. We have spent over a decade in this area. Our biologists in San Francisco have super sub specialties in all these areas, we have spoken to world
class immunologists for a decade. And I think it is fair to say we are with our Chief Medical Officer for the last couple of days, the JC Virus and or the word PML never came up in any discussion with any group of experts.
Hence that was one of the reasons, when we saw that, we want to take a very prudent aggressive approach with the agency to understand more. So that’s – we are as comprehensive as we can be from a safety point of view, and this is a very, very unusual occurrence, and given that unusual
occurrence, we did what we did. Sure.
<A – Kelly Martin>: We have had certain people on drugs for more than three years, so the safety beta and the safety trials are as long as we’ve been on drugs. We had certain patients that have been on drugs for almost three and a half years. And they have been monitored against all those things for three and half years. I mean the bodies are pretty complicated thing, there are a lot of other things that could be going on, and it’s often the case for people who suffer from these diseases, they have other things either along with them immediately or they have other things that become along with them as they go forward with their disease.
So the bodies are always changing, and as they change, we continue to monitor from a safety point of view, and that’s how you know we built up over time, safety there [indiscernible].
<A – Kelly Martin>: The question is a gentleman has a patient, a friend who has in the firm trial who is quite upset about not being having the drug available, we have gotten over a thousand communications a day from patients who are in a similar situation and we understand that, Biogen understands that, and as or more importantly, the FDA understands that. The only thing we can say that those people is given the unusual circumstance, we took this pause to be as thorough and
as prudent as we could to make sure we understood what was going on or at least had a hypothesis that could be proven or almost proven and that we are going to work as hard as we can with the FDA to finish this process as quickly as possible, as thoroughly as possible and to work
with them to get it back to be available to patients. We think we are getting harder in these seven days and we are using all hours in these seven days. So, we are moving as fast as we can.
<A – Kelly Martin>: But I think the process will take several months first to finish all these patients.
As regarding to that process, we are also talking to the FDA. So when we get more feedback from them, you know, we will keep the markets posted on that. Over here.
<A – Kelly Martin>: Two questions. One is trials, when will they start up again and the second, Dr. Ekman has dangerously educated me on some of the stuff but – first question is trials. We are working with the FDA and going through this process, obviously, trials are very well controlled and
you can make them even more controlled as far as frequency of visits. It’s certainly in all of our interest to restart those trials as quickly but as prudently as possible. It gives you more data, I won’t give a timeframe on it, but clearly from a trial perspective, that would be something that both buyers and ourselves would be very interested in doing as we believe would also be the best interest from an FDA point of view.
On the subset of patients, if you’ll let Dr. Ekman amplify some of my thoughts but there are – it’s a very difficult situation to be in there. Our patients that are MS patients who as we’ve seen from the data, current therapy does not work. They continue to relapse, relapses are permanent damage to the brain and that’s something that we are acutely aware of and the agencies are acutely aware of, maybe specifically they are even before.
<A – Lars Ekman>: No, I am not sure that we can predict in the specific patients, you know, someone who suddenly gets a lesion in their brain stem because you can’t and it’s always not the acute treatment, it’s not the way you use steroids or hypostatic drugs for acute treatment. Neither
of those treatments can be used in order to prevent. However you have to control the disease, we can never predict those patients who have failed current therapy are those who have not been on therapy and those who have break through on current therapy when will the next lesion come, will it hits the brain stem yes or no, will it make you blind, yes or no, and that is the trade off, that the FDA ultimately has to make between the likelihood of PML versus the consequences of the lesions in patients who have no effective therapy and I think that is the key element in this.
<A – Kelly Martin>: Okay, we will go ahead, yes sir.
<Q>: I have another question on Alzheimer’s. (Inaudible).
<A – Kelly Martin>: Okay, well, the question is – there was a conference last week in Italy, it was actually a Parkinson’s focused conference but there was some Alzheimer’s discussion, there was some discussion from external experts about our – the data from our 1792, which we went over the last July in Philadelphia, I am going to have Dr. Ekman go through the details and see he and his are driving all the Alzheimer’s piece. With regard to the beta secret phase topic with Pfizer, we are trying to work through that, they are trying to work through, so we are trying to find a way that we can both move forward with. We are both working on the target and we are trying to get a resolution where we can both on without being encumbered by either or we having good discussion actually with them on that. I don’t if you [indiscernible] for that data.
<A – Lars Ekman>: What was new this week at Parkinson’s and Alzheimer’s conference [indiscernible] in Italy was that, now there is two-year data – hat happens if you can decrease the amount of flex [ph] in the brain, and there is no indication that, yes, your cognitive functions,
effective functions, can be stabilized over time. This is now one and half year almost two years because since we started dosing. We have to remember that even if we dose the patients, we only dose them for part of the trial period, but we can still see the positive effects which is very
encouraging second question, you have was, have we seen something similar with the monotone antibody. Experimentally, we can repeat everything with 70, 92 with the monotone antibody. We do not have that data what you are asking for and with the monotone antibody.
<A>: Maybe a time for two more quick questions. So back here.
<Q>: Can you remind us what the funding arrangement is with Wyeth on the Alzheimer’s product line?
<A>: Funding arrangement with Wyeth is a 50-50 relationship, both funding and resources and input. They are a great partner, we work very well with them, we have done a lot of good things with them and vice versa. So, it’s a very straightforward 50-50 sharing of everything. All way the back, that's where we go, back to you.
<Q>: Question to (inaudible), could you give me some color as to what your PML experience has been (inaudible)
<A>: Right, well the question is let me rephrase the question. But, the question was supposes our PML experts and there was a one particular, I guess, conference in the last few days. Talk about PML for 2 seconds again PML is a very very rare situation, I think, it’s fair to say that there has been a lot of overnight experts anointed with regard to PML, that we have either heard from or read about or in some cases talk too, I will comment on all of the comments from that particular person.
But, I would say that, to answer the facts, the facts are that Tysabri from a data point of view, a monotherapy is a spectacular product. The data also suggests that from a safety point of view, again the way we have monitored it and the way we look at it is, we have seen no issues. It also –
contrast the fact as Lars just said they are enormous in the potential 100’s plus 1,000’s of patients, who have no choice with current therapy. So, as opposed to commenting on this specifics of the latest overnight expert on PML, I think that it’s important to understand those facts. And at the end of the day, Biogen sellers in the FDA will move forward based on those facts not on individual opinions that at least appear to me, to be based on low tax. I will take one more question, then we
will have turn the room. Yes sir.
<A>: The question is, do I have an opinion, or do we have an opinions on the FDAs decision to halt the trials and other similar agents, I think, it's very logical. It will ill-logical to us, if there is a question or there was something that we need to understand more about Tysabri, specifically and allow the other trials to go on. I don't know, if Lars has any further views on that, but I think, that’s a very logical something that we expected and something that we assumed would happened. So,
with that we appreciate your time, we are very happy to be here and I am sure we will chat with some of you after this.