Bob Hollar:

Hello!

Dr. Ostermann:

Hello, its Dr. Molly Ostermann.

Bob Hollar:

Good afternoon Dr. Ostermann!

name correctly?

Am I pronouncing your

Dr. Ostermann:

Yeah, very good.

Bob Hollar:

Thank you! Thank you so much for joining me this

afternoon and lets work to our conversation. What I
would like to start it out with Dr. Ostermann, if it is all
right, is to go over some of our kinda ground rules to
make sure you understand everything and everything is
agreeable to so...

Dr. Ostermann:

Sure.

Bob Hollar:

If you will, I will ask you a moment. I will explain that first
of all introduce myself. I am Bob Hollar and I am with the
company Giles & Associates and we are a consulting firm
so working with the client currently in the healthcare
industry who is investigating a vaccine for CMV and...

Dr. Ostermann:

Very good.

Bob Hollar:

For that, under that general area we are interested to

understand more about your medical practise and the
patients that you managed that might be at risk for CMV,
and also to tell you a little bit about this proposed product
and get your reaction to it. I am going to be recording our
interview today if thats all right with you.

Dr. Ostermann:

Sure.

Bob Hollar:

At least for the purpose of being able to write up a report

from our conversation. I am well a world worst taker of
note, and to try to do so, I would become
incomprehensible on the phone and so rather than have
that happen, what I am going to do is record our
conversation today and go back later to kinda rebuild my
report. But in that report, none of the information or none
of the specific things that you talk about today will be
reported back to our client with your name. So, all the
comments and the thinking about a reaction to the
product will all be reported in aggregate. So, you are

assured there is confidentiality in that regard. So, does

that all sound all right too?
Dr. Ostermann:

Sounds good.

Bob Hollar:

Okay, great! So, I have a lot of specific questions that I

like to go through and I apologize if some of these things
become repetitive. It is definitely not my intent to do
that, but sometimes I dont manage the conversation well
and I realize that you may occasionally mention things
that I end up asking about later and I apologize in
advance for that only because I have kind of a list of
things that I need to get to you and I want to make sure I
do them all. But towards that end, I think it would be
really helpful for me if I would just sort of give you the
freedom to actually describe your practice and what kinds
of patients you see and what your specialty is and a little
bit about how CMV enters into your practice and patients.

Dr. Ostermann:

Sure. So, I am a consultant in a large teaching

hospital in central London and the hospital has a
very large critical care department, but also has a
very large renal unit and it is a tertiary cancer
center and I work in the intensive care unit and I
also work in the renal unit. So, I routinely look
after patients who are immunosuppressed and they
are either immunosuppressed in spite of their renal
illness or they immunosuppressed following a renal
transplant or a kidney-pancreas transplant, or they
are
immunsuppressed
as
the
result
of a
chemotherapy for cancer, and I come across CMV in
the renal unit either in patients who are inpatients
admitted to the ward or in the outpatient setting.
So, these are transplant patients who have CMV
disease but are not sick enough to be admitted and
they are being followed up in the outpatient clinic
and I come across CMV disease in the intensive
care unit and again these are patients who have
CMV disease either as a result of their renal
disease or following chemotherapy to cancer. So, a
numerous different types of patients who develop
an infection or CMV reactivation in my clinical
practise.

Bob Hollar:

Okay, terrific! I am going to occasionally try to pare it

back what I think I heard you said and sometimes a very
good job of that, but in part because I just want to make
sure that I understand. So, it sounds like the chief
contributors of patients with a significant CMV risk are
either the cancer patients where that additional risk is
coming from the immunosuppression generated by
chemotherapy regimen or in renal patients where they are
actively being immunosuppressed because of a
transplant, is that right?

Dr. Ostermann:

Transplant or a renal disease, so lupus patients for

instance.

Bob Hollar:

Okay.

Dr. Ostermann:

But there are patients with CMV disease post

transplant as opposed to CMV disease post lupus.

Bob Hollar:

Okay. So, do you manage as part of your practice people

that are on dialysis and end-stage renal disease as well?

Dr. Ostermann:

Yes, yes.

Bob Hollar:

Okay. Well first of all could you give me an idea what

that number is, how many patients would you manage at
any given timeframe?

Dr. Ostermann:

I have 85 dialysis patients under my care.

Bob Hollar:

Okay. Are they at any inherently increased risk for CMV

just by the nature of their hemodialysis and the advanced
kidney disease?

Dr. Ostermann:

Yes, they are.

Bob Hollar:

Okay. Could you quantify or least or give me an idea what

level of risk, is it very low? How would you compare it to
the previous risk groups that we just identified, the
immunosuppressed cancer patients or the transplant
patient?

Dr. Ostermann:

It is lower.

Bob Hollar:

Okay.

Dr. Ostermann:

It is lower and until the point that they get a

transplant and then it is high.

Bob Hollar:

Okay, perfect. You mentioned specifically lupus, is it

lupus nephritis then that typically puts them into that?
Do they enter into that sort of renal flow or they sort of a
separate patient group unto themselves that you
addressed separately?

Dr. Ostermann:

I only look after patients with lupus nephritis.

Bob Hollar:

Okay.

Dr. Ostermann:

If it has got lupus without kidney involvement, I

dont get involved. As a nephrologist, I would only
look after and come across patients with lupus
nephritis on immunosuppression so the number of
patients with CMV disease post treatment for lupus
nephritis are all restricted to renal lupus.

Bob Hollar:

Okay, and about how many patients would that represent

doctor in your recurrent practise?

Dr. Ostermann:

With CMV disease or the lupus nephritis?

Bob Hollar:

The lupus nephritis group.

Dr. Ostermann:

I have got about at the moment just under 30 so

29, I think.

Bob Hollar:

Okay, and how would you compare their risk to like the
baseline dialysis patients? Are the posttreatment lupus
patients greater or equivalent risk or low?

Dr. Ostermann:

Higher, yeah higher.

Bob Hollar:

Higher. Twice as much, 10 times as much?

Dr. Ostermann:

Two to 3 times higher.

Bob Hollar:

Thank you, and tell me a bit about the practise at your

institution as far as people on dialysis are getting put on
the kidney transplant waiting list. What percentage of
your total dialysis patients would be on the transplant
waiting list? Would it be all of them or a portion?

Dr. Ostermann:

No, at the moment 45% of our dialysis patients are

necessarily up to 40. Forty are on the transplant
waiting list.

Bob Hollar:

Okay. Would you classify that group as any difference in

terms of their relative risk as far as CMV goes? Are they
the same as all the hemodialysis patients?

Dr. Ostermann:

The risk of CMV disease is the same as the total

group.

Bob Hollar:

Okay.

Dr. Ostermann:

They are otherwise a little bit. So, in particular,

cardiovascularly they are a little bit sweeter and
stronger.

Bob Hollar:

I see.

Dr. Ostermann:

But their risk of CMV disease is the same as the

total population on dialysis.

Bob Hollar:

Okay, and then tell me a little bit about the patients that
you might be treating with that might be enhanced their
elevated CMV risk because of their immunosuppression
from a cancer treatment. I assume that the once that you
see would have either some you would be consulting on
the basis of the renal aspect. Would their disease have to
involve their kidney or would you just be involved in a lot
of those cases just to kind of consult with regards to
kidney function? Explained how work the patient.

Dr. Ostermann:

No, on this case I would look after them simply

because I am also a physician in the critical care
unit, so I look after patients in the intensive care
unit, and so the cancer patients with CMV disease
why I look after are the ones who have severe CMV
disease need to be admitted to the intensive care
unit and then I would look after them independent
of whether they kidneys are effected or not.

Bob Hollar:

I see.

Dr. Ostermann:

Or the other group are the people who have cancer

including hematological malignancy, so leukemia
also, who are in the intensive care unit for a
different reason, who then get chemotherapy in the
ICU and then as a result develop CMV disease or
reactivation.
So, there is 1 group of cancer
patients who need to come to the ICU primarily
because they have gotten CMV disease and that is

their admitting diagnosis and then there is a

different group who come in with something else,
say an infection or pneumonia or something, and
then we do something to them and then they
develop CMV disease as a complication whilst in
the intensive care unit.
Bob Hollar:

I see. Any idea what the proportion between those 2

groups is? Is it mostly the CMV people that kind of come
in with it or it is a?

Dr. Ostermann:

No, we course more so it is probably 2:1. So, more

patients develop CMV reactivation or infection
whilst still with us as opposed to having such bad
CVM infection that they need to come to the
intensive care unit.

Bob Hollar:

So, are there potential indications or the feeling like there

might be a heightened risk for CMV that might be in the
intensive care unit would also include potentially burns
patients? Do you see any?

Dr. Ostermann:

No, we do not look after burns patients.

Bob Hollar:

Okay.

Dr. Ostermann:

So, they go a specialist burns unit.

Bob Hollar:

What about patients that are in a long-term use of the

mechanical ventilator, have you observed the heightened
risk or potential for CMV infection as a result of that
treatment?

Dr. Ostermann:

Sadly, yes we have seen quite a few. They are

quite tricky because we dont quite know what to
do with them, but yes, yes we have.

Bob Hollar:

Since there are so many potential contributors here or

patient groups that might be at CMV risk, I am gonna sort
of try to see if we can kinda narrow this down to what you
think the patients at highest risk are. So, if you dont
mind I am gonna kinda echo back some of what you told
me...

Dr. Ostermann:

Sure.

Bob Hollar:

And maybe you kinda clarify if I have it correct and if I do

perhaps what the biggest current risk groups I should say.
So, we have the kind of baseline I will call it the dialysis
patients that you are currently treating and then above
and beyond that we have also the posttreatment lupus
nephritis patients that, as I recall, you mentioned, are at
somewhat higher risk than the base patients.
We also
have the transplant list that those really arent
differentiated from the sort of larger group of
hemodialysis patients right?

Dr. Ostermann:

The transplant patients have the higher risk.

Bob Hollar:

Okay.

Dr. Ostermann:

But only when they have received the transplant,

not when they go on the transplant waiting list.

Bob Hollar:

Yes, they are.

Dr. Ostermann:

When they are on the waiting list, the risk is the

same but as soon as the moment they get a
transplant, then they are at the increased risk.

Bob Hollar:

Okay.

Dr. Ostermann:

Whilst waiting on the waiting list and receiving

dialysis, the risk is the same as the normal dialysis
population.

Bob Hollar:

And then you also mentioned that the cancer patients

who are receiving because of the nature of their cancer
treatment are actually at an increased risk for CMV and
then we also have the posttransplant patients who are at
much higher risk for CMV, I assume.

Dr. Ostermann:

Thats right.

Bob Hollar:

And then we also talked about the ventilator patients

which seem to be the contributor and you also mentioned
the hematological cancer. So, I dont want us to get too
bogged down because I want to go into a little bit of detail
about the individual, the characteristics of each one of
those individual patients. So, I want to kinda narrow it
down to the things that you think are sort of the highestrisk groups out of those. So could you help me out with
that?

Dr. Ostermann:

The highest-risk group?

Bob Hollar:

Well, groups you know. My guess is that the solid organ

transplant, the kidney transplant are amongst the highest,
but could you help me out from that point on down?

Dr. Ostermann:

Yeah, so youre right they are the highest group. In

particular, since we increasingly do complex and
higher risk transplant procedures. So these are
patients who are immunologically at high risk and
as a result need extra immunosuppression and
more heavy immunosuppression, they are at very
high risk, and then following on from that I would
say the cancer patients, people who have received
chemotherapy
for
active
malignancies,
in
particular, the hematological cancers, and that is
because the hematological cancers are leukemia
and so they get treated quite aggressively during
the acute phase. So, the risk of CMV disease is
directly
proportional
to
the
burden
of
immunosuppression.

Bob Hollar:

And beyond the sort of we have the complex high-risk

transplant and then I would assume we have the more
uncomplicated less high-risk solid organ transplant, and
then below that, we have the immunosuppresed cancer
patients and then hematological cancers or

Dr. Ostermann:

Yeah, yeah that make sense and then we would

have
the
renal
patients
who
receive
immunosuppression for renal disease, so lupus for
instance, lupus nephritis patients.

Bob Hollar:

So, for now, what I am gonna do is sort of exclude the

standard transplants because I think we probably have
looked at that, but I am in particular interested in the
other cases that you mentioned. So, can I ask you about
each one of those briefly?

Dr. Ostermann:

Okay.

Bob Hollar:

First of all, could you give me an idea what your typical

zero prevalence of CMV is? What percentage of your
patients in general is CMV positive?

Dr. Ostermann:

About 60%. I mean almost 65.

Bob Hollar:

And so for each one of these groups, could you give me

an idea that, well lets start out with the highest risk
group and the very high-risk transplants; would this be
because of the immunological complications where they
would necessitate like an induction therapy kind of
regimen or is there something beyond that?

Dr. Ostermann:

It
is
the
burden
or
this
intensity
immunosuppression right in the beginning.

Bob Hollar:

So, they are on aggressive regimen or dosage than your

standard patients under the consequence or more than
those?

Dr. Ostermann:

Yes, correct.

Bob Hollar:

Okay, and so how often, well tell me how you manage

CMV for those patients. Do you monitor them or do you
prophylax them? What would typically be done?

Dr. Ostermann:

So, we prophylax patients who are CMV negative

but receive a CMV-positive kidney.

Bob Hollar:

Okay.

Dr. Ostermann:

This group gets receives prophylaxis for 3 months.

Bob Hollar:

Okay.

Dr. Ostermann:

All the others get monitored once a week. So, the

CMV positive receiving a positive kidney or the
CMV negative was receiving a negative kidney get
monitored every week.

Bob Hollar:

So, I am sorry did I hear that you even monitor the minusminus patients?

Dr. Ostermann:

We do, yeah we do.

Bob Hollar:

And you could you break down how often you might
expect to see? Do you see any significant incidence of
disease in any of those groups?

Dr. Ostermann:

So, we see a disease in the CMV positive ones

receiving a negative kidney and it is usually a
reactivation. Yeah, we see quite of

of

Bob Hollar:

Percent of total patients? How manywhat would you

estimate your overall incidence of CMV disease would be?

Dr. Ostermann:

You mean, percentage. Do you mean of the whole

CMV group or to people, what is your denominator?

Bob Hollar:

Whichever you are more comfortable answering either

what percentage of the high-risk group is likely to contract
CMV disease or of the transplant patients as a whole?

Dr. Ostermann:

If you use CMV-positive patients receiving a

negative kidney, if you use this as your
denominator, then about 10-15% of patients
reactivate.

Bob Hollar:

Okay.
Now tell me more in the case of
immunosuppressed cancer. This is typically patients
have received such extent the chemotherapy
radiation therapy in that their immune systems
depleted is that right?

Dr. Ostermann:

Thats right.

Bob Hollar:

Okay. How often would you expect to see CMV infection

or disease in that patient group?

Dr. Ostermann:

So, usually if they are CMV positive, then we see a

reactivation about 25-30%.

Bob Hollar:

Now, when you were talking about this group, is that

including the hematological cancers or is this a separate
group?

Dr. Ostermann:

I have included them, yeah, yes.

Bob Hollar:

Okay, okay. So, would you consider the thyroid tumor

patients that have been on a long term kind of regimen
that has impacted their immune system, are they at the
same level of risk as the hematological cancers might be
or people that are likely to receive a stem cell transplant?

Dr. Ostermann:

So, the hematological ones have a highest risk of

reactivation because they get more intense
chemotherapy and their risk is somewhere 40-45%.

Bob Hollar:

And just out of curiosity, what would you consider the

relative risk for the lupus patient?

the
who
and
are

Dr. Ostermann:

That is significantly. So, the CMV-positive lupus

patients, the risk of CMV is, it depends a little bit
on the degree and intensity of immunosuppression
they have received but the standard patient only
has a risk of 5-10%.

Bob Hollar:

Okay. That is very helpful. They kind of sort of establish

what the risks here are. Now, how many of these patient
groups would be?
I know you already clarified the
situation with regards to the organ transplant, but
amongst the rest, between the cancer patients and the,
perhaps, even the lupus patients, how often do you test or
do you at any time actively kind of monitor these patients
for CMV status?

Dr. Ostermann:

How do we monitor?

Bob Hollar:

Yeah, monitor them at all. Do you just monitor them

symptomatically or do you sort of regularly check their
viral load as you would with the transplant?

Dr. Ostermann:

No, we dont monitor them, we wait for symptoms.

So, if they have a fever or an unexplained fever or
some new changes on x-ray so then we would
check but we would not routinely monitor, no.

Bob Hollar:

Okay, and when these symptoms did show up, would that
be the next step as to do a blood test?

Dr. Ostermann:

Yes, thats right.

Bob Hollar:

And would that be verified through PCR?

methodology is?

Dr. Ostermann:

PCR, yes.

Bob Hollar:

Okay, and what would you look for in that test result to
base your decision upon further action? What kind of PCR
result would trigger a response?

Dr. Ostermann:

So, we measure PCR then we measure the viral

load, and as soon as it is positive, it certainly
triggers a response.
The response may not
necessarily be treatment but, it would be, the
response is alertness. If the level is low, we would
repeat it again and if the level was high and the

Is that the

symptoms fitted in the right patient, we would

initiate treatment.
Bob Hollar:

Okay.

Dr. Ostermann:

So, if it is positive with a low viral load, we may just

repeat it again and wait a bit longer and also
consider
or
explore
whether
the
immunosuppression can be reduced a bit.

Bob Hollar:

I see. Is there a guideline as far as an exact threshold of

number of copies or something along those lines that you
might say, well somebody over 5000 is going to get
treatment, or is it all individualized by the overall patient?

Dr. Ostermann:

There is a guideline for the management of CMV

post transplant, and yeah we often use this
guideline also for the management of patients with
CMV post lupus but we dont have a guideline for
the management of patients in the intensive care
unit,
so
patient
with
CMV
disease
post
chemotherapy; that is a bit more individualized,
patient-by-patient decisions.

Bob Hollar:

Okay. Tell me would there be any circumstances in which

you try to sort of pre-assess or use patient risk factors to
kind of change the way that you manage particular
patients for CMV? Are there patients that might be at
such high risk that you would in some way treat them
differently so as to take greater care to avoid infection or
something like that? The thing that I was thinking about
was the immunosuppression you mentioned that there are
some
patients
that
are
very
aggressively
immunosuppressed.
Are there other kinds of either
therapy or comorbidities that would in you mind really
elevate a patients CMV risk?

Dr. Ostermann:

Not really. We dont do any other risk assessment

apart from checking their CMV status in transplant
patient. If it is negative and they have received a
positive kidney, we will initiate prophylaxis but that
is the only type of risk assessment we do.

Bob Hollar:

Okay.

Dr. Ostermann:

So, we identify the high-risk patient and we think

the person who is negative receiving a positive
kidney has the highest risk, but we dont do any
other risk assessment.

Bob Hollar:

For instance, in your ICU experience, when you treat

cancer patients, is their CMV status automatically known?
Is that something that is tested?

Dr. Ostermann:

No, not necessarily, no.

Bob Hollar:

Okay.

Dr. Ostermann:

It may be known, it maybe available but it is rarely

available so not routinely.

Bob Hollar:

So, if I understand correctly then most of those cases they

are not actively managed that if a patient presents with
symptoms that cause you to be suspicious that they may
have a CMV infection, then at that point, you would do
PCR testing and other followup therapy as warranted, is
that right?

Dr. Ostermann:

Correct.

Bob Hollar:

What about the ventilator use, is that something where

the patient is, is there exposure or potential risk to CMV
proportional to basically their exposure to the ventilator
by the time that they are out of this? I am looking for any
other factors that might sort of help stratify what these
patient risk populations are. So, would time on the
ventilator be a possibility?

Dr. Ostermann:

Yes it is, time on the ventilator, mainly because it

correlates with underlying illness and often with bit
of immunosuppression during their stay in ICU. So,
we give hydrocortisone to people with severe
sepsis and these are exactly the patients who may
need to stay in the ICU for longer recovering from
their illness. This other group is the people with
ALDS. Again, they occasionally get treated with
steroids for their ALDS, and these are exactly the
people who also spend a longer time on the
ventilator and therefore it is the time on the
ventilator plus the fact that this time on the

ventilator
may
have
immunosuppression.

been

associated

with

Bob Hollar:

You just sort of triggered another possibility. Is it just the

amount of time that they spend in the ICU, is that another
potential?

Dr. Ostermann:

Yes, it is also. Yes, definitely so. A longer stay in

the ICU usually means that patients were sicker so
it correlates with severity of illness.
It also
correlates with a reduced immunity, so people who
spend a long time in the ICU entirely become more
immunosuppressed as a result of weakness, critical
illness.

Bob Hollar:

I see. So, is it fair to say then that the amount of

exposure that they have basically to just the ICU is
proportional, I mean as soon patients arrive in the ICU do
they basically become at certain level of risk and that sort
of proportionally increases as their stay extends or is
this..? I probably not asking that question.

Dr. Ostermann:

Yeah. I mean the risk is high in the beginning when

they are very sick.

Bob Hollar:

I see.

Dr. Ostermann:

It is we then add immunosuppression or

chemotherapy, then the risk increases further, and
then as patients get better, their risk reduces a bit
because it is not quite as high as during the acute
phase, but as patients stay in the ICU for a long
time, then gradually it goes up again.

Bob Hollar:

Is it possible that you can sort of, are there any trends
with regards to when you might see CMV incidence in
terms of when during their stay in the ICU so you see
some infections or disease immediately or does it
basically just increase gradually over time?

[PHONE RINGING]
Dr. Ostermann:

Can I just interrupt you.

phone a second?

Bob Hollar:

Sure.

Can I just answer this

[ANSWERING PHONE]
Bob Hollar:

So, when if patients are going to evidence a CMV

infection, is there a particular time during their stay in the
ICU when you might typically be more likely to see that?
When they first get there

Dr. Ostermann:

Not really, no there is no typical pattern, I think.

Bob Hollar:

Okay.

Dr. Ostermann:

I mean that is why patients are all very different.

Bob Hollar:

How significant are the consequences of CMV disease in

the environment that we are talking about here? If you
are in the ICU, I mean, just give me an idea of the
magnitude and what the consequences of that disease
might be?

Dr. Ostermann:

If they truly have CMV disease in the intensive care

unit, they have a significant increase in their risk of
dying. So, if CMV disease occurs in somebody who
is very ill in the intensive care unit to start with,
then sadly it increases the risk of needing more
organ support so they may need more help from
the ventilator, they may need drugs to support the
heart, and they also needs medication and the
medication of ganciclovir is effective but has
serious side effects especially side effects on the
bone marrow, and so CMV disease has serious
consequences and could kill people.

Bob Hollar:

Okay.

Dr. Ostermann:

Especially, these are obviously people vulnerable to

start with.

Bob Hollar:

Sure. There are few other metrics I just want to sort of

read them off here to see if it triggers anything in terms of
your experience. Infirm, quantitate if you can. What
about the occurrence of other complications ?

Dr. Ostermann:

Yeah, definitely. So, CMV disease can effect the

lungs and can effect the gut or the lining of the
stomach. It can cause serious bleeding from the
stomach or from the gut. Yeah, definitely.

Bob Hollar:

What about impact on days of stay, does that have a..?

Dr. Ostermann:

Oh yeah, yeah, people who get CMV disease sits

some back and they spend extra days in the
intensive care unit.

Bob Hollar:

Any guesses on what the order of magnitude of that?

Dr. Ostermann:

No, that is difficult to stay.

Bob Hollar:

Okay.

Dr. Ostermann:

Although you are talking days, several days, not

just 1 day, several days.

Bob Hollar:

And you mentioned the added medication burden that

typically would be, the antiviral for treatment in the ICU
setting would be ganciclovir, did I understand that right?

Dr. Ostermann:

Correct, yeah, yes.

Bob Hollar:

Okay.

Dr. Ostermann:

And ganciclovir requires a central line so they need

an extra catheter in one of the bigger veins to put
this catheter in their wrists so it may have
complications, and then the treatment is at least
10-day course of ganciclovir and ganciclovir is
effective but can suppress the bone marrow.

Bob Hollar:

I realized that doctors are typically above the cost aspects

of disease but the reality is in many cases I think you are
still asked to kind of at least consider that. As a result of
that, is there any way that you could make an assessment
of what the cost of the CMV complication might be if you
diagnosed the patient as having CMV disease during their
stay in the ICU? Would you hassle to guess as to what the
incremental cost if that patient ends up requiring as the
result of that infection?

Dr. Ostermann:

You mean financial cost presumably?

Bob Hollar:

Yes.

Dr. Ostermann:

So, a day in the intensive care unit in the UK costs

1600 pounds and CMV definitely increases the
length of stay by several days, say 5, 6, 7,
sometimes more. Say an average of 5. So, that is

10,000 pounds and in between if they have a

complication they may need extra intervention so
the person who gets a GI bleed from CMV colitis,
may need an endoscopy but may also need
interventional radiology and all this increases the
cost further.
Bob Hollar:

Sure. Thats terrific. Thank you doctor, that is really

helpful. So, to clarify when, I am going to focus, I really
think that the information about the ICU patients because
you do see quite a cross section of them and your
experience their sounds like, so I am going to kind of
focus on that for some of the subsequent question, and
did mention that typically you dont know the CMV zerostatus of those patients in the ICU. You might but it is not
routinely available and so you would not necessarily
stratify, you wouldnt change anything in their treatment
based upon their serological CMV status because you
typically would not be aware of that right?

Dr. Ostermann:

Corect, yeah correct.

Bob Hollar:

Okay.
Once they become infected and have been
diagnosed, do you then monitor their CMV load
subsequently during treatment? How is that?

Dr. Ostermann:

Yeah.

Bob Hollar:

And how often or for how long would you typically do

that?

Dr. Ostermann:

So, we monitor them weekly. So, if they have had a

positive result and a positive viral count, so the
person with the positive count and who will start
treatment, a 10-day course of ganciclovir, will be
monitored weekly.

Bob Hollar:

Okay.

Dr. Ostermann:

But the person who has a positive count and it is

still low but positive and the decision is made not
to start treatment, then they will have a repeat
test 2-3 days later.

Bob Hollar:

Okay.

Dr. Ostermann:

So, whilst weekly is not treatment but positive,

then every 2-3 days.

Bob Hollar:

Okay. Let me just get down here. So, you typically would
not be aware necessarily of any subclinical infection of
CMV that might be sort of testing prior to producing any
sort of clinical symptoms, right so..?

Dr. Ostermann:

Not really, no.

Bob Hollar:

Is that a concern to you or do you worry about those kind

of subclinical infections in the setting that you are up
running?

Dr. Ostermann:

Yeah, I do because occasionally we have patients

who deteriorate a bit and who in a nonspecific way
and their x-ray gets a bit worse and then we screen
for lots of things including CMV and then we find
they have got pneumonia from an ordinary bug, but
at the same time they are also CMV positive, so you
are not sure whether the deterioration is due to
CMV or whether it is due to another infection.

Bob Hollar:

I see.

Dr. Ostermann:

And you, in this case it is difficult to interpret the

CMV result because it may just be a bit of
reactivation in the context in somebody who has
become ill.

Bob Hollar:

I see.

Dr. Ostermann:

Or it may be the beginning of serious CMV infection

and requiring the treatment but only want to give
the treatment of the say the ganciclovir to people
who really need it and not the people who have just
reactivated but it is not causing any problems yet.

Bob Hollar:

Sure, okay I understand. Have you or your institution

changed anything in the last few years with regards to
how you manage CMV or the risk for CMV?

Dr. Ostermann:

Not in the last few years but about 10 years ago we

changed the prophylaxis to valaciclovir.

Bob Hollar:

To valaciclovir?

Dr. Ostermann:

Sorry, valganciclovir.

Bob Hollar:

Okay, very good. So, again sort of focusing in an ICU

aspect of your experience right now, how satisfied are you
with the tools that you currently have at your disposal to
manage and treat CMV?

Dr. Ostermann:

Not very satisfied because what we dont know is

whether we dont know the meaning of a slightly
positive result. What we dont know is whether it
is just a marker of illness so that the patients have
reactivated and it is because if they are very sick or
whether it is a serious disease contributing their
illness and needs treatment, so we dont know who
to treat and who not to treat.

Bob Hollar:

So, I am trying to think about in you mind what could be

done to improve that, does it need a better screening
technologies or I mean would a vaccine or some other
kinds of preventative measure offer an improvement that
would address some of the concerns that you have?

Dr. Ostermann:

I dont think a vaccine would help here because we

are talking about the patient who has returned
positive, and that is when we face its dilemma.
What would either better test to differentiate
active infection from reactivation, so better
diagnostic tools, or more clinical trials showing that
active treatment with whatever drug, ganciclovir or
valganciclovir to people who are even if their viral
count is low is helpful.

Bob Hollar:

Okay. Do want to ask you know about the sort of the

concept of prevention strategies or proactive CMV
management strategy. So, you mentioned that you did
not think a vaccine would be helpful.

Dr. Ostermann:

Not in the intensive care setting by the time

somebody is positive, no.

Bob Hollar:

Okay.

Dr. Ostermann:

Clearly, before yes. If you want to reduce the

number who may turn positive, clearly a vaccine
may help, yes.

Bob Hollar:

What if the vaccine would help people that were CMV

positive as well though, what if there was demonstrated

efficacy with regards to the ability to either enhance or

produce a better immune response to that, the late
infections, so as to suppress any reactivation, would that
change your opinion of the utility of that tool to manage
CMV proactively?
Dr. Ostermann:

Yes, that would be very good yeah. If a vaccine to

boost as you described the reactivity to CMV virus
could help, that would be very good.

Bob Hollar:

Okay. Well let us talk about this

Dr. Ostermann:

I mean the vaccine would be of highest use to

people who are CMV negative as to that aspect.

Bob Hollar:

Okay, sure.

Dr. Ostermann:

And they would have to be vaccinated before they

are exposed to horrible immunosuppression, so
before they receive the transplant, before they
receive chemotherapy.
But if the vaccine also
helped to boost immunity in people who are
positive, then yes that would be very useful.

Bob Hollar:

Well, let me ask you about that the necessity to

vaccinate prior to immunosuppression, is that based on
your presumption that no vaccine could mount or that a
vaccine simply would not work if someone who is severely
immunosuppressed, does that..?

Dr. Ostermann:

No, it is based on the assumption that any patient

receiving
a
transplant
will
heavy
immunosuppression and it would be during this
time of heavy immunosuppression that is when
they are most vulnerable. So, it would be useful to
have adequate antibody load onboard at that time.

Bob Hollar:

Okay.

Dr. Ostermann:

In order to have produced the antibodies you would

have to I assume you have to give the vaccine
before.

Bob Hollar:

Okay, you know I want to talk to you about that after we

kind of go through a little bit of the particular vaccine that
they are developing, but I want to ask you about as an
optimum strategy you would want to have people

basically vaccinated well in advance in order for them to

be well immunized by the time that you might see them
in the ICU, is that daily?
Dr. Ostermann:

Yeah, some time.

Bob Hollar:

Correctly?

Dr. Ostermann:

Correct.

Bob Hollar:

So, doctor did you receive the discussion guide and the
materials that were sent in advance by email by any
chance?

Dr. Ostermann:

Yes, I did.

Bob Hollar:

In the middle there is a short description, a vaccine

description, just after New Team and I wonder if you might
look it over and we could go over that briefly and answer
any questions and I would just like to ask you about your
reaction to a product like that.

[PAUSE]
Dr. Ostermann:

Yeah, it looks good.

Bob Hollar:

So, overall do you see, I realize this is arbitrary but in a

scale of 1 to 5, what would be your reaction to a product
like this or some of the very patient applications that we
just talked about.

Dr. Ostermann:

5.

Bob Hollar:

Okay. How does that [clears throat] pardon me, the 40%
reduction in CMV disease or viremia, how does that stick
with your expertise? Okay?

Dr. Ostermann:

It is very good, it is good.

Bob Hollar:

What about the dosing schedule, there it shown as 5

injections over 6 months, how does that stick with the
duration of your interaction with patients? My guess is
that most patients are in ICU that long.

Dr. Ostermann:

So, this is a vaccine which is in this case targeted

at transplant patients so not be ICU

Bob Hollar:

It was originally, but what we really want to investigate is

in addition to that, what other possible potential

applications might exist and so obviously the reason I am

asking you a lot of that questions about the ICU is
because I think like that is where a lot of the patients that
develop CMV complications end up getting collectively
identical. I am trying to find out beyond the clearer
benefits of something like this might have at found in
organ transplant environment. What about some of the
cancer patient, other renal patients that also might be
immunosuppressed or obviously very ill in the ICU, would
any of them benefit from a product like this? Is there a
way that this could be administered to where it would
offer them some protection?
Dr. Ostermann:

If the vaccine works in patients who are

immunosuppressed receiving chemotherapy, then it
may have a role but clearly to wait for 6 months to
require 5 injections over 6 month means you
presumably it takes a couple of some time before
the antibodies are produced, now that is unrealistic
for people with newly diagnosed cancer. So, if I
have cancer now diagnosed today and needed
chemotherapy now, then I would not want to wait
for 6 month, I would want my chemotherapy to
start as soon as possible. But clearly if I could
have my chemotherapy and I could have the
vaccine and the vaccine was still working despite
chemotherapy on board, then I would have it
because
although
it
ma
not
protect
me
immediately, hopefully, it will protect me for my
second or third course of chemotherapy.

Bob Hollar:

I hate to hop around on you doctor, I am sorry. I am

running just a little bit long. Could you indulge me for a
few more minutes just to wrap a few more things?

Dr. Ostermann:

Sure.

Bob Hollar:

A couple of pages past where we were, there is a short

description of another product which they are considering,
and this is a monoclonal antibody against CMV, sort of
same line of that side again and was wondering if how
you might see a product like that which might confirm
more immediate immune benefit to be used as sort of a
short-term strategy and the vaccine being more of a long-

term strategy towards conferring immediately, would you

see any value to that approach?
Dr. Ostermann:

Definitely. So, a medication which is for the acute

setting so enhancing the antiviral activity of
ganciclovir so boosting the therapy would be very
good, because
not everybody responds to
ganciclovir
and
sometimes
people
get
complications from CMV disease before the
ganciclovir has an effect. So, if you could prevent
that, that will be very good.

Bob Hollar:

Well let us talk though for a moment about the situation

that you mentioned where some newly diagnosed with
cancer and based with you know very aggressive and
debilitating potentially chemotherapy regimen, is that a
patient that you might immediately treat with this kind of
immunoglobin to minimize the sort of upfront risk and
then also start on the CMV vaccine to sort of confer a
longer term protection, I mean would there be a net
benefit to patients? Would you consider doing that given
what the level of risk is to patients at that point?

Dr. Ostermann:

I would not do that, no, not based on what I am

reading here. So, based on what I am reading
here, here is an antibody which is given as an
adjunct to ganciclovir in order to whilst treating
active CMV infection so I would only give this
antibody in the setting of confirmed CMV infection
treated with ganciclovir.

Bob Hollar:

You would not under any circumstances use this as a

prophylactic agent?

Dr. Ostermann:

Not based on what is in this paragraph.

there is different info and then I would not.

Bob Hollar:

Okay. Going back to the vaccine doctor, the 5 injection

schedules over 6 months, you had mentioned that, does
that seem onerous. Would this be a drawback to you?

Dr. Ostermann:

Not really know, no, it is 5 injections but renal

patients,
in
nephrology
most
patients
are
vaccinated against hepatitis B and that is at least 3
injections so 2 more injections for high-risk group
is not unusual and it is not too difficult.

Unless

Bob Hollar:

Okay.
Is there anything that would prevent you or
dissuade you from using a vaccine like this? What would
be the things that you would need to satisfy yourself of
prior to use?

Dr. Ostermann:

The safety profile and I would want to see the

clinical data so the number of patients enrolled.
So, you said it was prevented in 40, so it says 40%
reduction, I dont know what reduction means,
does it mean complete prevention or does it mean
reduction in severity? I would want to see the
exact clinical data before using it.

Bob Hollar:

Yes of course. Just for the record, I think it was a

reduction in incidence so there is 40% patients actually
contracted disease.

Dr. Ostermann:

Okay, that is good.

Bob Hollar:

So, tell me how this might impact your practice? How

might assuming these reservations or things that are
uncertainties right now resolve, how might you use some
product like this? Where would you see at setting?

Dr. Ostermann:

Are we talking about renal practice or critical care

practice?

Bob Hollar:

You know what, where you see if there is a fit in both

place, would that appreciate you kind of think each?

Dr. Ostermann:

Okay, so think the most suitable role is dialysis

patients who are going on the transplant waiting
list and who have an increased risk of CMV, so highrisk dialysis patients pre-transplantation. I think
they would be suitable for a vaccine and takes the
waiting list in the UK for transplant is longer than a
year so 6 months of regular injections would be
fine.

Bob Hollar:

Do you see any applicability beyond that particular

application?

Dr. Ostermann:

If you said the vaccine also works in people actively

receiving immunosuppreesion, then I could also see
a
role
in
patients
who
are
receiving
immunosuppresion for other condition first; for
instance; lupus and I could see a role for people

who for some 1 reason or another receive a

transplant without having had the vaccine before.
So, if a high-risk patient received the transplant
but has not had the vaccine before and you pay to
confirm that the vaccine Is compatible with
immunosuppresion then I could see it being used at
time of transplantation.
Bob Hollar:

Okay, very good.

Doctor is there anything and I
appreciate you being so indulge about the time but I am
going to wrap it up right now and just ask you if there is
any thing that comes to mind that we did not discuss and
I did not ask you about at least that you think is relevant
to the topics we hit on today?

Dr. Ostermann:

No not really,
questions.

Bob Hollar:

Is there might you suggest, anyone that would be really

good for us to talk to that has a broad, sort of base and a
lot of disease indications to a potential CMV risk, are
there?

Dr. Ostermann:

The HIV doctors, so doctors specialized in HIV

disease.

Bob Hollar:

I s there somebody that you think of that would be

somebody in particular that we should talk to?

Dr. Ostermann:

I cant think of anybody but I think any doctor who

specializes in looking after patients with retroviral
disease is fearful of CMV disease, especially if it
effects the eyes and people get blind.

Bob Hollar:

Okay. Doctor you have been very pleasant to talk to and

very informative so I appreciate that very much. I am
going to have my colleague forward on an email to you
that kind of confirms our talk today and also introduce
some further details about your honorarium. There is also
going to be a link in that email. I wonder if I could impose
upon you enough to just click on that and there a short,
maybe 3- or 5-minute online survey that is going to ask
you to just quantitatively rate a few items and if this goes
so much after kind of clicking on things online, then it
would for me to verbally poll you on that. So, if you will
be kind enough to do that, we will get your honoraria on

think

you

have

asked

those

its way to you as soon as we get a feedback from that and

you should be good to go. I really enjoyed our talk today
and I think we got some valuable information and I want
to wish you a good rest of your day and thank you for
your participation.
Dr. Ostermann:

Okay, it was my pleasure.

Bob Hollar:

All right, thank you doctor?

Dr. Ostermann:

Okay, thank you ba-bye!

T: BCM
D: 03/16/13