|
| |
| |
|
| |
|
Osteoporosis
Agents to Look for in the
future:
PREOS (parathyroid
hormone [rDNA
origin] for
injection)
|
|
The importance of
calcium for healthy
bones is well known.
Less widely
appreciated is the
critical role
parathyroid hormone
(PTH) plays in the
regulation of
calcium physiology
and bone replacement
processes. It has
now been well
established that the
normal daily rise
and fall of PTH
levels in the blood
have a profound
effect on bone, and
that injections of
PTH can stimulate
the growth of
structurally normal
new bone in cases
where bone has been
lost to
osteoporosis. In a
Phase 2 clinical
trial with over 200
postmenopausal
women, daily
injections of PREOS®
(parathyroid hormone
[rDNA origin] for
injection) produced
a clinically and
statistically
significant average
increase in bone
mineral density of
7.8% compared to the
baseline over a
one-year period.
TOP Study
The pivotal Phase 3
clinical trial with
PREOS®
(the Treatment of
Osteoporosis with
PTH or TOP Study)
was a double-blind,
placebo-controlled,
multi-national
trial. The primary
endpoint for this
study was vertebral
fracture reduction.
Secondary endpoints
included measuring
increases in bone
mineral density (BMD)
at several skeletal
sites. The TOP Study
concluded dosing in
September 2003.
Women
participating in the
study received
daily, subcutaneous
injections of PREOS®
or placebo for 18
months. Over an 18
month period, the
incidence of new
vertebral fracture
in the placebo group
was 3.37%. The
incidence of
fracture in the
PREOS®
treated group was
1.32%. This resulted
in a 61% decrease in
vertebral fracture
incidents when
compared to placebo.
In general, the
percentage of
subjects who
reported at least
one adverse event
were similar in the
placebo and PREOS®
groups.
PREOS®
(parathyroid hormone
[rDNA origin] for
injection) was
submitted to the FDA
for regulatory
review in the U.S.
May 2005. Preotact™
(parathyroid hormone
[rDNA origin] for
injection) was
submitted to the
EMEA for regulatory
review in Europe in
March 2005. In May
2006 the European
Commission issued
marketing
authorization for
Preotact.
|
calcilytics
|
|
In partnership with
GlaxoSmithKline,
NPS is developing
calcilytics, which
are orally active,
small molecules
targeted at bone and
mineral disorders,
such as
osteoporosis.
Calcilytics
antagonize calcium
receptors on
parathyroid glands
resulting in a
transient release of
the body’s own
stores of
parathyroid hormone
(PTH). In this way,
calcilytics may have
the potential to
produce the same
therapeutic effect
as PREOS®
(parathyroid hormone
[rDNA origin] for
injection), but
through oral
administration
rather than through
injection. They thus
represent an
attractive potential
follow-on product to
PREOS®.
Preclinical studies
showed that the
increased levels of
PTH achieved by
calcilytics were
equivalent to those
achieved by PTH
injection and
therefore may also
have the ability to
cause bone growth.
GlaxoSmithKline has
successfully
completed a
Phase 1 trial
with the lead
compound developed
from this
collaboration. The
purpose of this
trial was to
establish the safety
of calcilytics in
humans. This trial
also illustrated
proof-of-concept as
surrogate efficacy
biomarkers,
including PTH levels
and bone turnover
markers which may
indicate new bone
formation, were met.
NPS has retained
co-promotion rights
with GlaxoSmithKline
in North America for
marketing any drugs
that result from
this collaboration.
GlaxoSmithKline
plans to initiate a
later stage trial
later this year.
|
Protelos or
Strontium
Ranelate
|
|
This drug opens
a new direction
in
Osteoporosis
medication
because it not
only slows the
work of the
osteoclasts but
it stimulates
osteoblasts to
create new bone.
This is the
first drug that
does both.
Protelos (stronium
ranelate) has
been shown to be
highly effective
in reducing
fractures.
Servier
published
clinical tests
results showing
that in a five
year study of
5,091post
menopausal women
with
osteoporosis
showed:
- 16% risk
reduction in
non
vertebral
fracture
(p=0.04)
- 19% risk
reduction in
major
fragility
fractures
(hip, wrist,
pelvis &
sacrum, ribs
& sternum,
clavicle and
humerus)(p=0.031)
- 36% risk
reduction in
hip fracture
in a high
risk
elderly
population
(age > / =
74 years and
T score
- 8.2%
increase in
bone mineral
density at
the femoral
neck
(p<0.001)
- Protelos
was also
shown to
reduce
vertebral
fracture by
39%
(p<0.001).
Protelos
or strontium
ranelate, has
been approved
for use as an
Osteoporosis
medication in 27
European
Countries.
An announcement
by Servier, the
French
manufacturer of
this drug can be
found on their
new release page
of Servier's web
site.
If you wish to
review some of
the major
research studies
about Protelos,
go to
Osteoporosis
medication:
Strontium
Ranelate,
Protelos
|
|
Reclast /
Aclasta
|
|
Reclast, which
is marketed as
Aclasta in other
countries, is
the first
approved
treatment for
Paget's disease
patients to be
given as a
single-dose
infusion
compared to
current oral
therapies that
must to be taken
daily for up to
six months. This
medicine was
first launched
in Germany in
May 2005 for
Paget's disease
and is now
approved in more
than 50
countries.
Aclasta/Reclast
is administered
as a single 5
mg, 15-minute
intravenous
infusion by a
healthcare
professional.
"We believe
Aclasta/Reclast
provides a
critical new
treatment option
for people who
suffer from
Paget's
disease," said
James Shannon,
MD, Global Head
of Development
at Novartis
Pharma AG.
"Furthermore, we
are exploring
the full
clinical
potential of
this agent in
treating other
metabolic bone
diseases,
including
postmenopausal
osteoporosis."
The approval by
the US Food and
Drug
Administration
(FDA) for
Paget's disease
was based on
efficacy and
safety data
comparing a
single dose of
Aclasta/Reclast
with Actonel (30
mg risedronate)
taken daily for
60 days in two
identically
designed six
month trials.
Results combined
from both trials
showed 96
percent of
patients taking
Aclasta/Reclast
responded to
treatment
compared to 74
percent of
patients taking
Actonel at six
months. Results
of these
head-to-head
studies were
published in the
September 1,
2005 issue of
the New England
Journal of
Medicine[6].
These studies
also
demonstrated
that Aclasta/Reclast
starts working
faster, showing
a significant
difference as
early as two
months. Patients
who took Aclasta/Reclast
responded to
treatment after
an average of 64
days versus 89
days for those
taking Actonel.
Overall, the
number of
patients with
adverse events
was similar in
the Aclasta/Reclast
and Actonel
groups.
About Aclasta/Reclast
HORIZON, the
ongoing clinical
program of
Aclasta/Reclast,
is one of the
most
comprehensive
drug evaluation
programs ever
undertaken in
the area of
metabolic bone
diseases.
Approximately
13,000 patients
worldwide have
participated in
the program in
more than 400
centers. It is
the first
program to study
a once-yearly
dosing regimen
for the
prevention and
treatment of
postmenopausal
osteoporosis.
Other studies
involved in the
program include
prevention of
fractures
following a hip
fracture in men
and women, and
treatment of
corticosteroid-induced
osteoporosis and
male
osteoporosis.
The European
Medicines Agency
(EMEA) and FDA
are currently
reviewing
submissions for
the approval of
Aclasta/Reclast
as a once-yearly
treatment for
postmenopausal
osteoporosis.
Zoledronic acid,
the active
ingredient of
Aclasta/Reclast,
is also
available under
the brand name
Zometa for use
in other
indications.
|
|
Bazedoxifene
|
|
Bazedoxifene
is a
second-generation
selective estrogen
receptor modulator,
or SERM. Unlike its
older cousin Evista
(raloxifene),
bazedoxifene doesn't
appear to trigger
hot flashes in
post-menopausal
women.
Bazedoxifene is
currently under FDA
review for the
prevention of
postmenopausal
osteoporosis. If
approved,
bazedoxifene would
expand the options
currently available
to physicians for
the prevention of
osteoporosis.
|
|
Oporia (lasofoxifene)
|
Lasofoxifene (Oporia)
is a selective
estrogen receptor
modulator (SERM)
under development
for the prevention
and treatment of
osteoporosis and for
the treatment of
vaginal atrophy.
Clinical
trials
point
to
potent
effects
of
oporia
(Lasofoxifene)
on
bone
density
Preclinical
studies
show
Oporia
(lasofoxifene)
binds
to
estrogen
receptors
with
an
affinity
comparable
to
that
of
17beta-estradiol
and,
in
bone,
duplicates
many
of
the
effects
obtained
following
administration
of
estrogen.
These
properties
suggest
efficacy
in
osteoporosis
and
this
is
indeed
confirmed
in
phase
II
trials.
Compared
with
raloxifene,
the
current
leading
SERM,
Oporia
(lasofoxifene)
appeared
more
effective
in
improving
spinal
bone
density
in
post-menopausal
women.
Long-term
phase
II
data
show
that
the
improvements
in
bone
density
are
sustained
after
two
years
of
dosing.
Compared
with
raloxifene,
long-term
administration
of
Oporia
(lasofoxifene)
significantly
improved
bone
parameters,
such
as
bone
resorption
and
lumbar-spine
bone
mineral
density.
Reductions
in
LDL-C
were
also
more
pronounced
in
the
Oporia
(lasofoxifene)
treatment
arm
compared
with
raloxifene.
Some
10,500
women
have
been
enrolled
in
clinical
trials
in
which
the
effect
of
Oporia
(lasofoxifene)
on
bone
loss
prevention
and
fractures
is
being
assessed.
Outcome
data
from
these
large-scale
trials
is
awaited
with
interest.
|
|
|
|
|
Nelson, Miriam E. and Wernick, Sarah (2006). "
Strong Women, Strong Bones: everything you need
to know to prevent, treat and beat osteoporosis"
pp
240-241 |
|
|
|
|
Young People Get Osteoporosis Too Organization
Copyright © 2001 All rights reserved.
Revised: 07/19/07.
|
|
