The Journal of Prevention of Alzheimer s Disease,
Год журнала:
2022,
Номер
unknown
Опубликована: Янв. 1, 2022
Aducanumab
(Aduhelm)
is
approved
in
the
United
States
for
treatment
of
patients
with
mild
cognitive
impairment
due
to
Alzheimer's
disease
or
AD
dementia.
Appropriate
Use
Recommendations
(AURs)
have
been
published
and
helped
guide
best
practices
use
aducanumab.
As
real-world
has
occurred
more
information
accrued,
AURs
require
refinement.
We
update
better
inform
appropriate
patient
selection
improve
shared
decision-making,
safety
monitoring,
risk
mitigation
treated
patients.
Based
on
evolving
experience
we
emphasize
importance
detecting
past
medical
conditions
that
may
predispose
amyloid
related
imaging
abnormalities
(ARIA)
increase
likelihood
ARIA
complications
including
autoimmune
inflammatory
conditions,
seizures,
disorders
associated
extensive
white
matter
pathology.
The
apolipoprotein
E
ε4
(APOE4)
genotype
strongly
exhibits
a
gene
dose
effect.
recommend
clinicians
perform
APOE
genotyping
care
decisions,
discussions
regarding
risk,
clinician
vigilance
concerning
ARIA.
most
occurs
during
titration
period
aducanumab,
suggest
performing
MRI
before
5th,
7th,
9th,
12th
infusions
detection.
Uncommonly,
be
recurrent
serious;
additional
parameters
discontinuation
taking
these
observations
into
account.
It
important
continue
learn
from
aducanumab
will
evolve
as
new
becomes
available.
This
AUR
does
not
address
efficacy,
price,
insurance
coverage
provided
assist
establish
New England Journal of Medicine,
Год журнала:
2022,
Номер
388(1), С. 9 - 21
Опубликована: Ноя. 30, 2022
The
accumulation
of
soluble
and
insoluble
aggregated
amyloid-beta
(Aβ)
may
initiate
or
potentiate
pathologic
processes
in
Alzheimer's
disease.
Lecanemab,
a
humanized
IgG1
monoclonal
antibody
that
binds
with
high
affinity
to
Aβ
protofibrils,
is
being
tested
persons
early
The Journal of Prevention of Alzheimer s Disease,
Год журнала:
2022,
Номер
unknown
Опубликована: Янв. 1, 2022
Alzheimer's
disease
is
a
progressive,
irreversible,
and
fatal
for
which
accumulation
of
amyloid
beta
thought
to
play
key
role
in
pathogenesis.
Aducanumab
human
monoclonal
antibody
directed
against
aggregated
soluble
insoluble
forms
beta.We
evaluated
the
efficacy
safety
aducanumab
early
disease.EMERGE
ENGAGE
were
two
randomized,
double-blind,
placebo-controlled,
global,
phase
3
studies
patients
with
disease.These
involved
348
sites
20
countries.Participants
included
1638
(EMERGE)
1647
(ENGAGE)
(aged
50-85
years,
confirmed
pathology)
who
met
clinical
criteria
mild
cognitive
impairment
due
or
dementia,
1812
(55.2%)
completed
study.Participants
randomly
assigned
1:1:1
receive
low
dose
(3
6
mg/kg
target
dose),
high
(10
placebo
via
IV
infusion
once
every
4
weeks
over
76
weeks.The
primary
outcome
measure
was
change
from
baseline
week
78
on
Clinical
Dementia
Rating
Sum
Boxes
(CDR-SB),
an
integrated
scale
that
assesses
both
function
cognition.
Other
measures
assessments;
secondary
tertiary
outcomes
assessed
cognition,
function,
behavior;
biomarker
endpoints.EMERGE
halted
based
futility
analysis
data
pooled
first
approximately
50%
enrolled
patients;
subsequent
analyses
larger
set
collected
up
declaration
followed
prespecified
statistical
analyses.
The
endpoint
EMERGE
(difference
-0.39
high-dose
vs
[95%
CI,
-0.69
-0.09;
P=.012;
22%
decrease])
but
not
0.03,
-0.26
0.33;
P=.833;
2%
increase]).
Results
substudies
engagement
dose-dependent
reduction
markers
pathophysiology.
most
common
adverse
event
amyloid-related
imaging
abnormalities-edema.Data
demonstrated
statistically
significant
across
all
four
endpoints.
did
meet
its
A
dose-
time-dependent
pathophysiological
observed
trials.
Alzheimer s & Dementia Translational Research & Clinical Interventions,
Год журнала:
2022,
Номер
8(1)
Опубликована: Янв. 1, 2022
Alzheimer's
disease
(AD)
represents
a
global
health
crisis.
Treatments
are
needed
to
prevent,
delay
the
onset,
slow
progression,
improve
cognition,
and
reduce
behavioral
disturbances
of
AD.
We
review
current
clinical
trials
drugs
in
development
for
treatment
Signal Transduction and Targeted Therapy,
Год журнала:
2023,
Номер
8(1)
Опубликована: Июнь 30, 2023
Abstract
Amyloid
β
protein
(Aβ)
is
the
main
component
of
neuritic
plaques
in
Alzheimer’s
disease
(AD),
and
its
accumulation
has
been
considered
as
molecular
driver
pathogenesis
progression.
Aβ
prime
target
for
development
AD
therapy.
However,
repeated
failures
Aβ-targeted
clinical
trials
have
cast
considerable
doubt
on
amyloid
cascade
hypothesis
whether
drug
followed
correct
course.
recent
successes
targeted
assuaged
those
doubts.
In
this
review,
we
discussed
evolution
over
last
30
years
summarized
application
diagnosis
modification.
particular,
extensively
pitfalls,
promises
important
unanswered
questions
regarding
current
anti-Aβ
therapy,
well
strategies
further
study
more
feasible
approaches
optimization
prevention
treatment.
Alzheimer s & Dementia,
Год журнала:
2022,
Номер
18(12), С. 2669 - 2686
Опубликована: Июль 31, 2022
Abstract
Blood‐based
markers
(BBMs)
have
recently
shown
promise
to
revolutionize
the
diagnostic
and
prognostic
work‐up
of
Alzheimer's
disease
(AD),
as
well
improve
design
interventional
trials.
Here
we
discuss
in
detail
further
research
needed
be
performed
before
widespread
use
BBMs.
We
already
now
recommend
BBMs
(pre‐)screeners
identify
individuals
likely
AD
pathological
changes
for
inclusion
trials
evaluating
disease‐modifying
therapies,
provided
status
is
confirmed
with
positron
emission
tomography
(PET)
or
cerebrospinal
fluid
(CSF)
testing.
also
encourage
studying
longitudinal
BBM
ongoing
future
However,
should
not
yet
used
primary
endpoints
pivotal
Further,
cautiously
start
using
specialized
memory
clinics
part
patients
cognitive
symptoms
results
whenever
possible
CSF
PET.
Additional
data
are
stand‐alone
markers,
considering
care.
In
this
13th
annual
installment
of
the
‘Antibodies
to
Watch’
article
series,
we
discuss
key
events
in
commercial
antibody
therapeutics
development
that
occurred
2021
and
forecast
might
occur
2022.
Regulatory
review
target
SARS-CoV-2
coronavirus
proceeded
at
an
unprecedented
pace
2021,
resulting
both
emergency
use
authorizations
full
approvals
for
sotrovimab,
regdanvimab,
REGEN-COV2,
as
well
others,
numerous
countries.
As
November
1,
a
total
11
had
been
granted
first
either
United
States
or
European
Union
(evinacumab,
dostarlimab
loncastuximab
tesirine,
amivantamab,
aducanumab,
tralokinumab,
anifrolumab,
bimekizumab,
tisotumab
vedotin,
REGEN-COV2).
The
global
seven
products,
however,
were
elsewhere,
including
Japan
(pabinafusp
alfa),
China
(disitamab
penpulimab,
zimberelimab),
Australia
(sotrovimab,
REGEN-COV2),
Republic
Korea
(regdanvimab).
Globally,
least
27
novel
are
undergoing
by
regulatory
agencies.
First
actions
Food
Drug
Administration
on
biologics
license
applications
faricimab,
sutimlimab,
tebentafusp,
relatlimab,
sintilimab,
ublituximab
tezepelumab
expected
quarter
Finally,
our
data
show
that,
with
antibodies
COVID-19
excluded,
late-stage
clinical
pipeline
grew
over
30%
past
year.
Of
those
development,
marketing
22
may
end
