1
DEPARTMENT OF HEALTH AND HUMAN
SERVICES
FOOD AND DRUG
ADMINISTRATION
CENTER FOR BIOLOGICS EVALUATION
AND RESEARCH
BIOLOGICAL RESPONSE MODIFIERS
ADVISORY COMMITTEE
MEETING #37
Thursday, March 18,
2004
8:30 a.m.
Hilton Hotel
Silver Spring,
Maryland
2
PARTICIPANTS
Mahendra S. Rao, M.D., Ph.D., Chair
Gail Dapolito, Executive Secretary
MEMBERS
Jonathan S. Allan, D.V.M.
Bruce R. Blazar, M.D.
David M. Harlan, M.D.
Katherine A. High, M.D.
Joanne Kurtzberg, M.D.
Alison F. Lawton
James J. Mul, Ph.D.
Thomas H. Murray, Ph.D.
Anastasios A. Tsiatis, Ph.D
CONSULTANTS
Jeffrey S. Borer, M.D.
Susanna Cunningham, Ph.D.
Jeremy N. Ruskin, M.D.
Michael E. Schneider, M.D.
Michael Simons, M.D.
INDUSTRY REPRESENTATIVE
John F. Neylan, M.D.
GUEST HEALTH CANADA REPRESENTATIVE
Norman Viner, M.D.
GUEST SPEAKERS
Stephen Epstein, M.D.
Silviu Itescu, M.D.
Robert J. Lederman, M.D.
Philippe Menasch, M.D.
Emerson C. Perin, M.D., F.A.C.C.
Doris A. Taylor, Ph.D.
NIH PARTICIPANTS
Richard O. Cannon, M.D.
Stephen M. Rose, Ph.D.
FDA PARTICIPANTS
Jesse L. Goodman, M.D., M.P.H.
Philip Noguchi, M.D.
Dwaine Rieves, M.D
Stephen Grant, M.D.
Richard McFarland, Ph.D., M.D.
Donald Nick Jensen, D.V.M., M.S.E.E.
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C O N T E N T S
PAGE
Call to Order
Mahendra Rao, M.D., Ph.D., Chair 5
Conflict of Interest Statement
Gail Dapolito, Executive
Secretary 5
Introduction of Committee 9
FDA Opening Remarks
Presentation of Certificate of
Appreciation
to Retiring Member
Jesse Goodman, M.D., M.P.H. 14
Philip Noguchi, M.D. 16
Open Committee
Discussion
Cellular Therapies for Cardiac Disease
FDA Introduction and Perspectives
Dwaine Rieves, M.D. 18
Guest Presentations
Overview Cardiomyopathy and Ischemic
Heart
Disease
Emerson Perin, M.D., Ph.D. 35
Q&A 65
Clinical Experience of Autologous
Myoblast
Transplantation
Philippe Menasch, M.D. 85
Q&A 115
Bone Marrow Cell Therapy for
Angiogenesis:
Present and Future
Steven Epstein, M.D. 128
Q&A 148
Cellular Therapies for Cardiac Disease
Richard McFarland, Ph.D., M.D. 159
Guest Presentations
Myoblasts: The First Generation Cells for
Cardiac Repair: What Have We Learned?
Doris Taylor, Ph.D. 169
Q&A 202
Preclinical Models - Hematopoietic and
Mesenchymal Cell Therapies for Cardiac
Diseases
Silviu Itescu, M.D. 219
Q&A 245
4
C O N T E N T S
(Continued)
From Mouse to Man: Is it a Logical Step for
Cardiac Repair?
Doris Taylor, Ph.D. 257
Q&A 275
Cardiac Catheters for Delivery of Cell
Suspension
Donald Nick Jensen, D.V.M.,
M.S.E.E. 292
Transcatheter Myocardial Cell
Delivery: Questions
and Considerations from the Trenches
Robert Lederman, M.D. 307
Q&A 333
Open Public Hearing 343
5
1 P R O C E E D I N G S
2 Call to Order
3 DR. RAO: Good
morning. Welcome to the
4
37th meeting of the Biological Response Modifiers
5
Advisory Committee.
6 Today's topic, as you all know, is related
7
to use of cells in cardiovascular disorders, and we
8
have a pretty full schedule for the next couple of
9
days, but before we can start the meeting, we have
10
to have a few sort of committee stuff that needs to
11
be gotten through, so I will turn the mike over to
12
Gail, so that she can make the mandatory
13
announcements.
14 Conflict of Interest Statement
15 MS. DAPOLITO:
Good morning.
16 The following announcement addresses
17
conflict of interest issues associated with this
18
meeting of the Biological Response Modifiers
19
Advisory Committee on March 18 and 19, 2004.
20 Pursuant to the authority granted under
21
the Committee Charter, the Associate Commissioner
22
for External Relations, FDA, appointed Drs. Jeffrey
23
Borer and Susanna Cunningham as temporary voting
24
members.
25 In addition, the Director of FDA's Center
6
1
for Biologics Evaluation and Research, appointed
2
Drs. Jeremy Ruskin, Michael Schneider, and Michael
3
Simons as temporary voting members.
4 Based on the agenda, it was determined
5
that there are no specific products considered for
6
approval at this meeting. The
committee
7
participants were screened for their financial
8
interests. To determine if any
conflicts of
9
interest existed, the agency reviewed the agenda
10
and all relevant financial interests reported by
11
the meeting participants.
12 The Food and Drug Administration prepared
13
general matters waivers for participants who
14
required a waiver under 18 U.S.C. 208.
Because
15
general topics impact on many entities, it is not
16
prudent to recite all potential conflicts of
17
interest as they apply to each member.
18 FDA acknowledges that there may be
19
potential conflicts of interest, but because of the
20
general nature of the discussions before the
21
committee, these potential conflicts are mitigated.
22 We note for the record that Dr. John
23
Neylan is participating in this meeting as a
24
non-voting industry representative acting on behalf
25
of regulated industry. Dr.
Neylan's appointment is
7
1
not subject to 18 U.S.C. 208. He
is employed by
2
Wyeth Research and thus has a financial interest in
3
his employer.
4 With regards to FDA's invited guest
5
speakers and guests, the agency determined that
6
their services are essential.
The following
7
disclosures will assist the public in objectively
8
evaluating presentations and/or comments made by
9
the participants.
10 Dr. Stephen Epstein is the Executive
11
Director, Cardiovascular Research Institute,
12
Washington Hospital Center. He
receives research
13
support, is a consultant to and has financial
14
interests with, firms that could be affected by the
15
committee discussions.
16 Dr. Philippe Menasch is employed at the
17
George Pompidou Hospital in Paris, France. He has
18
an association with a firm that could be affected
19
by the committee discussions.
20 Dr. Emerson Perin is employed by the Texas
21
Heart Institute. He receives
consultant fees from,
22
and is a scientific advisor to, firms that could be
23
affected by the committee discussions.
24 Dr. Doris Taylor is employed by the
25
University of Minnesota, Center for Cardiovascular
8
1
Repair. She receives consultant
fees from a firm
2
that could be affected by the committee
3
discussions.
4 Dr. Norman Viner is employed by the
5
Biologics and Radiopharmaceuticals Evaluation
6
Centre, Biologics and Genetic Therapies
7
Directorate, Health Canada, in Ottawa, Canada.
8 FDA participants are aware of the need to
9
exclude themselves from the discussions involving
10
specific products or firms for which they have not
11
been screened for conflicts of interest. Their
12
exclusion will be noted for the public record.
13 With respect to all other meeting
14
participants, we ask in the interest of fairness
15
that you state your name, affiliation, and address
16
any current or financial involvement with any firm
17
whose product you wish to comment upon.
18 Waivers are available by written request
19
under the Freedom of Information Act.
20 Thank you, Dr. Rao.
21 DR. RAO: Now
you know why I always have
22
Gail read that statement.
23 Before we start any committee work, I
24
would like to welcome two new members to the
25
committee, Dr. Murray and Dr. James Mul. We
9
1
generally introduce everyone on the committee
2
first, and we generally go in alphabetical order,
3
but this time I will try and start with the new
4
members, so that they can tell us a little bit
5
about themselves before we have the others
6
introduce themselves.
7 Introduction of Committee
8 DR. MULE: I am
Dr. Jim Mul. I am
9
currently the Associate Center Director for the H.
10
Lee Moffitt Cancer Center in Tampa.
I oversee all
11
translational research at the Center including all
12
cell-based therapies for the treatment of cancer as
13
it applies to the clinical treatment of patients
14
with advance tumors.
15 Prior to being in Tampa since September of
16
last year, I was at the University of Michigan
17
Cancer Center for 10 years, and prior to that, the
18
NCI for another 10 years, and I am delighted to be
19
here.
20 DR. MURRAY:
Good morning. I am Tom
21
Murray. I am President of the
Hastings Center,
22
which is celebrating its 35th years as the world's
23
first research institute devoted to ethics in
24
medicine and the life sciences.
25 I spent 15 years as professor at medical
10
1
schools including 12 at Case Western Reserve
2
University School of Medicine.
My interests are
3
fairly broad. I write a lot
about ethics and
4
ethics in the life science and science policy.
5 Thank you. I
am delighted also to be
6
here.
7 DR. RAO: If we
can go down the table, Dr.
8
Tsiatis.
9 DR. TSIATIS:
Hi. I am Butch Tsiatis. I
10 am
from the Department of Statistics at North
11
Carolina State University.
12 DR. BORER: My
name is Jeff Borer. I am a
13
cardiologist. I work at Weill
Medical College of
14
Cornell University in New York City.
I run a
15 division
and an institute at Cornell and, relevant
16
to this meeting, I am the Chairman of the
17
Cardiorenal Drugs Advisory Committee of the FDA.
18 DR. CUNNINGHAM:
Good morning. My name is
19
Susanna Cunningham. I am a professor
in the School
20
of Nursing at the University of Washington in
21
Seattle, and I am the consumer representative for
22
the Cardiovascular Renal Advisory Committee.
23 DR. SCHNEIDER:
I am Michael Schneider. I
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co-direct the Center for Cardiovascular Development
25
at Baylor College of Medicine, and our interests
11
1
are in the molecular genetics of cardiac muscle
2
formation, cardiac growth, cardiac cell apoptosis
3
and its relation to heart failure, and, relevant to
4
this meeting, cardiac progenitor cells of different
5
kinds.
6 DR. SIMONS:
Hi. I am Michael Simons. I
7
am Chief of Cardiology at Dartmouth Medical School.
8 I
work in the area of vascular biology, gene and
9
cell therapy.
10 DR. RUSKIN:
Good morning. I am Jeremy
11
Ruskin. I am a cardiologist and
12
electrophysiologist, and I direct the
Cardiac
13 Arrhythmia
Service at Massachusetts General
14
Hospital.
15 DR. NEYLAN:
Good morning. I am John
16
Neylan. I am a nephrologist and
an organ
17
transplanter by training. Currently, I am Vice
18
President of Clinical Research and Development at
19
Wyeth, and I serve as a industry representative to
20
the committee.
21 DR. KURTZBERG:
Hi. I am Joanne
22
Kurtzberg. I am a pediatric
oncologist. I direct
23
the Pediatric Bone Marrow and Stem Cell Transplant
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Program at Duke University and the Carolinas Cord
25
Blood Bank at Duke.
12
1 DR. ALLAN:
Hi. I am Jon Allan. I am a
2
virologist at the Southwest Foundation for
3
Biomedical Research. My area is
nonhuman primate
4
models for AIDS pathogenesis.
5 DR. CANNON:
Good morning. I am Richard
6
Cannon. I am at the National
Heart, Lung, and
7
Blood Institute. I am Clinical
Director of NHLBI,
8
and I am representing NHLBI at this meeting.
9 DR. ROSE: Good
morning. I am Stephen
10
Rose. I am Deputy Director for
the Recombinant DNA
11
Program in the Office of Biotechnology Activities
12
in the NIH.
13 DR. JENSEN:
Good morning. My name is
14
Nick Jensen. I am a reviewer in
the Center for
15
Devices and Radiological Health.
I am a
16
veterinarian and an engineer.
17 DR. McFARLAND:
Good morning. I am
18
Richard McFarland. I am a
reviewer in the
19
Pharm/Tox Branch in the Center for Biologics in the
20
Office of Cellular, Tissue and Gene Therapies.
21 DR. RIEVES:
Good morning. My name is
22
Dwaine Rieves. I am a medical
officer in FDA's
23
Center for Biologics Evaluation and Research.
24 DR. GOODMAN:
Good morning. I am Jesse
25
Goodman. I am the Center
Director of the Center
13
1
for Biologics. I would just like
to join in
2
welcoming especially the new members.
My
3
background is as an infectious disease physician in
4
academic medicine for many years.
5 DR. NOGUCHI: I
am Phil Noguchi, Acting
6
Director of the Office of Cellular, Tissue and Gene
7
Therapies in CBER.
8 DR. RAO: Thank
you, everyone.
9 We are very fortunate in having some