The
unique
dual
inflammation
blockade
of
investigational
lunsekimig
showed
promise
for
moderate-to-severe
asthma
in
the
phase
II
AIRCULES
study.
Targeting
both
thymic
stromal
lymphopoietin
(TSLP)
and
interleukin
(IL)-13,
lunsekimig
at
various
doses
achieved
statistically
significant
reductions
in
asthma
attacks,
with
a
55.3%
reduction
in
exacerbations
at
48
weeks
when
comparing
the
highest
dose
of
300
mg
every
28
days
against
placebo
(P=0.0016).
This
was
supported
by
secondary
endpoints
favoring
lunsekimig
at
this
dose,
reported
Njira
Lugogo,
MD,
of
the
University
of
Michigan
in
Ann
Arbor,
at
the
European
Respiratory
Society
(ERS)
Congress
in
Barcelona.
“This
trial
is
very
impactful,”
Lugogo
said.
“Lunsekimig
achieved
a
statistically
significant
and
clinically
meaningful
reduction
in
asthma
exacerbations.
You
saw
a
change
in
lung
function
that
was
rapid
and
sustained.
Patient-centric
outcomes
also
improved,
and
improvements
were
observed
across
subgroups,
with
a
greater
magnitude
of
response
in
those
with
greater
disease
severity,
including
frequent
exacerbations.
It
was
well
tolerated
at
all
doses.”
“Results
from
this
phase
II
study
support
dual
TSLP
and
IL-13
targeting
to
address
unmet
needs
in
individuals
with
moderate
to
severe
asthma,”
she
concluded.
Targeting
both
TSLP
and
IL-13
purportedly
gets
at
both
an
upstream
initiator
of
inflammation
and
a
downstream
driver
of
inflammation.
ERS
session
discussant
Lena
Uller,
PhD,
MSc,
of
Lund
University
in
Sweden,
cautioned
that
important
questions
remain
regarding
lunsekimig’s
mechanism
of
action.
“The
question
is
if
it
really
targets
both
these
upstream
and
downstream
mediators.
And,
of
course,
this
effect
that
you
see,
is
it
an
additive
effect
or
is
it
really
a
synergistic
effect?”
she
posed.
“I
think
for
future
research,
it’s
really
important
to
do
studies
where
you
can
compare
its
effectiveness
against
other
biological
treatments,
such
as
anti-TSLP,
to
really
compare
efficacy.”
One
such
TSLP
blocker
is
tezepelumab
(Tezspire),
a
human
monoclonal
antibody
that
has
been
FDA
approved
for
add-on
maintenance
treatment
of
severe
asthma
since
2021.
Also
relevant
is
the
IL-4
and
IL-13
blocker
dupilumab
(Dupixent),
approved
since
2018.
Still
more
options
for
asthma
biologics
on
the
market
include
omalizumab
(Xolair),
reslizumab
(Cinqair),
mepolizumab
(Nucala),
and
depemokimab
(Exdensur).
During
the
session’s
Q&A,
an
audience
member
asked
what
lunsekimig’s
dual
blockade
adds
to
the
current
biologic
landscape.
“The
majority
of
our
patients
are
partial
responders,
many
because
they
have
discordant
upper
and
lower
airway
responses
to
biologics,”
said
Lugogo.
“I
do
think
that
biologics
we
currently
have
tend
to
target
one
pathway,
but
there
is
redundancy
in
inflammation.”
“So,
the
question
is,
could
we,
as
we
go
into
the
next
generation
of
biologics
that
are
dual-,
maybe
tri-specific
targeted
biologics,
could
we
start
to
achieve
complete
remission?
That’s
always
been
our
dream,”
she
noted.
“I
think
this
is
the
next
frontier,
and
we’ll
learn
a
lot
more
as
we
start
to
engage
in
targeting
duplicative
and
redundant
pathways,
and
so
I’m
very
excited
about
this
new
trend
towards
targeting
multiple
inflammatory
pathways
in
asthma.”
Lunsekimig
remains
under
investigation
for
high-risk
asthma
in
the
phase
II
AIRLYMPUS
study
and
the
open-label
AIRPHRODITE
extension
study.
In
chronic
obstructive
pulmonary
disease,
the
biologic
has
proceeded
further,
with
phase
III
testing
in
the
PERSEPHONE
and
THESEUS
studies.
AIRCULES
was
a
double-blind
trial
conducted
on
several
continents.
The
investigators
sought
to
enroll
people
ages
18-80
in
Global
Initiative
for
Asthma
step
4-5,
on
medium-
to
high-dose
inhaled
corticosteroids,
with
at
least
one
asthma
exacerbation
in
the
past
year,
among
other
criteria.
The
study
included
685
patients
randomized
to
placebo
or
various
subcutaneous
doses
of
lunsekimig
(ranging
from
60
mg
once
every
8
weeks
to
300
mg
once
every
4
weeks).
Mean
age
was
about
52,
and
35%
were
men.
The
group
most
commonly
had
two
recent
prior
exacerbations
(49.3%)
or
one
(36.8%).
Baseline
fractional
exhaled
nitric
oxide
(FeNO)
was
37.0
ppb
on
average,
eosinophils
were
a
mean
0.377
×
109/L,
pre-bronchodilator
predicted
forced
expiratory
volume
in
one
second
was
60.8%,
the
average
5-Item
Asthma
Control
Questionnaire
score
was
2.8,
and
the
Standardized
Asthma
Quality
of
Life
Questionnaire
mean
score
was
4.1.
Lugogo
reported
a
higher
magnitude
of
response
in
patients
with
two
or
more
recent
exacerbations
or
high
type
2
inflammation
(FeNO
25+
ppb).
There
were
consistent
responses
to
lunsekimig
in
those
with
and
without
high
eosinophil
levels,
which
prompted
applause
in
the
room.
Safety-wise,
adverse
events
were
“pretty
much
what
you
would
expect
in
an
asthma
trial,”
said
Lugogo,
reporting
that
the
most
frequent
events
were
upper
respiratory
tract
infections
(12.2%)
and
nasopharyngitis
(9.6%)
in
the
lunsekimig
group.
There
were
no
treatment-emergent
adverse
events
leading
to
death,
and
importantly,
anti-drug
antibody
titers
were
generally
low
and
had
no
impact
on
pharmacokinetics,
efficacy,
or
safety.
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