Real World Evidence Study Showed use of Prolia
Reduced Fracture Risk in Postmenopausal Women With Osteoporosis
Versus Alendronate Treatment
Longer Duration of Treatment With Prolia Was
Associated With Greater Improvements in Fracture Risk
Reduction
Data is From Real-World Study with Nearly Half
a Million Patients Comparing Prolia to Alendronate
THOUSAND
OAKS, Calif., May 8, 2023
/PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced new data from a
real-world study of nearly half of a million postmenopausal women
with osteoporosis in the U.S. medicare program showing
Prolia® (denosumab) injection reduced fracture risk in
patients versus oral alendronate, a frequently prescribed
bisphosphonate treatment. Treatment with Prolia was also associated
with greater reductions in fracture risk over time. The data were
presented during an oral presentation at the World Congress on
Osteoporosis, Osteoarthritis and Musculoskeletal Diseases
(WCO-IOF-ESCEO), in Barcelona, May 4-7,
2023.
To view the Multimedia News Release, please visit:
https://www.multivu.com/players/English/9094351-new-data-amgen-prolia-denosumab/
"Amgen has long been committed to reducing the impact of
osteoporosis, an underdiagnosed and undertreated disease that
increases the risk for bone loss and fracture for millions of
post-menopausal women," said Jyothis
George, vice president and global medical therapeutic area
head, General Medicine, at Amgen. "May is Osteoporosis Awareness
and Prevention Month, making this a great time to share these new
data about Prolia and the important role it can play in reducing
the risk of potentially life-altering fractures in these women at
high risk for fracture."
The retrospective, observational study assessed U.S. Medicare
beneficiary data on 478,651 postmenopausal women aged 66 or older
with no history of prior osteoporosis treatment who initiated
Prolia (n=89,115) or oral alendronate (n=389,536) treatment between
Jan. 1, 2012 and Dec. 31, 2018. The study's results showed that
Prolia reduced the relative risk of fracture across various
fracture types. At the end of follow-up, the overall relative risks
were:
- A 36% reduced risk of hip fractures (RR=0.64; 95% CI:
0.39-0.90)
- A 43% reduced risk of nonvertebral fractures, including
fractures to the hip, humerus, pelvis, radus/ulna and other femur
(RR=0.57; 95% CI: 0.42-0.71)
- A 30% reduced risk of hospitalized vertebral fractures,
(RR=0.70; 95% CI: 0.40-1.01) which was not statistically
significant
- A 39% reduced risk of major osteoporotic; nonvertebral and
hospitalized vertebral fractures (Relative Risk [RR]=0.61; 95% CI:
0.48-0.74)
- A 50% reduced risk of non-hip, nonvertebral fractures (RR=0.50;
95% CI: 0.35-0.64)
In addition, longer duration of treatment with Prolia was
associated with a greater reduction in major osteoporotic (MOP)
fracture risk. Prolia reduced risk of MOP fracture by: 9% at year 1
(RR=0.91; 95% CI: 0.85-0.97); 12% at year 2 (RR=0.88; 95% CI:
0.83-0.93); 18% at year 3 (RR=0.82; 95% CI: 0.77-0.87); and 31% at
year 5 (RR=0.69; 95% CI: 0.62-0.76); and 39% overall (RR=0.61; 95%
CI: 0.48-0.74). Patients were evaluated from treatment initiation
to first instance of a fracture outcome, treatment discontinuation
or switch, disenrollment from Medicare, or death.
"Although comparative trials between Prolia and bisphosphonates
showed superior bone mineral density increases with Prolia at key
skeletal sites, direct comparative studies with fracture as an
endpoint are lacking. These findings from nearly half a million
patients provide evidence that Prolia is associated with greater
fracture risk reduction than with alendronate," said Jeff Curtis, MD, MS, MPH, professor of medicine
in the Division of Clinical Immunology and Rheumatology at the
University of Alabama at Birmingham.
"This comparative effectiveness research employs rigorous
methodology that provides important insights that are relevant to
the care of women living with osteoporosis."
Prolia is the first approved therapy that specifically targets
RANK Ligand, an essential regulator of bone-removing cells
(osteoclasts). Prolia is approved and marketed in over 80 countries
worldwide. These findings provide important insights into the
effectiveness of Prolia versus oral alendronate on osteoporotic
fracture outcomes in post-menopausal women with osteoporosis at
high risk for fracture using real-world data.
About Osteoporosis-Related Fractures
Worldwide, one in three women, over the age of 50, will suffer a
fragility fracture due to osteoporosis and with an aging population
these numbers will rise.1 Yet despite this, there
is a large gap in the management and treatment of osteoporosis,
especially in the post-fracture setting, with an estimated four out
of five patients remaining undiagnosed and untreated after a
fracture.2 Without proper care or access to
effective intervention options, they remain at risk of painful and
disabling fractures in the future.
About Prolia® (denosumab)
Prolia is the first approved therapy that specifically
targets RANK Ligand, an essential regulator of bone-removing cells
(osteoclasts). Prolia is approved and marketed in over 80 countries
worldwide.
Prolia® U.S. Indications
Prolia® is indicated
for the treatment of postmenopausal women with
osteoporosis at high risk for fracture, defined
as a
history of osteoporotic fracture, or multiple risk factors
for fracture; or patients
who have failed or
are intolerant to other available osteoporosis
therapy. In postmenopausal women with osteoporosis,
Prolia® reduces the incidence of vertebral,
nonvertebral, and hip fractures.
Prolia® is indicated
for treatment to increase bone mass in men
with osteoporosis at high risk for
fracture, defined as a
history of osteoporotic fracture, or multiple risk factors
for fracture; or patients
who have failed or
are intolerant to other available osteoporosis
therapy.
Prolia® is indicated
for the treatment of glucocorticoid-induced
osteoporosis in men and women at high risk
of fracture who are either initiating or
continuing systemic glucocorticoids in a daily dosage
equivalent to 7.5 mg or greater of
prednisone and expected to remain on glucocorticoids for at least
6 months. High risk of fracture is defined
as a history of osteoporotic fracture, multiple
risk factors for fracture, or
patients who have failed or
are intolerant to other available osteoporosis
therapy.
Prolia® is indicated as a treatment to
increase bone mass in men at high risk for
fracture receiving androgen
deprivation therapy for nonmetastatic prostate cancer.
In these patients Prolia® also reduced the
incidence of vertebral fractures.
Prolia® is indicated as a treatment to
increase bone mass in women
at high risk for fracture receiving
adjuvant aromatase inhibitor therapy for
breast cancer.
Important Safety Information
Contraindications
Prolia® is contraindicated in patients with
hypocalcemia. Pre–existing hypocalcemia must be corrected
prior to
initiating Prolia®. Prolia® is contraindicated
in women who are pregnant and may cause fetal
harm. In women of reproductive potential,
pregnancy testing should be performed
prior to initiating
treatment with Prolia®. Prolia® is contraindicated in
patients with a history of
systemic hypersensitivity
to any component of the product. Reactions
have included anaphylaxis, facial
swelling and urticaria.
Same Active Ingredient
Prolia® contains the
same active ingredient (denosumab) found in
XGEVA®. Patients receiving Prolia®
should not receive XGEVA®.
Hypersensitivity
Clinically
significant hypersensitivity including anaphylaxis
has been reported with Prolia®. Symptoms
have included hypotension,
dyspnea, throat tightness, facial and
upper airway edema, pruritus, and urticaria.
If an anaphylactic or other clinically
significant allergic reaction occurs, initiate
appropriate
therapy and discontinue further use of Prolia®.
Hypocalcemia
Hypocalcemia may worsen with
the use of Prolia®, especially in patients
with severe renal impairment. In patients
predisposed to hypocalcemia and
disturbances of mineral metabolism, including
treatment with other calcium-lowering drugs,
clinical monitoring of
calcium and mineral levels is
highly recommended
within 14 days of Prolia® injection.
Concomitant use of calcimimetic drugs may worsen hypocalcemia risk
and serum calcium should be closely monitored. Adequately
supplement all
patients with calcium and vitamin D.
Osteonecrosis of the Jaw (ONJ)
ONJ, which can occur spontaneously,
is generally associated with tooth extraction and/or
local infection with delayed healing, and has been
reported in patients receiving Prolia®. An oral
exam should be performed
by the prescriber prior to initiation of
Prolia®. A dental examination with appropriate
preventive dentistry is recommended prior
to treatment in patients with risk factors for
ONJ such as invasive dental procedures,
diagnosis of
cancer, concomitant therapies (e.g., chemotherapy,
corticosteroids, angiogenesis
inhibitors), poor oral hygiene, and co-morbid disorders.
Good oral hygiene
practices should be maintained during treatment
with Prolia®. The risk of
ONJ may increase with
duration of exposure to Prolia®.
For patients requiring invasive dental
procedures, clinical
judgment should guide the management plan of
each patient. Patients who are suspected of
having or
who develop ONJ should receive care by a
dentist or
an oral surgeon. Extensive dental
surgery to treat ONJ may exacerbate the
condition.
Discontinuation of Prolia® should be considered
based on individual benefit-risk assessment.
Atypical Femoral Fractures
Atypical
low-energy, or low trauma fractures of
the shaft have been reported in patients receiving
Prolia®. Causality has not been established
as these fractures also occur in
osteoporotic patients who have not been
treated with antiresorptive agents.
During Prolia® treatment, patients
should be advised to report new or
unusual thigh, hip, or groin pain. Any patient
who presents with thigh or
groin pain should be evaluated to
rule out an incomplete femur fracture.
Interruption of Prolia® therapy should be considered,
pending a risk/benefit assessment, on an
individual basis.
Multiple Vertebral Fractures (MVF) Following Discontinuation of
Prolia® Treatment
Following discontinuation of Prolia® treatment,
fracture risk increases,
including the risk of multiple vertebral
fractures. New vertebral fractures occurred as
early as 7 months
(on average 19 months) after the
last dose of Prolia®. Prior vertebral
fracture was a predictor of multiple vertebral fractures after
Prolia® discontinuation. Evaluate an
individual's benefit/risk before initiating treatment
with Prolia®. If Prolia® treatment is discontinued,
patients should be transitioned to an
alternative antiresorptive therapy.
Serious Infections
In a clinical
trial (N= 7808) in women with
postmenopausal
osteoporosis, serious infections leading to
hospitalization were reported
more frequently in
the Prolia® group than in the
placebo group. Serious skin infections, as well as
infections of the abdomen,
urinary tract and ear were more frequent in
patients treated with Prolia®.
Endocarditis was also reported more frequently in Prolia®-treated
patients. The incidence of
opportunistic infections and the overall
incidence of infections were similar
between the treatment groups.
Advise patients to seek prompt medical attention if they develop signs
or symptoms of severe
infection, including cellulitis.
Patients on concomitant immunosuppressant agents or with
impaired immune systems may be at
increased risk for serious infections. In patients
who develop serious infections while on Prolia®,
prescribers should assess the need for
continued Prolia® therapy.
Dermatologic Adverse Reactions
In the same clinical
trial in women with postmenopausal
osteoporosis, epidermal and dermal adverse
events such as dermatitis, eczema
and rashes occurred at a significantly higher rate with Prolia®
compared to
placebo. Most of these events were not specific to the
injection site. Consider discontinuing Prolia® if
severe symptoms develop.
Musculoskeletal Pain
Severe and occasionally incapacitating bone, joint, and/or muscle pain has been reported
in patients taking Prolia®.
Consider discontinuing use if severe symptoms develop.
Suppression of
Bone Turnover
In clinical trials in women with
postmenopausal osteoporosis, Prolia® resulted
in significant suppression of
bone remodeling as evidenced
by markers of bone turnover and bone histomorphometry.
The significance of these findings
and the effect of long-term treatment are unknown.
Monitor patients for
these consequences, including ONJ, atypical
fractures, and delayed fracture healing.
Adverse Reactions
The most common adverse reactions
(>5% and more common than placebo) in
women with postmenopausal osteoporosis are back pain,
pain in extremity, musculoskeletal pain,
hypercholesterolemia, and cystitis. The most common adverse reactions (> 5% and more common than
placebo) in men with osteoporosis are back
pain, arthralgia, and nasopharyngitis. Pancreatitis
has been reported with Prolia®.
In women with postmenopausal
osteoporosis, the overall incidence of
new malignancies was 4.3% in the
placebo group and 4.8% in the Prolia®
group. In men with osteoporosis, new
malignancies were reported in no patients in
the placebo
group and 4 (3.3%) patients in
the Prolia® group. A causal
relationship to drug exposure has not been
established.
The most common adverse reactions
(> 3% and more common than active-control
group) in patients with
glucocorticoid-induced osteoporosis are back pain,
hypertension, bronchitis, and headache.
The most common
(per patient incidence ≥
10%) adverse reactions
reported with Prolia® in patients with
bone loss receiving ADT for
prostate cancer or adjuvant AI therapy for
breast cancer are arthralgia and back pain. Pain
in extremity and musculoskeletal pain have also been reported
in clinical trials. Additionally,
in Prolia®–treated men with
nonmetastatic prostate cancer receiving ADT,
a greater incidence of
cataracts was observed.
Denosumab is a human monoclonal antibody. As
with all therapeutic proteins, there is potential
for immunogenicity.
Please see full Prolia® Prescribing
Information, including Medication Guide.
About Amgen
Amgen is committed to unlocking the potential of biology for
patients suffering from serious illnesses by discovering,
developing, manufacturing and delivering innovative human
therapeutics. This approach begins by using tools like advanced
human genetics to unravel the complexities of disease and
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pioneer since 1980, Amgen has grown to be one
of the world's leading independent biotechnology
companies, has reached millions of patients around the world and is
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References
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Accessed November 18, 2019.
- Solomon DH, Johnston SS, Boytsov NN, McMorrow D, Lane JM, Krohn
KD. Osteoporosis medication use after hip fracture in U.S. patients
between 2002 and 2011. J Bone Miner Res. 2014 Sep;29(9):1929-37.
doi: 10.1002/jbmr.2202. PMID: 24535775; PMCID:
PMC4258070. https://pubmed.ncbi.nlm.nih.gov/24535775/.
Accessed May 2, 2023.
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