Developing Rabies Monoclonal Antibody Products as a Component of Rabies Post-exposure ...

328 Pages·2017·0.76 MB·English

by  Capital Reporting Company

Monoclonal Antibody Product Development for Rabies
Post-exposure Prophylaxi – July 17, 2017

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3 MONOCLONAL ANTIBODY PRODUCT DEVELOPMENT FOR RABIES
4 POST-EXPOSURE PROPHYLAXIS
5 Monday, July 17, 2018
6 8:30 a.m.
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9 FDA
10 10903 New Hampshire Ave, Bldg. 31
11 Silver Spring, MD, 20903
12 [phone]
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19 Reported by: Samuel Honig
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Monoclonal Antibody Product Development for Rabies
Post-exposure Prophylaxi – July 17, 2017

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1 A P P E A R A N C E S
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3 ED COX
4 SARAH CONNELLY
5 LOUISE TAYLOR
6 DOROTHY SCOTT
7 HENRY WILDE
8 ERIN GRACE SPARROW
9 BEATRIZ QUIAMBAO
10 JAMES A. ELLISON
11 SUSAN MOORE
12 DAMON DEMING
13 CHRISTINE FEHLNER-GARDINER
14 TANVIR BELL
15 HOLLY TAYLOR
16 GEORGE SIBERRY
17 JESSE BLANTON
18 RICHARD FRANKA
19 DEBORAH MOLRINE
20 BHAGWAT GUNALE
21 CATHERINE BROWN
22 THOMAS FLEMING
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Monoclonal Antibody Product Development for Rabies
Post-exposure Prophylaxi – July 17, 2017

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1 A P P E A R A N C E S (cont’d)
2 GEETHA SRINIVAS
3 ROBIN LEVIS
4 SKIP NELSON
5 THAMBAN VALAPPIL
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7 C O N T E N T S
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9 ED COX 5
10 SARAH CONNELLY 10
11 LOUISE TAYLOR 24
12 DOROTHY SCOTT 43
13 HENRY WILDE 55
14 ERIN GRACE SPARROW 74
15 BHAGWAT GUNALE 98
16 BEATRIZ QUIAMBAO 110
17 DAMON DEMING 120
18 JAMES A. ELLISON 121
19 SUSAN MOORE 129
20 CHRISTINE FEHLNER-GARDINER 145
21 DEBORAH MOLRINE 147
22 RICHARD FRANKA 153
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Monoclonal Antibody Product Development for Rabies
Post-exposure Prophylaxi – July 17, 2017

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1 JESSE BLANTON 157
2 SKIP NELSON 158
3 ROBIN LEVIS 162
4 GEETHA SRINIVAS 165
5 TANVIR BELL 167
6 GEORGE SIBERRY 170
7 CATHERINE BROWN 176
8 THOMAS FLEMING 182
9 THAMBAN VALAPPIL 209
10 HOLLY TAYLOR 223
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Monoclonal Antibody Product Development for Rabies
Post-exposure Prophylaxi – July 17, 2017

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1 P R O C E E D I N G S
2 DR. COX: First of all, I wanted to just
3 welcome everybody today to -- joining us for our
4 workshop on developing rabies monoclonal antibody
5 products as a component of rabies post-exposure
6 prophylaxis. And just to start out with some nuts
7 and bolts, important issues, as far as lunch, I've
8 been told to let you know that there's a kiosk
9 that's right across from the registration desk and
10 if you -- you know, over the course of the morning
11 and -- Sunita, how soon should they go out to
12 order? So, any time this morning, but probably,
13 you know, by the break. If you order your lunch
14 at the kiosk, that will prevent some of the delays
15 that can happen when everybody sort of descends on
16 the window out there to get lunch. So, just want
17 to take care of that nuts and bolts issue, it's
18 important. And I think, you know, over the course
19 of the day, we'll hear a number of important talks
20 about the epidemiology of rabies, we'll hear some
21 about prior approvals for H (Inaudible) rabies
22 immunoglobulin, the type of evidence that was
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Monoclonal Antibody Product Development for Rabies
Post-exposure Prophylaxi – July 17, 2017

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1 available, what can be learned from pre-clinical
2 and some of the available clinical data from
3 previous products that have been studied for
4 treatment of prophylaxis, I should say prophylaxis
5 of rabies. And as we'll discuss today, developing
6 a new monoclonal antibody for post-exposure
7 prophylaxis of rabies carries with it a number of
8 challenges, and we found workshops as these to be
9 particularly helpful as we work through
10 challenging areas of drug development and clinical
11 evaluation of products. And there are certain
12 characteristics, if we reflect upon rabies, you
13 know, what makes this difficult? Why is this
14 challenging? And it is interesting, if you look
15 across other areas that are difficult and
16 challenging, and this may be even more challenging
17 than some others, there are certain
18 characteristics of the disease and the available
19 therapies that make this difficult. There's a
20 tremendous urgency to initiate treatment, in this
21 case, early post-exposure prophylaxis, in the
22 setting of a suspected case. And for each
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Monoclonal Antibody Product Development for Rabies
Post-exposure Prophylaxi – July 17, 2017

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1 individual case, there's a degree of uncertainty
2 as to the level of risk for the particular
3 exposure, but you know, with rabies you need to
4 err on the side of treatment to avoid missing an
5 opportunity to administer a lifesaving post-
6 exposure prophylaxis regimen. The available
7 preventative measures work quite well, in -- you
8 know, for many, so we don't want to lose efficacy,
9 given, you know, the consequences of a reduction
10 in efficacy for a disease such as rabies, then
11 there really is no realistic opportunity for
12 rescue therapy. You know, what needs to happen
13 needs to be effective and needs to be given
14 urgently. And also, making this challenging, too,
15 that the regimen is really -- there are multiple
16 components, each of which adds something to
17 treatment or to post-exposure prophylaxis. You'll
18 probably catch me saying that over the course of
19 the day, treatment, when I really do, in fact,
20 mean post-exposure prophylaxis, which makes it
21 difficult to quantitate the contribution of each
22 of the different components, you know, overall in
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Monoclonal Antibody Product Development for Rabies
Post-exposure Prophylaxi – July 17, 2017

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1 the treatment regimen. And I'm sure as the day
2 goes on, I'll learn more and we'll talk about
3 other factors that we need to think about in
4 developing and characterizing a new product for
5 post-exposure prophylaxis for rabies. As part of
6 our discussions, too, it will be important, as we
7 work through each of the different components,
8 what can be done to think about the value and
9 limitations of the information that can be gained,
10 and if there are limitations, is there additional
11 information or research that could help to close
12 some of these gaps? A question that we'll talk
13 about, I'm sure, is how much evidence is needed
14 before relying upon a new monoclonal antibody for
15 post-exposure prophylaxis as part of an overall
16 regimen? How much do we need to know? What level
17 of evidence do you need to have before relying
18 upon it in people who've been exposed? We should
19 also keep in mind that there are risks that make
20 one nervous as you think about a clinical trial.
21 You know, what are the -- you know, what are the
22 reasons that, you know, there's trepidation when
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Monoclonal Antibody Product Development for Rabies
Post-exposure Prophylaxi – July 17, 2017

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1 entering into a clinical trial. And if you
2 reflect on that for a moment longer, you see that,
3 in fact, the clinical trial is probably the most
4 controlled setting. So, those -- although those
5 trepidations and nervousness may be somewhat more
6 removed, they are only amplified in the setting of
7 use outside of a monitored setting, such as a
8 controlled clinical trial. So, I hope and expect
9 that we'll find that the type of information that
10 we, as regulators, want is really the same type of
11 information that scientists and patients and we
12 all -- and clinicians, essentially, which we all
13 are, too, I think we all sort of overlap in our
14 disciplines and our perspectives, it's really all
15 the same information. And that really is, you
16 know, will the product be effective in post-
17 exposure prophylaxis for patients exposed to
18 rabies? So, we'll work towards, you know,
19 understanding what information can be gleaned, the
20 limitations of that information, and what
21 additional work might help to further close the
22 gaps out there in knowledge. For diseases like
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Monoclonal Antibody Product Development for Rabies
Post-exposure Prophylaxi – July 17, 2017

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1 this, they are particularly challenging.
2 Oftentimes, those challenges and frustrations
3 really arise from the biology of the disease and
4 the limitations of our knowledge. So, we'll
5 continue to persevere and work through it and get
6 to some answers, solutions, and identify the
7 limitations of what we do know. So, with that, I
8 want to -- and one other thing, too, on that same
9 theme, is that we really can't change the biology
10 of rabies disease, at least not yet. So, really,
11 our position is one of trying to understand it
12 best, so that we can study it well. So, I look
13 forward to today's discussions and towards our
14 shared goal of figuring out our approaches for the
15 development, evaluation of new monoclonal antibody
16 products as a component of rabies post-exposure
17 prophylaxis to meet patient needs that are out
18 there. So, thank you, and at this point, I'll
19 turn the podium over to Sarah Connelly.
20 DR. CONNELLY: Good morning, everyone. I
21 want to echo Dr. Cox's welcome today to all of our
22 speakers, panellists, and participants, and I have
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