Understanding and Treating Acromegaly

Comments

Transcription

Understanding and Treating Acromegaly
Understanding and
Treating Acromegaly
SOMAVERT is indicated for the treatment of acromegaly
in patients who have had an inadequate response to surgery
and/or radiation therapy and/or other medical therapies,
or for whom these therapies are not appropriate. The goal
of treatment is to normalize serum IGF-I levels.
Important Safety Information
SOMAVERT is contraindicated in patients with a history
of hypersensitivity to any of its components.
Patients on opioids often needed higher serum pegvisomant
concentrations to achieve appropriate IGF-I suppression
compared with patients not receiving opioids.
Patient View
Acromegaly
Incidence and prevalence1, 7
•T
he incidence of acromegaly is approximately 3-4 cases
per million persons per year
• < 20,000 cases in the United States
• The prevalence is about 60 cases per million
• Men and women are diagnosed equally with acromegaly
• Mean age at diagnosis = 40 years
Types of pituitary tumors1, 8, 9
•P
ituitary tumors account for about 15%
of intracranial neoplasms
•F
our main pituitary tumors are related to:
Lactotroph
(prolactinoma): 40-50%
Pituitary
gland
Corticotroph
(Cushing’s): 10-15%
Thyrotroph
(hyperthyroid): 1-5%
Somatroph
(acromegaly): 30%
Most pituitary tumors
are not malignant1
SOMAVERT is indicated for the treatment
of acromegaly in patients who have had an
inadequate response to surgery and/or radiation
therapy and/or other medical therapies, or for
whom these therapies are not appropriate.
The goal of treatment is to normalize serum
IGF-I levels.
The most common adverse events (>10% and
at frequencies greater than placebo) in 1 of the
3 active treatment arms in a placebo-controlled
study (N=112) included infection, pain, diarrhea,
nausea, flu syndrome, abnormal liver function
tests, and injection-site reaction.
Acromegaly
What is acromegaly?1
•A
cromegaly (ack-row-meg-uh-lee) is a rare
disease. It happens when there is too much
growth hormone and the body tissues and
organs grow too much
What is the pituitary gland?2
•T
he pituitary gland is a tiny organ in the
brain. It makes many hormones, including
growth hormone
• It helps your body maintain normal
functions, such as growth in childhood,
as well as healthy bones and muscles
What are pituitary tumors?1
•A
pituitary tumor happens when cells in the
pituitary gland grow out of control
•F
or many patients with acromegaly, the tumor
causes their pituitary gland to produce too
much growth hormone
Most pituitary tumors
are not malignant1
Acromegaly
Pull the
tab to
the right to
see a front
and side
view of the
pituitary
gland
Brain
Optic
chiasm
Pituitary
gland
Carotid
artery
Brain
Sphenoid
sinus
Sphenoid
sinus
Optic
chiasm
Pituitary
gland
Carotid
artery
Optic chiasm
Optic chiasm
Pituitary gland
Pituitary gland
Carotid artery
Carotid artery
Sphenoid sinus
Sphenoid sinus
Pull
Front View
Side View
Patient View
Relationship Between GH and IGF-I
In a fixed-dose pivotal trial
In a long-term dose titration trial
The initial rise in GH levels in patients treated with
SOMAVERT® (pegvisomant for injection) stabilized by 2 weeks6
GH levels remained stable with
SOMAVERT for 18 months
(the duration of the trial)10
Percent change in serum GH and IGF-I concentrations6
Serum concentrations of IGF-I and GH10
0
2
4
8
12
150
GH change from
baseline (%)
100
50
IGF-I (µg/L)
200
1000 6-month cohort
(n=131)
12-month cohort
(n=90)
18-month cohort
(n=38)
50
40
750
30
500
20
0
250
IGF-I change from -25
baseline (%)
-50
Placebo
SOMAVERT
10 mg/day
15 mg/day
20 mg/day
(n=26)
(n=26)
(n=28)
GH (µg/L)
Weeks
0
10
0
6
0
6
12
0
6
12
18
0
The first measurement of GH and IGF-I levels was made at 6 months after
initiation of therapy in all cohorts
A dose-dependent decrease in serum IGF-I was evident as early as
2 weeks after therapy initiation. As expected, this was accompanied
by an adversely proportional rise in serum GH, which was not
considered significant6
• The drop in IGF-I mirrors GH rise in this long-term study
In the same study, 82% of patients receiving 20 mg/day
had normal IGF-I at 12 weeks; 75% at 15 mg; 39% at
10 mg and 10% at placebo
Data from a long-term dose-titration trial in 160 patients treated with SOMAVERT for an
average of 425 days. Dosing began at 10 mg/day and was titrated up or down as necessary in
5 mg/day increments until the patient’s serum IGF-I levels were normal or until the maximum
dose (in this study) of 40 mg/day was reached (mean dose at 12 months was 18.0 mg/day;
mean dose at 18 months was 19.6 mg/day). Data presented are from a cohort of 38 patients
in a long-term, open-label, dose-titration extension trial in which patients with acromegaly
were treated for at least 18 consecutive months
Adapted from Trainer et al.4
Randomized, double-blind, multicenter, placebo-controlled, fixed-dose, 12-week study
in 112 patients with acromegaly previously treated with surgery, radiation therapy,
and/or medical therapy. Patients received a loading dose of 40 mg at the start of the trial.
•G
H levels approximately doubled (an increase from baseline
of 12-14 µg/L)
Adapted from van der Lely et al.10
The maximum indicated daily maintenance dose for SOMAVERT is 30 mg.
Important Safety Information
Functional effects of increased GH are prevented by GH receptor
blockade; therefore, patients on SOMAVERT should be carefully
observed for the clinical signs and symptoms of a GH-deficient state.
Tumors that secrete GH may expand and cause serious complications. All
patients with GH-secreting tumors, including those receiving SOMAVERT,
should be carefully monitored for changes in tumor volume.
Relationship
Between GH
and IGF-I
Relationship Between GH and IGF-I
Brain
Pituitary gland makes GH
What causes the signs and
symptoms of acromegaly?3
•W
hen there is too much growth hormone
(GH) in your body, it triggers the body
to make too much insulin-like growth
factor I (IGF-I)
GH triggers your body
to make IGF-I
•T
his causes organs and tissues
to grow too much
•O
ther signs and symptoms of
acromegaly may also appear
GH & IGF-I cause tissues
and organs to grow
Important Safety Information
Some people who have used SOMAVERT
have developed liver problems. These
problems generally disappeared when
those people stopped taking SOMAVERT.
Relationship
Between GH
and IGF-I
Patient View
Managing Signs and Symptoms
In the fixed-dose pivotal trial
SOMAVERT® (pegvisomant for injection) provided
improvements in signs and symptoms at each dose4
Mean change from baseline
(total score)
Improvement in total score for signs and symptoms for all dose levels
of SOMAVERT vs placebo at week 126
2
0
-2
-4
-6
+1.3
Placebo
(n=30)
10 mg/day
(n=26)
P=.022*
-2.5
SOMAVERT
15 mg/day
(n=24)
20 mg/day
(n=26)
P=.001*
P<.001*
Adapted from Trainer et al.4
Randomized, double-blind, multicenter, placebo-controlled, fixed-dose,
12-week study in 112 patients with acromegaly previously treated with
surgery, radiation therapy, and/or medical therapy. Mean baseline total
score for signs and symptoms was 15.2
In a post-hoc analysis of the same study,
-4.4
-4.7
Total score for signs and symptoms
*For a difference in mean change from baseline versus placebo (Dunett’s test).
•T
otal score for signs and symptoms was defined as the sum of all scores
from 0=absent to 8=worst for symptoms including fatigue, perspiration,
headache, arthralgia, and soft tissue swelling6
•A
t 12 weeks, mean % change from baseline increased (worsened) 16%
for placebo, and decreased (improved) 8% for 10 mg, 20% for 15 mg,
and 33% for 20 mg11
•A
t 12 weeks, ring size was smaller (improved) in groups treated with
15 or 20 mg of Somavert, compared with placebo6
91% of patients who achieved
normalized IGF-I levels also
experienced improvements in their
total signs and symptoms score
of acromegaly11
Study description: For the post-hoc analysis, a subset of 57 patients was
identified as having both IGF-I normalization and reported any signs
and symptoms of acromegaly at or after the visit at which IGF-I levels
were normalized4
Important Safety Information
Patients on opioids often needed higher
serum pegvisomant concentrations to achieve
appropriate IGF-I suppression compared with
patients not receiving opioids.
Managing Signs
and Symptoms
Managing Signs and Symptoms
Do you suffer from...1, 3
Pain in the joints (like knees or hips)
Headaches
Fatigue (weak muscles)
Sweating more than normal
Swelling in your hands or feet
Increased ring size
Talk to your health care professional about your signs
and symptoms of acromegaly
It is important to monitor your symptoms and discuss
them with your health care professional at each visit
Please see
the tear pad on
the back of the easel
Managing Signs
and Symptoms
Patient View
IGF-I
In a long-term dose-titration trial,
92% of patients (35/38) treated with SOMAVERT®
(pegvisomant for injection) achieved IGF-I reductions
within age-adjusted normal range after a mean of 55 weeks6
2500
Serum IGF-I (mg/mL)
2000
1500
94%
83%
100%
normal
range
within normal
range
within normal
range
25-39 (n=17)
40-54 (n=12)
≥55 (n=9)
1000
500
0
Adapted from van der Lely et al.10
Data from a long-term, dose-titration trial in 160 patients treated with
SOMAVERT for an average of 425 days. Dosing began at 10 mg/day
and was titrated up or down as necessary in 5 mg/day increments until
the patient’s serum IGF-I levels were normal or until the maximum dose
(in this study) of 40 mg/day was reached (mean dose at 12 months
was 18.0 mg/day; mean dose at 18 months was 19.6 mg/day). Data
presented are from a cohort of 38 patients in a long-term, open-label,
dose-titration extension trial in which patients with acromegaly were
treated for at least 18 consecutive months
Age (years)
Baseline
Nadir IGF-I level with SOMAVERT
Normal IGF-I range (age-adjusted)
In these patients, IGF-I levels remained normalized at
>90% of office visits for a mean duration of 1 year6
Important Safety Information
Tumors that secrete GH may expand and cause serious complications. All patients with GH-secreting tumors, including those
receiving SOMAVERT, should be carefully monitored for changes in tumor volume.
The maximum indicated daily maintenance dose for SOMAVERT is 30 mg.
Injection sites should be rotated daily to help prevent lipohypertrophy.
IGF-I
IGF-I
What is IGF-I?1, 3
Untreated symptoms
Treated symptoms
• IGF-I stands for insulin-like growth factor-I
• In acromegaly, your body makes too much IGF-I
and parts of your body grow too much
Sweating more
than normal
Why is it important to control my
IGF-I levels if I have acromegaly?11
•K
eeping IGF-I levels within the normal range
for people your age generally:
• Suggests that your disease is under control
•H
elps to improve the signs and symptoms
of acromegaly
Joint
pain
What treatments may help
me manage the symptoms
of acromegaly?5
•F
or most patients, the first treatment is surgery
to remove the tumor or reduce its size
Soft tissue
swelling
•M
any patients also need prescription medicines to help
control their hormone levels, including IGF-I levels
IGF-I
How SOMAVERT® (pegvisomant for injection) Works
Patient View
SOMAVERT is a growth hormone receptor antagonist (GHRa)6
SOMAVERT effectively binds to GH receptors on cell surfaces
• Blocks the binding of endogenous GH
• Reduces IGF-I production
•T
he initial increase in GH levels is attributed to loss of negative feedback
inhibition and does not diminish the efficacy of SOMAVERT
Growth Hormone Receptor antagonist
(SOMAVERT)
Growth Hormone
IGF-I
GH
GH
GHRa
GH receptor
GH receptor
Body
Body
Important Safety Information
Functional effects of increased
GH are prevented by GH receptor
blockade; therefore, patients on
SOMAVERT should be carefully
observed for the clinical signs and
symptoms of a GH-deficient state.
In subjects with systemic
hypersensitivity reactions, caution
and close monitoring should
be exercised when re-initiating
SOMAVERT therapy.
How
SOMAVERT
Works
How SOMAVERT® (pegvisomant for injection) Works
How does SOMAVERT work?6
Pituitary
Gland
SOMAVERT is a prescription medicine
for acromegaly. It is for patients whose
disease has not been controlled by
surgery, radiation, and/or other medical
therapies, or patients for whom these
options are not appropriate. The goal
of treatment with SOMAVERT is to have
a normal IGF-I level in the blood.
Important Safety Information
Your doctor may do blood
tests before and during
your treatment with
SOMAVERT. The
doctor is checking
that the IGF-I levels
in your blood are
normal and/or that
your liver is working
correctly. Your dose
of SOMAVERT may be
changed based on the results
of these tests.
If you have stopped SOMAVERT
because of an allergic reaction,
your doctor will carefully
monitor what happens if you
start SOMAVERT again.
GH
Body
Body
IGF-I
GH
GHRa
GH
receptor
GH
receptor
Growth Hormone (GH)
with acromegaly1,3
The pituitary gland receives
signals to produce GH. GH
signals the body to produce
IGF-I. This causes your organs
and tissues to grow too much
How
SOMAVERT
Works
Growth Hormone Receptor
antagonist (GHRa)1,6
SOMAVERT is a GHRa that
works by blocking GH action,
which lowers the levels of
IGF-I in the blood
Patient View
SOMAVERT® (pegvisomant for injection)
In a fixed-dose pivotal trial,
SOMAVERT demonstrated a dose-dependent
improvement in IGF-I normalization6
Percentage of patients achieving a normal serum IGF-I at week 126
100
Patients (%)
75%
82%
Dosing with SOMAVERT6
1. Establish IGF-I baseline
2. Initiate SOMAVERT therapy
50
• 40-mg loading dose under physician supervision
39%
• 10-mg daily self-administered at-home injections
10%
P=.02
P<.001
P<.001
10 mg/day
(n=26)
15 mg/day
(n=26)
20 mg/day
(n=28)
0
Placebo
(n=31)
SOMAVERT
The maximum indicated daily maintenance dose for SOMAVERT is 30 mg
•T
he majority of adverse events were mild to moderate and
of limited duration. They did not appear to be dose dependent6
Adapted from Trainer et al.4
Randomized, double-blind, multicenter, placebo-controlled, fixed-dose, 12-week study
in 112 patients with acromegaly previously treated with surgery, radiation therapy,
and/or medical therapy
SOMAVERT
3. Monitor IGF-I levels
•E
very 4-6 weeks until normalized;
every 6 months thereafter
4. T
itrate if IGF-I is not normalized
• In 5-mg increments or decrements
Important Safety Information
The most common adverse events (>10% and at
frequencies greater than placebo) in 1 of the 3 active
treatment arms in a placebo-controlled study (n=112)
included infection, pain, diarrhea, nausea, flu syndrome,
abnormal liver function tests, and injection-site reaction.
Acromegalic patients with diabetes mellitus being
treated with insulin and/or oral hypoglycemic agents
may require dose reductions of these therapeutic
agents after the initiation of therapy with SOMAVERT.
SOMAVERT® (pegvisomant for injection)
What can I expect from treatment
with SOMAVERT?6
The goal of treatment with SOMAVERT is to reach
a normal IGF-I level in the blood
In 2 clinical trials, the majority of patients treated with
SOMAVERT achieved normal IGF-I levels for their age
Vials not
actual size
•9
2% of patients treated with SOMAVERT achieved normal
IGF-I levels in a long–term study (at 55 weeks)
• This data comes from a part of a study involving 38 of the
original 160 patients who received SOMAVERT. Their dose of
SOMAVERT was changed until their IGF-I levels were normal
•8
2% of patients treated with 20 mg/day of SOMAVERT achieved
normal IGF-I levels in a short–term study*
• In the same short-term study, the overall signs and symptoms
of acromegaly improved in patients who took SOMAVERT
compared with those who didn’t take any medicine
—T
his study showed how patients rated the change in their
symptoms, which included joint pain, headaches, fatigue,
sweating, and soft tissue swelling
Actual size for self-administered, at-home injection
*This data is from a 12-week clinical trial that involved 112 patients with
acromegaly: 31 patients received no medicine; 80 were treated with SOMAVERT at
one of three doses. Results for patients achieving normal IGF-I levels for their age
were as follows: 10% of patients taking no medicine; 39% of those on 10 mg/day
of SOMAVERT; 75% of those on 15 mg/day; 82% of those on 20 mg/day.
Important Safety Information
Blood sugar levels may go down when taking SOMAVERT.
Be sure to tell your doctor if you use insulin or other medicines
(oral hypoglycemic medicines) for diabetes. The dose of these
medicines may need to be reduced when you use SOMAVERT.
If you need help affording your
treatments, Pfizer can help eligible
patients through the SOMAVERT
Copay/Coinsurance Support Program
and the Pfizer Bridge Program
The most common side effects with SOMAVERT are pain, infection,
reaction at the injection site, flu-like symptoms, nausea, and diarrhea.
These are not all of the possible side effects of SOMAVERT. For more
information, speak to your doctor.
SOMAVERT
SOMAVERT® (pegvisomant for injection) Safety Information
Indication
Important safety information regarding liver test monitoring
SOMAVERT is indicated for the treatment of acromegaly
in patients who have had an inadequate response to surgery
and/or radiation therapy and/or other medical therapies,
or for whom these therapies are not appropriate. The goal
of treatment is to normalize serum IGF-I levels.
onitor liver tests based on baseline values and changes
M
during therapy according to the schedule in the full
prescribing information. In clinical studies with SOMAVERT
ALT was >3X but <10X the upper limit of normal (ULN) in
patients treated with SOMAVERT (1.2%) vs placebo (2.1%).
ALT and AST elevations occurred within 4 to 12 weeks after
the start of therapy and did not appear to be related to the
dose 2 patients (0.8%) experienced elevations of ALT and
AST serum concentrations >10X the upper limit of normal
(ULN). In both patients, the elevations normalized after
discontinuation of the medicine. If a patient develops liver
test elevations, or any other signs or symptoms of liver
dysfunction while receiving SOMAVERT, please see Liver
Tests section of full Prescribing Information.
Important Safety Information
SOMAVERT is contraindicated in patients with a history
of hypersensitivity to any of its components.
Patients on opioids often needed higher serum pegvisomant
concentrations to achieve appropriate IGF-I suppression
compared with patients not receiving opioids.
Functional effects of increased GH are prevented by GH
receptor blockade; therefore, patients on SOMAVERT should
be carefully observed for the clinical signs and symptoms
of a GH-deficient state.
Acromegalic patients with diabetes mellitus being treated
with insulin and/or oral hypoglycemic agents may require
dose reductions of these therapeutic agents after the
initiation of therapy with SOMAVERT.
Important safety information regarding periodic tumor
size monitoring
Tumors that secrete GH may expand and cause serious
complications. All patients with GH-secreting tumors,
including those receiving SOMAVERT, should be carefully
monitored for changes in tumor volume. Overall, mean
tumor size was unchanged during the course of treatment
in clinical studies. Tumor volume change did not appear
to be influenced by whether or not patients had previously
received radiation therapy.
Important Safety
Information
for HCPs
In subjects with systemic hypersensitivity reaction, caution
and close monitoring should be exercised when re-initiating
SOMAVERT therapy.
The most common adverse events (>10% and at frequencies
greater than placebo) in 1 of the 3 active treatment arms in
a placebo-controlled study (N=112) included infection, pain,
diarrhea, nausea, flu syndrome, abnormal liver function tests,
and injection-site reaction.
Injection sites should be rotated daily to help prevent
lipohypertrophy.
The maximum indicated daily maintenance dose for
SOMAVERT is 30 mg.
Rx only
SOMAVERT® (pegvisomant for injection) Safety Information
Indication
SOMAVERT is a prescription medicine for acromegaly.
It is for patients whose disease has not been controlled
by surgery, radiation, and/or other medical therapies,
or patients for whom these options are not appropriate.
The goal of treatment with SOMAVERT is to have a normal
IGF-I level in the blood.
Important Safety Information for Patients
Do not use SOMAVERT if you are allergic to SOMAVERT
or anything that is in it.
Be sure to tell your doctor if you use narcotic painkillers
(opioid medicines) because the dose of SOMAVERT may
need to be changed.
Tumors that make growth hormone may grow in people
with acromegaly. Studies have shown that the size of these
tumors generally does not change for people who use
SOMAVERT. Even so, these tumors need to be watched
carefully by your doctor. Your doctor may ask you to have
a magnetic resonance imaging (MRI) test to monitor the size
of your tumor.
Blood sugar levels may go down when taking SOMAVERT.
Be sure to tell your doctor if you use insulin or other
medicines (oral hypoglycemic medicines) for diabetes.
The dose of these medicines may need to be reduced
when you use SOMAVERT.
Some people who have used SOMAVERT have developed
liver problems. These problems generally disappeared
when those people stopped taking SOMAVERT.
Stop the drug right away and call your doctor if you get
any of these symptoms:
• Your skin or the white part of your eyes turns yellow
(jaundice)
• Your urine turns dark
• Your bowel movements (stools) turn light in color
• You do not feel like eating for several days
• You feel sick to your stomach (nausea)
• You have unexplained tiredness
• You have pain in the stomach area (abdomen)
Your doctor may do blood tests before and during your
treatment with SOMAVERT to check that the IGF-I levels
in your blood are normal and/or that your liver is working
correctly. Your dose of SOMAVERT may be changed based
on the results of these tests.
If you have stopped SOMAVERT because of an allergic
reaction, your doctor will carefully monitor what happens
if you start SOMAVERT again.
The most common side effects with SOMAVERT are pain,
infection, reaction at the injection site, flu-like symptoms,
nausea, and diarrhea. These are not all of the possible
side effects of SOMAVERT. For more information, speak
to your doctor.
A different site should be used each day for injections.
This can help prevent skin problems such as lumpiness
or soreness.
SOMAVERT has not been studied in pregnant women.
It is not known if SOMAVERT passes into the mother’s
milk or if it can harm the baby.
If you have questions about the Pfizer Bridge
Program, please call toll free at 1-800-645-1280,
or visit www.somavert.com.
You are encouraged to report negative side
effects of prescription drugs to the FDA. Visit
www.fda.gov/medwatch or call 1-800-FDA-1088
Important Safety
Information
for Patients
References
1. Melmed S. Acromegaly. N Engl J Med 2006;355:2558-2573.
2. T
he pituitary gland. Hormone Foundation Web site.
www.hormone.org/pituitary_gland.cfm.
Updated March 2008. Accessed May 25, 2010.
3. Melmed
S, Jackson I, Kleinberg D, Klibanski A.
Current treatment guidelines for acromegaly.
J Clin Endocrinol Metab. 1998;83(8):2646-2652.
4. T
rainer PJ, Drake WM, Katznelson L, Freda PU,
Herman-Bonert V, van der Lely AJ, et al. Treatment of
acromegaly with the growth hormone-receptor antagonist
pegvisomant. N Engl J Med. 2000;342(16)1171-1177.
5. M
elmed S, Colao A, Barkan A, Molitch M, Grossman AB,
Kleinberg D. Guidelines for acromegaly management: an
update. J Clin Endocrinol Metab. 2009; 94(5):1509-1517.
6. Somavert [package insert]. New York. NY: Pfizer; 2010.
7. E
zzat S, Forster MJ, Berchtold P, Redelmeier DA, Boerlin V,
Harris AG. Acromegaly: clinical and biochemical features
in 500 patients. Medicine. 1994;73(5):233-240.
8. Jameson JL, Kasper DL, Fauci AS, Braunwald E, Longo
DL, Hauser SL. Harrison’s Endocrinology. Columbus, OH.:
McGraw Hill. 2006.
9. D
egroot LJ, Jameson JL. Endocrinology. 4th ed.
Philadelphia, PA: Saunders.
10. van der Lely AJ, Hutson RK, Trainer PJ, Besser GM,
Barkan AL, Katznelson L, et al. Long-term treatment
of acromegaly with pegvisomant, a growth hormone
receptor antagonist. Lancet. 2001;358:1754–1759.
11. Post-hoc analysis of the data appearing in N Engl J Med.
2000; 342(16)1171-1177.
References