Page 167 - 80_01

Dry
eye
disease
compounds…

ISV-­-101

ISV-­-101
is
a
new
drug
of
the
company
InSite
Vision
incorporating
a
low

dose
of
the
non-­-steroidal
anti-­-inflammatory
(NSAID)
bromfenac
(Figure
12)
and
a

flow-­-able
mucoadhesive
polymer
of
DuraSite
technology
(75).
This
combination

enables
a
slow
release
of
bromfenac
over
a
longer
period
of
time.
Consequently
the

eye
aqueous
humor
is
absorbing
and
retains
a
higher
dose
of
bromfenac.
The

extension
of
the
duration
of
drug
residence
on
the
surface
of
the
eye
enables
better

penetration,
improving
efficacy,
safety
and
dosing.
Initial
data
from
previous

clinical
studies
evaluating
this
combination
demonstrated
a
favorable
safety

profile.
The
company
started
Phase
II
clinical
trials
(ClinicalTrials.gov
Identifier:

NCT01478555)
in
July
2012
on
150
patients
to
evaluate
the
safety,
tolerability,
and

efficacy
in
topical
administration
of
different
dose
regimens
of
the
ISV-­-101.

ESBA-­-105

ESBATechdeveloped
ESBA-­-105
a
single-­-chain
antibody
fragment
that

targets
tumor
necrosis
factor
alpha
(TNF-­-a)
(76).
Selective
inhibition
of
TNF-­-a
has

the
potential
of
modulating
the
inflammatory
and
immune
response.
Preclinical

studies
demonstrated
that
topically
administered
ESBA105
attains
therapeutic

levels
in
both
the
anterior
and
posterior
segments
of
the
eye
without
a
need
of
a

penetration
enhancer.
Consequently,
its
drug
penetration
and
ocular
bio-­-
distribution
appear
highly
attractive
for
clinical
use
to
treat
TNF-­-a
connected
eye

diseases
(77).
Alcon
after
the
fusion
with
ESBATech
conducted
Phase
II
clinical

trials
(ClinicalTrials.gov
Identifier:
NCT01338610)
in
April
2011
up
to
February

2012
to
evaluate
the
efficacy
of
ESBA-­-105
10
mg/mL
in
90
patients
with
severe

dry
eye
experiencing
persistent
ocular
discomfort.
The
results
demonstrated
that

the
compound
topically
applied
penetrated
into
the
anterior
chamber
of
the

human
eye
at
therapeutic
levels
(78).

DA-­-6034

Dong-­-A
Pharmaceutical
Co.,
Ltd
is
developing
a
MMP-­-9
inhibitor
called
DA-­-
6034,
consisting
of
7-­-carboxymethyloxy-­-3’,4’,5-­-trimethoxy
flavone
monohydrate

(Figure
13)
as
possible
treatment
for
dry
eye.
DA-­-6034
is
a
synthetic
derivative
of

eupatilin,
a
pharmacologically
active
flavone,
capable
to
increase
secretion
of

mucin-­-like
glycoprotein.
It
may
increase
as
well
the
secretion
of
some
mucin

species
in
conjunctiva
and
cornea.
Mucin
is
a
glycoprotein
lubricating
component

of
tear
film
able
to
weaken
moisture
loss
from
tear
evaporation.
Choi
and

163