2
BioTech Sage Report, January 2001
less advanced ulcers is to allow nor-
mal healing to occur by using dress-
ings and topical medications to pro-
tect the wound. Even when successful,
this therapy can require many months
of repeated treatments to achieve heal-
ing. The second approach utilizes
conventional skin grafts and is typi-
cally used for more advanced skin ul-
cers. However, the difficulty of heal-
ing donor sites and the risks associ-
ated with general anesthesia in the
elderly, who suffer the large majority
of chronic skin ulcers, often prevents
the use of skin grafts. Both treatment
approaches have a high failure rate.
Several biotech companies have
developed products that are believed
to be capable of facilitating wound
healing. At the top of
Biotech Sage
Report's (BSR) list are those biotechs
that generate skin grafts.
BSR consid-
ers this a perfect fit for biotechs. Skin
grafting is an important component of
the biotechnology arsenal, as it has
the potential to repair damaged tissue
with cells derived specifically from
the tissue itself. This should eliminate
the threat of rejection by the immune
system, and the possibility of intro-
ducing unwanted infectious agents
into the patient. This is not to say that
the procedure has drawbacks, as it
does. First, growing cells in cell cul-
ture in a laboratory has a strong po-
tential for changing the properties of
the cells. For example, hepatocytes
from the liver lose liver functions over
time in cell culture, and it is not
known whether lymphocytes cultured
in cell culture function normally in the
immune system when introduced back
into the patient. Another concern is
the time involved in creating a suffi-
cient number of cells for implantation.
Often, it can take weeks to generate
sufficient cells, and the time involved
may not be in the best interest of the
patient. Lastly, technology, as it cur-
rently stands, is not capable of devel-
oping complex tissues in cell culture
yet. However, advances are being
made, and someday study to evaluate
cell culture-derived tissues will be
undertaken. But for skin grafts, exist-
ing technology should be more than
suitable, as the skin is not as complex
as organs.
One biotech that has a product in
development is
Advanced Tissue
Sciences. Advanced Tissue Sciences
is developing Dermagraft, a dermal
replacement product, comprised of
dermal fibroblasts grown on a bioab-
sorbable scaffold. It is designed to
provide a healthy, metabolically ac-
tive dermal matrix in ulcers to support
wound closure. The positive aspect of
Dermagraft is that the cells grow and
divide, producing collagens, extracel-
lular matrix proteins and growth fac-
tors found in normal, healthy human
dermis. Advanced Tissue Sciences
has filed a New Drug Application
(NDA) to the Food and Drug Admini-
stration (FDA) for Dermagraft and are
awaiting the FDA's decision. Results
from the earlier Phase III clinical tri-
als were respectable, where 38.5% of
the evaluable patients who received
Dermagraft healed completely in
twelve weeks as compared to 31.7%
of the evaluable patients treated with
conventional therapy. In addition, at
thirty-two weeks, or six months after
the last application of Dermagraft,
57.5% of the evaluable Dermagraft
patients receiving product in the piv-
otal trial
manufac-
tured to
commercial
specification
achieved
complete
wound clo-
sure, as
compared to
only 42.4% of those receiving con-
ventional therapy alone. However,
there are factors that concern
BSR.
The FDA advisory committee, who
granted approval with the condition
that Advanced Tissue Sciences per-
form a post-marketing study to con-
firm efficacy and provide physician
training, originally reviewed Derma-
graft in January 1998. Since then, Ad-
vanced Tissue Sciences has conducted
additional studies. Unfortunately, sta-
tistical significance was not achieved
at the interim analysis, even though
"On the top
of our lists
are those
biotechs that
generate skin
grafts."
