The
FDA
on
Wednesday
granted
accelerated
approval
to
pariglasgene
brecaparvovec
(Genglycos)
as
the
first
treatment
for
glycogen
storage
disease
type
Ia
(GSDIa),
an
inherited
metabolic
disorder
that
requires
frequent
consumption
of
cornstarch
to
prevent
severe
or
life-threatening
hypoglycemia.
People
with
GSDIa
cannot
properly
break
down
stored
glycogen
into
glucose
due
to
a
deficiency
of
glucose-6-phosphatase
(G6PC),
an
enzyme
that
helps
maintain
stable
blood
sugar
levels
between
meals.
As
a
result,
every
few
hours
patients
need
to
eat
raw
or
specially
formulated
cornstarch,
a
slow-digesting
carbohydrate.
The
one-time
adeno-associated
virus
vector
(AAV)-based
gene
therapy
delivers
a
functional
G6PC
gene
to
the
liver
to
target
the
root
cause
of
the
disease.
Approval
stipulates
use
in
adults
and
children
ages
8
years
and
up
in
combination
with
nutritional
management
as
a
means
of
reducing
cornstarch
intake.
An
estimated
1,500
to
2,500
Americans
have
GSDIa,
also
known
as
von
Gierke
disease.
“The
approval
of
Genglycos
represents
a
major
step
forward
for
the
GSDIa
community,”
David
Weinstein,
MD,
a
leading
expert
on
the
ultra-rare
disease,
said
in
a
press
release
from
drugmaker
Ultragenyx.
“Day-to-day
management
of
GSDIa
requires
a
relentless
regimen
of
raw
cornstarch
and
strict
dietary
management
that
can
be
extraordinarily
demanding
for
patients
and
families,”
said
Weinstein.
“Even
with
meticulous
adherence
to
this
regimen,
patients
must
be
perfect.
Any
missed
cornstarch
puts
patients
at
risk
of
severe
hypoglycemia,
seizures,
and
even
death.”
Phase
III
trial
data
supporting
the
approval
showed
that
pariglasgene
brecaparvovec
as
an
adjunct
to
nutritional
management
reduced
cornstarch
intake
by
41.1%
at
week
48,
as
compared
with
a
10.2%
reduction
in
the
placebo
group
(P<0.001).
On
average,
patients
in
the
gene
therapy
group
needed
one
fewer
dose
of
cornstarch
per
day
compared
with
the
placebo
group.
Under
the
accelerated
approval
pathway,
further
data
will
be
required
to
confirm
the
therapy’s
clinical
benefit.
Adverse
events
occurring
in
at
least
10%
of
pariglasgene
brecaparvovec-treated
patients,
and
at
a
higher
frequency
than
in
the
placebo
arm,
included
liver
enzyme
elevations
(71%),
nausea
(38%),
headache
(24%),
hypertriglyceridemia
(29%),
adrenal
insufficiency
(24%),
constipation
(19%),
hyperglycemia
(14%),
acne/dermatitis
acneiform
(19%),
Cushingoid
features
(14%),
and
anaphylaxis
(10%).
Warnings
and
precautions
in
the
drug’s
labeling
include
risks
for
hypersensitivity
and
infusion
reactions,
hepatotoxicity,
adrenal
insufficiency,
and
AAV
tumorigenicity.
The
FDA
said
the
drug
should
not
be
used
in
pregnancy,
and
contraindications
include
patients
with
severe
hepatic
fibrosis
or
cirrhosis.
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