The
FDA
approved
garetosmab
(Pasatru)
to
reduce
the
formation
of
new
heterotopic
ossification
lesions
and
disease
flares
in
adults
with
fibrodysplasia
ossificans
progressiva
(FOP),
the
agency
announced
on
Wednesday.
A
monoclonal
antibody,
garetosmab
works
by
binding
to
and
neutralizing
activin
A,
a
protein
that
plays
a
key
role
in
the
development
of
heterotopic
bone
growth
in
patients
with
the
ultra-rare
progressive
disease.
FOP
is
caused
by
a
mutation
in
activin
A
receptor-type
1
and
is
estimated
to
affect
fewer
than
500
people
in
the
U.S.
It
is
characterized
by
episodes
of
rapid
bone
growth
that
infiltrates
muscles,
tendons,
and
ligaments
and
seriously
impedes
patients’
mobility
and
daily
function,
including
their
ability
to
eat,
drink,
or
use
the
restroom
independently.
Most
patients
need
a
wheelchair
by
the
age
of
30,
and
the
disease
can
significantly
shorten
lives.
Bone
growth
around
the
rib
cage,
for
example,
can
result
in
breathing
problems
and
cardiorespiratory
failure.
Garetosmab’s
approval
was
supported
by
OPTIMA,
a
63-patient
phase
III
trial.
At
56
weeks,
the
placebo-controlled
study
showed
that
two
different
dosages
of
garetosmab
every
4
weeks
led
to
a
90-94%
reduction
in
the
number
of
new
heterotopic
ossification
lesions,
as
shown
on
low-dose
CT
scans.
Delivered
intravenously,
garetosmab
was
also
associated
with
fewer
investigator-assessed
disease
flares,
with
an
88%
reduction
versus
placebo
at
the
10
mg/kg
dose
and
a
15%
reduction
at
the
3
mg/kg
dose.
“For
people
living
with
FOP,
every
irregular
new
bone
formation
is
a
step
toward
disability
and
potential
loss
of
mobility,”
said
investigator
Kathryn
Dahir,
MD,
an
endocrinologist
at
Vanderbilt
University
in
Nashville,
Tennessee,
in
a
press
release
from
drugmaker
Regeneron.
“With
the
ability
to
reduce
the
number
of
new
bone
lesions
and
flare-ups,
we
now
have
a
new
treatment
that
can
positively
affect
patients.”
The
IV-administered
drug
is
just
the
second
to
be
approved
for
FOP,
following
the
2023
approval
of
the
oral
retinoid
palovarotene
(Sohonos),
which
carries
an
indication
for
kids
as
well.
A
planned
phase
III
trial
(OPTIMA-2)
will
soon
test
garetosmab
in
children
and
adolescents.
Common
adverse
events
in
OPTIMA
(occurring
in
at
least
10%
of
participants)
included
epistaxis,
abscess,
acne,
increased
hair
growth,
madarosis,
oral
ulcers,
folliculitis,
paronychia,
and
rash.
The
warnings
and
precautions
section
of
the
labeling
includes
risk
of
embryo-fetal
toxicity,
skin
and
soft
tissue
infections,
and
serious
nose
bleeds.
According
to
the
prescribing
information,
the
recommended
dose
of
garetosmab
is
10
mg/kg
every
4
weeks,
but
the
dosage
can
be
decreased
to
3
mg/kg
if
tolerability
is
an
issue.
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