Exhibit 99.1
CAPSULE ENDOSCOPY HIGHLIGHTS AT DIGESTIVE DISEASE WEEK 2006
CONFERENCE CALL
FRIDAY, MAY 26, 2006
10:30 A.M. ET
OPERATOR: Good day, and welcome, ladies and gentlemen, to this Given Imaging
conference call. At this time I would like to inform you that today's call
is being recorded and that all participants are in a listen-only mode.
Before we begin I would like to read the following regarding
forward-looking statements. During the course of this conference call
participants may make projections or other forward-looking statements
including the results of clinical trials and future use of PillCam capsule.
We wish to caution you that the statements reflect expectations and that
actual events or outcomes may differ materially. You are kindly referred to
the risk factors and cautionary language contained in the documents that
the Company files with the Securities & Exchange Commission including the
Company's annual report on Form 20-F filed April 7, 2006. The Company
undertakes no obligations to update any projections or forward-looking
statements in the future. At the request of the Company we will open the
conference for questions and answers after the presentation. I will now
turn the conference over to Mr. Mark Gilreath, Senior Vice President of
Global Marketing. Please go ahead, sir.
MARK GILREATH: Thank you. Good morning. Yesterday marked the completion of
Digestive Disease Week 2006 in Los Angeles. Over the next half-hour we will
review some of the highlights from the meeting and the conversation will
remain focused on clinical topics. Following the call our physician guests
will be please to take your questions. I am pleased to join you today with
two very special guests: Dr. Asher Kornbluth, Associate Clinical Professor
of Medicine at the Mount Sinai Medical Center, New York; and Dr. Douglas
Faigel, Associate Professor of Medicine at Oregon Health and Sciences
University in Portland, Oregon.
Over 15,000 people attended this year's DDW with the participants composed,
about 50/50 U.S. and international. There were 86 posters and abstracts
presented on capsule endoscopy and today our guests will review the
highlights of the meeting including Crohn's disease, our newly
approved AGILE Patency Capsule, esophageal varices, iron deficiency anemia,
and the role of capsule endoscopy on clinical outcomes. Well, let's get
started. Dr. Kornbluth, if you could kick us off, please.
DR. KORNBLUTH: Good morning, everyone. This year's capsule presentation is
basically corroborated and in fact indirectly or directly confirms the
safety of capsule in Crohn's disease. The big barrier to its more
widespread acceptance in Crohn's disease was a concern about the stricture.
Given has a new AGILE Patency Capsule and what it revealed was that in
people with suspected strictures for whom previously we would not give a
capsule, the Patency Capsule would dissolve in patients and reveal that
these patients were safe for capsule endoscopy. All patients who have the
AGILE Capsule pass uneventfully were able to undergo the standard capsule
endoscopy, and I think this broadens the marketplace a great deal for
patients with Crohn's disease.
There is data now that the combination of a capsule with the CT shows by
far the best imaging of the small bowel that can directly impact on
therapy. We're going to have a couple of new therapies most likely within
the next 12 to 18 months with Crohn's disease and knowing the full extent
of the inflammatory lesions of Crohn's might directly impact on the use of
these more potent therapies that we wouldn't use lightly. The capsule
images will expand the extent and severity of our assessment of Crohn's
disease because it does allow us to see the mucosa throughout the small
bowel where we were formerly limited to looking at the ileum with a
colonoscopy or having a much grosser look, so to speak, with the
traditional X-ray small bowel series where a great deal of lesions were
missed and underestimated. I think the most important of findings was the
sort of -- the finding that the capsule was safe after the AGILE and a
number of papers presented in abstract form that corroborated our thought
that this is a very sensitive tool. It can clarify the diagnosis of
indeterminate colitis into Crohn's disease depending on the patient
population with high accuracy. It demonstrated utility in evaluating
patients after medical therapy to assess the mucosal healing. Mucosal
healing has become a new standard or even buzz word for new therapies in
Crohn's disease. We've formerly been limited to assess mucosal
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healing with a colonoscopy and examination of the ileum which as we know
can underestimate mucosal inflammation by a great deal.
So having the combination of ileocolonoscopy for the bottom part and the
mucosal imaging with the capsule from above gives us the best idea about
the value of the newer therapies and I think that's going to be an
important potential use of the capsule, as well as using it to assess the
mucosal healing. Also in clinical trials and perhaps in assessing patients
with clinical outcomes that are somewhat equivocal with our standard
therapy. I think with proper pre-evaluation of patients with capsule in
terms of assessing patients with high likelihood of Crohn's disease but
with negative prior exams, the capsule is turning out to have a very high
probability value and positive predictive value. And on the other hand, the
flip side of that is a negative capsule study in patients with other
negative studies effectively rules out the Crohn's disease and really
prevents us from starting the patients on what can be potentially harmful
medications and mislabeling patients with Crohn's disease.
MARK GILREATH: Thank you, Dr. Kornbluth, that's an excellent summary. Let's
transition now to the application of PillCam ESO with varices with
Dr. Faigel.
DR. FAIGEL: Thanks Mark. Well, varices of the esophagus form in patients who
have advanced liver disease. They're a common cause of hospitalization when
they break and bleed. Mortality of a single episode of variceal hemorrhages
are in the 20 to 30% range. That means 20 to 30% of the patients die if
they start bleeding. We have therapies now that we can give to patients if
we know they have large varices that do a pretty effective job of reducing
that risk of bleeding and thus reducing that risk of death. But that
requires currently that the patient undergo a standard sedated endoscopy to
look for the varices to see if they're there so that they can get these
treatments. There are some significant barriers to patients doing this,
especially patients with liver disease who often have a history of
alcoholism or drug abuse and they're reluctant to go into endoscopy and
they're very difficult to sedate for endoscopy.
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As a result probably no more than 30% of the at-risk population with
cirrhosis get that endoscopy and have an opportunity to get the benefits of
therapy. So PillCam ESO allows a relatively quick and minimally invasive
way of imaging the esophagus in esophageal varices and there have been two
published reports on this already in small studies showing very high
sensitivities for detecting varices well over 90%. We're actually part of a
multi-center trial now looking at a broader range, broader spectrum of
patients.
There wasn't a lot from DDW on varices this time. There was a study from
France -- showing high sensitivity of varices. There was also another study
from New Jersey, again showing complete concordance between endoscopy and
the ESO, both of them agreeing when varices were present. So I do think
that this is going to turn out to be another important tool for taking care
of cirrhotics.
MARK GILREATH: Thank you, Dr. Faigel, I think that cost effectiveness position
seems quite favorable to PillCam ESO. Can you give a few comments now on
the bleeding application particularly within IDA patients?
DR. FAIGEL: Yes. So of course when the capsule came out in 2001, the primary
use, actually probably most of the reasons patients get it nowadays is for
bleeding. If bleeding is sort of slow, what happens is that the patient
loses all their iron stores, and they can't make new red blood cells any
more and they become iron deficient. That's actually the most common cause
of anemia in the United States is iron deficiency. Patients who have iron
deficiency who are males or are postmenopausal females usually are iron
deficient because they're bleeding from their GI tract somewhere and it's
long been our recommendation that they go upper and lower -- undergo upper
and lower endoscopy. Less defined has been the role of capsule endoscopy.
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There was a very nice study from Italy in 189 patients who present with
iron deficiency anemia and then they had a very specific algorithm for how
they were going to assess them. They did an upper endoscopy, they did a
colonoscopy, they did a capsule, they did small bowel follow-through, and
they also did a CT scan called an entero CT. What they found was that about
75% of the patients will have a diagnoses just from the upper and lower
endoscopy. That meant 25% will be undiagnosed. Capsule endoscopy was done,
and this improved that diagnosis rate up to 96% and was better than the
radiological methods for finding lesions with the exception of tumors where
CT was equivalent to capsule finding tumors. So I think that the algorithm
then really ought to be upper endoscopy, lower endoscopy, and then capsule
and then thinking about this entero CT, particularly if you're concerned at
all that there might be a tumor.
MARK GILREATH: That's very helpful. Can you take some of that -- take more
of the global approach now and consider how these things impact clinical
outcomes and maybe how people integrate these things into their practice?
DR. FAIGEL: Well, if we're talking about small bowel capsule and bleeding, this
is a serious problem for some patients who are requiring blood
transfusions. I think that this, for iron deficiency for example which is a
very, very common problem, I think it really highlights the importance of
doing a complete evaluation in order to improve clinical outcomes. There
were a number of follow-up studies presented at DDW, all fairly large, all
with more than 100 patients again showing high diagnostic yields in the
range of 50 to 70% and finding in general that if a significant lesion is
found, allowing specific treatment, that follow-up bleeding was rare. On
the other hand if a lesion -- if the capsule was completely normal, then in
follow-up -- only about 10% would be found to continue to have bleeding. It
seems to have good negative predictive value which is important, but also
good positive predictive value in terms of being able to identify a lesion
and then give a very specific therapy to try to get that patient to stop
bleeding, and in fact that strategy does work.
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Another thing I would like to just talk about where we were talking about
bleeding is about double balloon enteroscopy because I think there has been
a lot of questions as to how capsule and double balloon play together. This
is a form of deep intubation of the intestine with an endoscope. This was
developed in Japan, and in Japan they are reporting very deep intubations
of the small intestine, in fact being able to see almost the entire if not
the entire 22 feet of small intestine.
There is a study from Germany on the double balloon enteroscopy, now this
is more of a population that's similar to ours, a Western population. They
only reported being able to get in about 5 feet into the small intestine
rather than 22 feet. Now, in this study they did capsule endoscopy and
double balloon enteroscopy. The capsule and double balloon agreed almost
all the time as to what the lesions were. I think this shows that the role
of capsule in the area of double balloon is going to be do a capsule first,
use that capsule information to decide whether to use double balloon and
also how to use double balloon because the endoscope can be inserted
through the mouth or it can be inserted through the rectum and the colon. I
don't think -- although a lot of people were sounding the death knell of
small bowel capsule when double balloon came out, given the difficulties of
doing double balloon and the expense, it is quite invasive and takes over
an hour to do. I think this will not impact on my usage anyway of capsule
endoscopy.
MARK GILREATH: Thank you, Dr. Faigel. I think we are hearing more consistently
now that these are complementary technologies. Any other highlights that
either one of you might like to mention from DDW before we turn it over to
questions.
DR. FAIGEL: Yes, there was one other thing that I thought was really
interesting. One of the things that Given has been doing is improving the
way that their computers and their computer algorithms analyze the images.
When the capsule first came out in 2001, it was regularly taking one to two
hours for a physician to review a study. There have been steady
improvements in the computer algorithms that look at the data so that you
don't have to look at every single picture obtained during that eight-hour
acquisition.
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In Rapid 4, the current version of the software, they have something called
the QuickView system. They also have the suspected blood indicator which we
have had before. How quickly is a little different, and, Mark, you will
have to correct me if I'm wrong on the technical details here, is that it
is going at a very fast rate looking on average at about every 100th image.
However, what it is doing is it's highlighting areas of interest that the
computer through the computer algorithm is saying these are interesting
areas. So when you go through QuickView, it is not just a random every
100th image. It is every 100th plus anything that it thinks is interesting.
There was a study from Madrid looking at the QuickView and comparing it to
sort of standard physician viewing, and they found that more than 90% of
the important lesions were found on QuickView. That's really interesting to
me. It doesn't mean you can get away without really doing the whole study,
but I think it really highlights what is going to be capable of having our
computerized algorithm systems doing to really improve physician review
time without any decrease in the sensitivity of the capsule enteroscopy.
MARK GILREATH: I think with each new version of software we're seeing real gains
in practice efficiency and now with Rapid 4, it has been a nice leap
forward from Rapid 3. One other thing I did want to ask before we
transition is I am not sure if you guys were participating in the plenary
session and the final lectures from Drs. David Fleischer of Mayo Scottsdale
and Robert Hawes, the President of the ASGE, and the Medical University of
South Carolina, they each were closing the session really looking toward
the future and the future of GI diagnostic imaging. Perhaps if one of you
participated, if you could comment on the lectures.
DR. FAIGEL: I was there. I am a governing board member of the ASGE. This is the
ASGE plenary session. Rob Hawes gave a lecture on disruption endoscopy, and
that is very much informed by the book by Clayton Christianson, "The
Innovators Dilemma" which I am sure many of our investors who are listening
are more familiar with than I.
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There has been a thought that diagnostic endoscopy, say putting a scope
inside to make a diagnoses, is likely to be disrupted by less invasive,
maybe easier to use, techniques that don't require a lot of operator skill,
and certainly capsule endoscopy really kind of represents that. After all,
this is just something that technically what do you do? You swallow a pill.
So it is not very difficult, and the data that gets analyzed, you don't
have to analyze it where the patient is -- it can kind of be analyzed
anywhere at any time. Dr. Hawes really focused on this as likely to be a
disruptive technology for diagnostic endoscopy. David Fleischer then kind
of reviewed capsule endoscopy and some of the things that have been
happening in it lately that will allow it to kind of take over what
endoscopy does. He focused on -- two things that really stuck in my mind
were number one, the ability to focus on a lesion. With an endoscope I can
go and move -- I can steer my endoscope and I can look at a lesion and I
can come back and forth and look at it again. The current versions of
capsule endoscopy really don't have that ability. However, at the plenary
session a type of a capsule endoscope that in fact was steer able albeit
enormously large and was an ex vivo study was described. We do believe that
it is going to be possible to have remote control capsule endoscopy.
Paul Swain, from England, who is a big innovator in this area has
previously described the ability to generate heat and provide cautery from
a capsule and that's done through a chemical reaction and Dave Fleischer
reviewed that, too, and said what's coming down the line is going to be
capsule endoscopy for diagnosis, capsules that we're going to be able to
control externally and capsules ultimately will be able to provide therapy.
MARK GILREATH: Thank you, Dr. Faigel. If there are no other comments, what I'd
like to do now is turn it over to questions.
OPERATOR: Thanks you. Today's question and answer session will be conducted
electronically. If you would like to ask a question, please do so by
pressing the star key followed by the digit one on your touch-tone
telephone. I'd like to remind you that if you are on a speakerphone, please
make
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sure your mute function is turned off to allow your signal to reach our
equipment. Once again, it's star one for questions.
And we'll go first to Lee Brown with Merrill Lynch.
LEE BROWN: Good morning, everyone. And thank you for providing this update
post-DDW. I just want to ask a question on PillCam ESO. First, I'll just
state that I am in solid agreement with the conclusions on the
double-balloon enteroscopy, I think several studies showed that not only
was capsule endoscopy superior to DBE, but that they were in fact
complimentary. But in terms of your statements on the PillCam ESO early on
in this call about it being cost effective, I'm a bit taken back by that,
because of there were two cost benefit analysis trials that were done, one
particularly by a Dr. Gerson. And it showed that EGD was less expensive and
more cost effective to CE.
And then, secondly, I was just wondering what your thoughts were on string
capsule endoscopy and how that might negatively impact Given.
DR. FAIGEL: Well, you know, the first thing is that the cost effectiveness
assumes that a patient is willing to undergo both an endoscopy or a capsule
endoscopy. The problem has been doing endoscopy in this population of
patients, and getting them to comply with this and their getting referring
positions to comply. So the cost effective treatment is the one that
patients are willing to do. That different compliance rates with the
different technologies has really not been taken into account.
Now I'm not an economist, but if only 30 percent of the patients will have
an EGD, but, 50 or 60 percent will have a capsule, then you're going to
capture a whole bunch more patients that you're going to be able effect
therapy with. Yes, the cost will be higher, but on the other hand, the
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benefit will be higher too, because you'll have a whole bunch of patients
who would never have gotten their beta block or never would have gotten
their banding, had they not had the capsule.
So, if we're going to look at head to head comparison, I think we're going
to need to take into account whether patient compliance rates are likely to
be the same. And I can just tell you for myself, I actually I have GERD and
I actually swallowed a capsule rather than having an endoscopy just because
it's so much more convenient. I think that is probably going to be true for
varices as well where these patients are really hard to scope.
LEE BROWN: Yes, and I would agree that this sort of analysis is highly - of
course, highly dependent on the variables. I don't know if you're familiar
with the Gerson paper, but I'll just throw out a few variables and I'm
curious if those were changed slightly if you would come to a different
conclusion here. They talked about detection rate with capsule endoscopy
needing to be at greater than 86 percent for cost effectiveness, everything
else equal. Gerson assumes 78 percent, just interesting -I'd be interested
to hear from you and from Given if they think they can achieve somewhere in
terms of detection in the 86 percent vicinity.
DR. FAIGEL: I think that's true. Most of the - you know, most of the data we've
seen are small studies and they have their inherent limitations. But in
terms of proof of principle I think it's absolutely possible to achieve
that rate with the current capsule. And, you know, they're making - they're
going to have a new esophageal capsule, and a new ingestion - they all
ready have a new ingestion protocol. And I think it's going to be better.
I was going to say something else about cost, yes. OK. So now, also by cost
analysis, if you've read on this, that actually the cheapest thing to do is
to just put every cirrhotic on Propranolol. Propranolol is a beta blocker.
It's very cheap. It's about the cost of aspirin. I think right now and just
put them all on that. You know, you're a cirrhotic, just take a beta
blocker. We don't do that because no one will take the stuff. It's very -
it has a lot of side effects, particularly in cirrhotics.
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And as an approach, while the model, which is not data, it's just a model
suggests that it is the best way to go from a money point of view, when you
try to actually do it in the real world it doesn't work.
LEE BROWN: Interesting. Along that line, and then I'll get off, because I need
to let other people on here, so I apologize for that. But could you explain
why someone would want to subsidize endoscopic band ligation? I'm not quite
familiar with that. And that was also part of the study you just
referenced.
DR. FAIGEL: Well band ligation, what that is, so you have these varicose veins,
and if you do endoscopy, they look like this big blue snakes right
underneath the surface under the lining of the esophagus. And what you do
is you just - you put rubber bands on them. And this causes the blood to
clot in them, and then they sluff off, and that will eradicate these
varices And there are now studies - we've known that that's a good way to
treat them when they're bleeding. And now there's studies both from the
United States and abroad showing that they'll prevent, subsequent bleeding
and lower mortality.
The current recommendation is still for most patients to be - to go on
pharmacotherapy with a beta blocker like Propranolol rather than the doing
the banding, because the banding is more invasive and carries some risk.
But certainly a lot, more and more patients are undergoing banding to
prevent them from bleeding later.
LEE BROWN: OK. Thank you very much for your time. It's very much appreciated.
OPERATOR: We'll go next to Ed Shenkan with Needham & Company.
ED SHENKAN: Thanks again, Given for providing this forum, it's a good recap of
DDW. I have a question for Dr. Kornbluth. On Crohn's when you have a
patient that's been diagnosed with Crohn's, how
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often subsequently do you monitor that patient with an endoscopy currently?
And now that you have the capsule, and especially the AGILE capsule, how
often to you expect to monitor those patients? And what impact do you think
your colleagues - you know, how will they change their protocols?
DR. KORNBLUTH: OK. It's a great question. I think most of the monitoring we do
on our patients are going to be clinical monitoring, you know, basically
asking how the patient is doing in exam and labs, if they have a potential
if they have a component of colonic disease, these patients will continue
to be colonoscoped. If patients have the typical small bowel symptoms,
we're not going to repeat capsules on a regular basis. If they have
unexplained symptoms that we can't discern by the colonoscopy and peaking
into the ileum, these are the patients that will get repeat capsules.
Again, now that we have the AGILE capsule, I think we're going to be using
the capsule for follow up more often. I wouldn't say that the majority of
Crohn's patients will have capsules with repeat flares. I think it will be
a minority of patients. But I think what was holding it back was the lack
of something that could rule out a stricture, and now we have that.
ED SHENKAN: So now that you have the AGILE capsule, would you consider doing
routine monitoring with the capsule in those patients once a year? Or
you'll just ask the questions and look for symptoms like you described?
DR. KORNBLUTH: Yes, I don't think it will be done once a year. I think it's
going to be based on clinical presentation whether we make a clinical
diagnosis as we usually can. It's the patient with the unexplained symptoms
that will get the capsule.
ED SHENKAN: And I have a question for Dr. Faigel. Attending DDW, I went to see
your poster, where you compared the Olympus capsule to the Given capsule.
And in your conclusion, one of the things you said was resolution and
quality of images using Olympus software rated better than
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resolution and quality of images using the Given Rapid 3. I wonder if you
could just frame that for us, and tell us is that important for diagnostic
capability? Do you think it might be?
DR. FAIGEL: Well, you know, the way the study was designed was that at after
we're done reading every study, and they were read blindly, so for example,
when I was reading them, I would read an Olympus capsule on patient A, but
I would not read the Given capsule on patient A, somebody else did that.
Every patient swallowed both capsules.
At the end you'd rate the quality of the imaging, and, you know, that's how
the data shook out. You know, my own take on it is that the Olympus image
is very sharp. I believe it's using some type of a computer algorithm to
sharpen up the edges, because they told me it's the same chip that's in the
160 series endoscopes, but it's a very different looking image than the
ones we see on the 160 endoscopes.
The problem I had was that everything looks very abnormal. You know you'd
see all of these edges, and it tended to make the edges look red. And I had
a hard time sometimes, telling was I looking at active bleeding or not. And
that was my biggest problem looking at it. Remember, there's only 16
patients in that study, so it's hard to generalize. Looking at other types
of pathology it seemed to pick it up as well as I would expect a capsule
endoscope to do. So is it a PillCam, does it take pictures of the small
intestine? Yes, it does. Is it better than the Given, particularly if
you're going to look at like clinical relevance and clinical outcome? Very,
very unlikely to be true.
ED SHENKAN: But you only did a couple of the patients in that 20 patient study
it sounds like?
DR FAIGEL: Yes, right. Right. I mean it's a bigger study. We've reviewed more
than we've reported, but I haven't seen the data though on the larger
study.
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ED SHENKAN: What kind of review time, did you find, you know, comparing those
two systems, was it similar?
DR. FAIGEL: We used two different dates software. The original software was very
clunky and slow and it took over an hour. The software that they've shown
at meetings is - rather similar to Rapid 3 in terms of how it works and
about how fast you can go. So I'd say that their current software is very
comparable to Rapid 3 in terms of review times.
ED SHENKAN: OK. That's helpful. And then the last question is about the protocol
change, and Mark, maybe you'll help us to understand. Attending DDW, I did
understand that you're changing the protocol for the ingestion of the
esophageal capsule. Could you tell us why you're doing that? What better
diagnostic outcomes do you expect as a result of that?
MARK GILREATH: I can comment on the white paper that was presented, and
Dr. Faigel, I don't know if you've seen that white paper. Basically a team
look at eight different scenarios of ingestion and selected one that was
the optimal ingestion protocol. The primary driver there was to eliminate
the bubbles, that were typically apparent around the Z line. And I think
it's been very successful in doing that. But perhaps, Dr. Faigel can
comment further.
DR. FAIGEL: Yes, I mean that's a - Mark is right, that sometimes there are
bubbles right at the Z line. This is probably due to air refluxing up out
of the stomach essentially micro burps if you will. And it kind of makes a
little froth there, and it interferes with your ability to see the
squamo-columnar junction where the squamous mucosa of the esophagus bumps
into the pink columnar mucosa of the stomach. And you need to see that in
order to tell whether there's Barrett's or not.
Original protocol had patients lying on their back to swallow the capsule.
And we were seeing bubbles. They actually did a study in patients in Israel
with, like Mark said, I think it was eight
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different protocols. And what they found was that a protocol with the
patient lying, I want to say on the right side, is that right Mark?
MARK GILREATH: That's correct.
DR. FAIGEL: Yes, it's on the right side, gave them a better image. The reason
why that's true is that the stomach is a left sided organ. When you ride -
when you're on your -if you're on your left side and you drink water the
water will then pool on the left side away from the esophagus because the
esophagus is in the middle of your chest. If you're lying on your right
side, though, then the water pools up right up against the bottom of the
esophagus, and so there's no way the air can kind of percolate up there and
form bubbles. In this little study, they found that they had much better
imaging of the Z line and they were able to see, and if you divide it into
quadrants they were able to see more quadrants of the squamo-columnar
junction with this protocol. So I think that's likely to improve the
detection rates for esophageal pathology, but, you know, of course, we
don't know that that's true, but it's just a supposition which is probably
right.
MARK GILREATH: And there was just one other element to the original protocol is
the patient had to be lying down, I mean lying in a certain angle, and then
a different angle. It was very difficult for the staff to be compliant to
this more complicated procedure and now lying on the right side is much
more simplified, and something we're able to reproduce more easily.
ED SHENKAN: So just to summarize gentlemen, you're finding with the new
protocol, you get less bubbles. And you think you'll get better diagnostic
capability, although that hasn't been confirmed.
DR. FAIGEL: Yes, it was less bubbles, but it was also they saw more of the Z
line. So it wasn't just they saw more bubbles, they actually saw more of a
relevant anatomic feature that they need to see.
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ED SHENKAN: Could you explain why it's important to see the Z line, please?
DR. FAIGEL: The esophagus is lined by squamous mucosa it's like the inside of
your mouth. And when you look at it endoscopically it has sort of this
pearly white appearance to it. The stomach is columnar mucosa and it's
pink. Barrett's esophagus is columnar mucosa like the stomach it's pink
also. To diagnose Barrett's esophagus what you want to see is that line.
The Z line is where the squamous mucosa and the columnar mucosa meet. And
you want to see that there are tongues and extensions of this pink lining
up into the tubular esophagus.
In order to do that, you need to be able to see the Z line, and say that's
a normal Z line, as opposed to seeing this pink lining extending up into
the esophagus.
ED SHENKAN: That's helpful. And to make a definitive diagnosis, do you need to
do a biopsy then for Barrett's?
DR FAIGEL: Absolutely. You cannot biopsy - you cannot make a diagnosis of
Barrett's without a biopsy showing what's called intestinal metaplasia.
ED SHENKAN: As a follow up from the esophageal capsule, you'll do a biopsy then
with the scope, is that right?
DR. FAIGEL: Right. So the protocol would be do esophageal capsule. If that's
abnormal, then the patient gets referred for an upper endoscopy with
biopsy.
ED SHENKAN: When you do the scope of the esophagus, do you typically go past the
esophagus and look at more anatomy? Or do you usually not?
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DR. FAIGEL: No. You always do a full and complete upper endoscopy. And that
means looking at the esophagus, the stomach and the first part of the small
intestine called the duodenum.
ED SHENKAN: So now that we're looking at a disruptive technology, the ESO pill,
it only takes pictures of the esophagus. Is that less favorable compared to
what you're doing then, since it's - you know, you're viewing less anatomy?
DR. FAIGEL: I mean it's less imaging of the GI tract, absolutely. And pathology
of the stomach and the intestine can and will be missed. The question, you
know, one of the questions is, of course, is endoscopy for Barrett's where
you look at the stomach or the duodenum is that really more than you need?
In most patients who have just typical heartburn symptoms, who don't have
any warning symptoms. They're not bleeding. They're not having a lot of
pain. They're not having weight loss. They just have uncomplicated reflux
symptoms. Then probably more than just an esophagoscopy or looking at the
hiatal hernia is probably more than they really need. And that's why
capsule might be able to fit in there.
We do need data, which is probably going to need to come very large post
marketing studies looking at, you know, what kinds of pathologies are
missed in the stomach and the duodenum, how often that happens, and whether
it's clinically relevant. My sense as a gastroenterologist is that in the
uncomplicated heartburn patient that it's very rare to see relevant
pathology in the stomach and duodenum. But that's an opinion.
ED SHENKAN: Thanks, again, Given for putting this on. It's very helpful.
OPERATOR: We'll go next to Stanford Rothschild with Rothschild Capital
Management.
STANFORD ROTHSCHILD: Yes, thanks. I wondered whether there was a patency or
AGILE capsule being developed, or already developed by Olympus and whether
Given has any protection on theirs?
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DR. KORNBLUTH: I'm not aware whether a patency is being developed by Olympus at
all. I have no knowledge of that whatsoever.
MARK GILREATH: Nor do we at Given.
STANFORD ROTHSCHILD: OK. Thanks.
OPERATOR: We'll go next to Mark Miller with RBC Dain Rauscher.
MARK MILLER: Good morning, gentlemen. In reading what I've read, there would
seem to be a reluctance of physicians to use the pill in general. Are you
finding them to be more receptive to this?
DR. KORNBLUTH: I'll address this from a Crohn's point of view. I think with the
AGILE, it really lowers the barrier to use for a very broad population of
patients. I think the other area that I didn't touch upon, but is a huge
potential market that is just starting to be studied is Celiac disease,
because there are those patients that can be easily screened with
serologies which are just blood tests that are very non-invasive. And if
those patients have duodenal biopsies, which Dr. Faigel mentioned is part
of every upper endoscopy, they generally undergo biopsies and that's been
considered the gold standard and if they have a negative biopsy with a
positive serology, and the serology was until now considered a false
positive.
But what we're finding with some of these patients is that they have
downstream endoscopic or capsule lesions that probably make the diagnosis
of Celiac even in the absence of positive duodenal biopsies. So it might be
that the very large number of patients whom we biopsy for Celiac disease
and who are negative, will now have capsule endoscopy to see if they can be
picked up to have Celiac disease. In Celiac disease is sort of ideal for
capsule because there's no concern whatsoever of strictures, so I think
that will open another huge potential market, which
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in fact is probably bigger than inflammatory bowel disease, if we have some
prospective studies come back with the sort of similar finding that we've
seen in some of these smaller series.
DR. FAIGEL: And I'd just like to comment on that too. I think the reluctance or
enthusiasm for capsule parallels the clinical experience, and the amount of
data, and the number of publications for each capsule application. For
example, in obscure GI bleeding, where you're thinking about something
bleeding in the small bowel intestine and you're doing a small bowel
capsule, I don't think there's any reluctance at all. And I think the
enthusiasm kind of decreases with the experience. So I think the next most
enthusiastic area is IBD, where there's data, but not as much in bleeding.
And it goes down from there with esophageal and emerging things like Celiac
or looking for tumors in high risk patients. And, you know, I think a lot
of that will change as more and more data comes out, will clarify the role
of capsules in very specific disease entities. And then, that will tell us
whether we're going to do a lot of them or a few of them.
MARK GILREATH: Yes, let me just add to that. I think in the past month, it was
really helpful for many physicians to see the ASGE provide a technology
update. And Dr. Faigel since you're part of that leadership, perhaps you
can comment on how physicians perceive that.
DR. FAIGEL: Well, you know, it's a review of the technology. I'll just discuss
how they're created. We have a committee called the technology committee
and they review the literature and prepare documents, which is then
reviewed by the governing board, which is what I'm a member of. And then,
based on input from the governing board, which basically serves as the
editors, you know, a statement comes out regarding it.
What's nice about these things is they're very concise, evidence-driven
reviews of the technology and also of the data looking at efficacy and
comparative studies. And, you know, this is the most recent one from our
organization, so it has the most up-to-date data. I think physicians look
to this.
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We also have another committee called the standards of practice committee.
And we have a guideline on the evaluation of obscure GI bleeding for
example that heavily references and refers to capsule endoscopy and
recommends its appropriate use.
MARK GILREATH: Yes, I think that the other important piece for us all to be
aware of is that that statement from the society which was absent until
this last month with such update on expanded indications will be an
important factor as payers consider reimbursement across the country,
Medicare, and non Medicare.
MARK MILLER: Regarding this new market you just mentioned, what would have to
take place for you to actually consider working it into your future
estimates?
DR. KORNBLUTH: OK. So I'm not in a position to give you information in terms
financial estimates but I can tell you that if there are a couple of
prospective series that come forward, and I'm aware of at least one that's
being submitted for publication now, that indicate that there are findings
that are positive, that are not visible or biopsiable with a standard upper
endoscopy and that can impact on the treatment of these patients, which is
essentially low risk which is a gluten-free diet.
And if you ask is it so low risk that we should just treat patients
empirically with a gluten-free diet, I can tell you even though it's low
risk, it's quite a burden to tell people they can't have wheat, barley and
rye. To put it in context, that means you can't have bread or pizza, or
maybe for some people most importantly, you can't drink beer. So you're not
going to put a lot of people on a gluten-free diet without a firm
diagnosis. And again, it's an easy diagnosis to make. If you think of it,
there's this very prevalent concept that we're just quote unquote at the
tip of the iceberg, and that the Celiac disease population in this country
is probably about one in 120 people have undiagnosed Celiac which might be
full blown with a lot of diarrhea, abdominal pain and bloating, what we
might otherwise have called irritable bowel. Or there are people with much
more subtle
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Celiac disease that we're just not picking up on biopsies, when our
biopsies are limited to the proximal duodenum. And you can do the
arithmetic, if it's prevalent in more than 120 people or so, who don't have
a blown syndrome there's a huge potential market for screening patients
with capsule.
DR. FAIGEL: And just to touch on it too. I think there's also a potential
application, the follow up of patients with Celiac disease. It's very hard
to stay on this diet. Patients often will relapse, you don't know why
they're relapsing. And Celiac disease carries a cancer risk for both
lymphoma and adenocarcinoma of the small intestine. And frequently, these
patients have to undergo repeat endoscopies looking for why they are still
symptomatic. And it may be that capsule will have a role in the follow up
of these patients as well.
MARK MILLER: Do you have any idea when there might be some follow up regarding
these studies, that you could present to us?
DR. KORNBLUTH: Well I could tell you that in terms of Celiac Sprue, there's the
working group that's going to be meeting in Paris in about two weeks, which
is a follow up from a large consensus group that met in Florida about six
weeks or two months ago. And they're going to have a consensus statement
come out shortly after that. And knowing the preliminary consensus
statement is that capsule will definitely have a role in a large subset of
patients. And again, we've probably vastly under-screened patients with
irritable bowel, which is a huge population of potential capsule patients.
I think there's going to be a strong consensus that the capsule does have a
additive role to what we've traditionally done, which is a serology and a
biopsy.
OPERATOR: We'll take our next question from Yair Reiner with CIBC.
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YAIR REINER: Hello, thanks again, for making yourselves available to us. A
couple of questions, first of all in the AGILE capsule, can you give us a
sense of what the cost is right now for the capsule? And whether insurance
companies are reimbursing for it?
MARK GILREATH: The cost of the product is $100. And reimbursement is on a
case-by-case basis.
YAIR REINER: OK. I wanted to ask both doctors, if you're noticing more awareness
on the part of your patients about capsule endoscopy, and whether you have
patients coming in who are actually requesting it and seeing if it's
available for their perspective conditions.
DR. KORNBLUTH: I'll address from the Crohn's point of view, is that patients are
aware of it. They need to have the doctor indicate to them that it's an
appropriate test that is beyond the standard small bowel series. I could
tell you that uniformly patients who have had small bowel series don't want
to repeat those again. And if they've had a diagnosis of Crohn's made with
small bowel and now they're having symptoms that we can't explain, they
would jump at the opportunity to have a capsule study instead of a small
bowel series.
In terms of CAT Scan to image of small bowel, I think there's big strides
being made there, but there is a substantial cost with the CAT Scan of the
abdomen and very substantial radiation exposure. The biggest barrier in my
mind is using in Crohn's patients was the concern about strictures, even if
it's only about five to seven to eight percent. But I think with the AGILE
capsule, we could eliminate that concern to a very, very large degree.
YAIR REINER: Good. Thank you very much.
OPERATOR: And today's final question is a follow-up from Lee Brown with Merrill
Lynch.
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LEE BROWN: Hey, thanks very much for fitting me in. There was a statement made
that the Olympus software and interface was on par with the Rapid 3.0. Is
it fair then, to say - to characterize the Olympus interface and software
as perhaps inferior to the Rapid 4.0 which is the latest iteration for
Given?
DR. FAIGEL: Well first of all when I say it's on par, I'm just talking about
image, being able to look at the pictures, find images, do that sort of in
a quick way and select images for thumbnails. Being able to that, it's
similar to Rapid 3. There are other things that Rapid does like as a report
generator and things like that that they're still working on. So there are
other things about it that are not quite there yet. But, I'm telling you
the sort of the beta stuff. And I'm sure it will be - my guess it will be
complete - when they start delivering systems in the United States it will
be completely comparable to Rapid 3.
Whether it's better or worse than Rapid 4, Rapid 4 has some developments,
primarily in how the images are displayed, and the algorithms and how fast
you can go through that are better than Rapid 3 but there's no head to head
comparison to the Olympus. You know, it's just sort of a supposition, you
know. A equals B. C is better than B. So C must be better than A. I mean
it's just sort of mathematical.
LEE BROWN: Sure. And then just lastly, and thanks again for the call, the
studies that say that the real time imaging is a benefit for Olympus I
guess I'm just curious how you feel about that, since I would expect the
majority of these procedures to be on an outpatient basis.
DR. FAIGEL: I mean Olympus is - apparently is going to have - you know, you'll
automatically get the real time imager when you buy a system. I think
Given, you have to buy it as an add on. Given has one too. So I mean I they
both have it.
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LEE BROWN: I guess the question is, do you see it as a benefit? I mean is there
a reason to have it, I suppose?
DR. FAIGEL: Sure. I think there's a reason to have it. For example, if you want
to know if the thing has gotten out of the stomach and whether you need to
do something to get it from the stomach into the small intestine. I think
the most common reason to have a failed small bowel capsule is because it
didn't leave the stomach. And that would allow you after a couple of hours
to take a quick picture and see if it's in the stomach or not.
And similarly, you could, you know, at four hours see if it's in the colon,
and if it is then the patient is done and they can go home. They don't have
to hang out. I don't like letting my patients, you know, wander around the
city with five or $10,000 worth of my equipment on them. So I make them
stay pretty close to the facility here.
LEE BROWN: Interesting. I wasn't aware of that. OK. Well thank you very much.
DOUGLAS FAIGEL: That's my practice anyway.
OPERATOR: And that concludes the question-and-answer session. I'd like to turn
the conference back to Mr. Gilreath for any concluding remarks.
MARK GILREATH: Thank you very much. I just want to say thank you to Drs.
Kornbluth and Faigel for joining us today. We look forward to providing
clinical updates following the European ICCE meeting in Paris which will be
in early June and also the ACG and UEGW meetings later this year. Thank you
very much.
OPERATOR: This concludes today's conference call. We thank you for your
participation and you may now disconnect.
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