5 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, See More

PROLIA® IS THE ONLY FDA-APPROVED THERAPY FOR CANCER TREATMENT–INDUCED BONE LOSS (CTIBL) DUE TO HORMONE ABLATION THERAPY (CTIBL-HALT).1

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Prolia® Mechanism of Action

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Prolia® helps you treat patients at high risk for fracture with 5 indications

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When prostate cancer metastasizes to a patient’s bones, another treatment is available

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How many of your patients on hormone ablation therapy for nonmetastatic prostate cancer are at high risk for fracture?

When your patients are losing bone mass due to treatment for prostate cancer, help protect their bone health with Prolia®.1

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Prostate Cancer Treatment–induced Bone Loss Indication

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.1

Testosterone molecule for illustration purposes only.
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In the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®), denosumab (Prolia®) is included as a treatment option to increase bone density in certain men with nonmetastatic prostate cancer.2

National Comprehensive Cancer Network® (NCCN®) makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.

Among Men with Nonmetastatic Prostate Cancer

Androgen deprivation therapy can result in bone loss and is associated with fracture risk.3,4

How does androgen deprivation therapy (ADT) put men with nonmetastatic prostate cancer at high risk for fracture?

How does androgen deprivation therapy (ADT) put men with nonmetastatic prostate cancer at high risk for fracture?

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Bone Mineral Density (BMD): Comparison of ADT-induced BMD loss vs normal BMD loss in men and women3,4

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Reference data are obtained from population-based or review articles that measured bone loss at different sites (eg, lumbar spine or total hip).3,8

Patients with prostate cancer receiving ADT lost up to 4% BMD at the posteroanterior spine in the first year of therapy alone.4

Calcium and vitamin D supplementation alone may not be sufficient to prevent bone loss and fractures in patients receiving ADT.8

Fracture: Percent of patients with a fracture, 12 to 60 months after diagnosis of prostate cancer

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Data from a bone-related toxic effect subanalysis (n=26,685) of a study analyzing men listed in the linked database of the National Cancer Institute's Surveillance, Epidemiology, and End Results program and Medicare as having received a diagnosis of prostate cancer over a 12- to 60-month period. ADT included gonadotropin-releasing hormone (GnRH) agonist therapy or orchiectomy.9

Data have shown that nearly 1 in 5 men receiving multiple doses of ADT experienced a fracture within 4 years after the first year of diagnosis.9

Patients with prostate cancer receiving ADT experienced a 54% increase in relative incidence of fractures compared with patients not receiving ADT.9

Calcium and vitamin D supplementation alone may not be sufficient to prevent bone loss and fractures in patients receiving ADT.8

See how a phase 3 study evaluated the effects of Prolia® among men receiving ADT therapy for nonmetastatic prostate cancer1,5

See how a phase 3 study evaluated the effects of Prolia® among men receiving ADT therapy for nonmetastatic prostate cancer1,5

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Randomized, multinational, double-blind, phase 3 study assessing the effects of Prolia® vs placebo on BMD and new
vertebral fractures

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Men were stratified according to duration of androgen-deprivation therapy ( 6 months or > 6 months) and age ( 70 years or < 70 years). Men less than 70 years of age had either a BMD T-score at the lumbar spine, total hip, or femoral neck between –1.0 and –4.0, or a history of an osteoporotic fracture.

†Patients were instructed to take  1000 mg of calcium and  400 IU of vitamin D supplementation daily.5

SC = subcutaneous.

Primary endpoint:1,5

Percent change in: Lumbar spine BMD from baseline to 24 months

Secondary endpoints:1,5

Incidence of:

  • Newly diagnosed vertebral fracture through 36 months

Percent change in:

  • Lumbar spine BMD from baseline to 36 months
  • Total hip BMD from baseline to 36 months
  • Femoral neck BMD from baseline to 36 months

Prolia® increased BMD at key measured sites among men receiving ADT therapy for nonmetastatic prostate cancer1,5

Prolia® increased BMD at key measured sites among men receiving ADT therapy for nonmetastatic prostate cancer1,5

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24 Months: A significant increase in BMD at the lumbar spine compared with placebo (p < 0.0001; Primary Endpoint)1,5

Mean percent change in BMD at 24 months1,5

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36 Months: Prolia® demonstrated a continued increase in BMD through 36 months1,5

Mean percent change in BMD at 36 months1,2

Mean percent change in BMD at 36 months1,5

Mean percent change in BMD at 36 months1,5

Prolia® sustained reduction of new vertebral fractures up to 36 months6

Prolia® sustained reduction of new vertebral fractures up to 36 months6

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Prolia® significantly decreased the incidence of new vertebral fractures up to 36 months1,6

62% relative risk reduction in the incidence of new vertebral fractures at 36 months* (p = 0.0125, adjusted for multiplicity.1)

Relative risk reduction of new vertebral fracture at 12, 24, and 36 months1,5

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ARR = absolute risk reduction.

*Odds ratio relative to placebo adjusted for the stratification variables of age group and ADT duration at study entry.10

Prolia® safety and tolerability were evaluated in a pivotal trial among men with nonmetastatic prostate cancer receiving ADT over a 3-year period1

Prolia® safety and tolerability were evaluated in a pivotal trial among men with nonmetastatic prostate cancer receiving ADT over a 3-year period1

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Prolia® has been studied in a clinical trial of 1468 men with prostate cancer on ADT.5 The overall incidence of adverse events was similar between Prolia® and placebo (both approximately 87%).5

Adverse events (10% frequency in each treatment group)1

Placebo
(n = 725)
Prolia®
(n = 731)
Arthralgia 11.0% 12.6%
Back pain 10.2% 11.1%
Constipation 10.3% 10.0%
  • Pain in extremity and musculoskeletal pain have also been reported in clinical trials1
  • The percentage of patients who withdrew from the study due to adverse events was 7.0% and 6.1% for the Prolia® and placebo groups, respectively1
  • The overall rates of serious adverse events between Prolia® and placebo were 34.6% and 30.6%, respectively1

Important Safety Information

Prolia® is contraindicated in patients with hypocalcemia, in women who are pregnant and in patients with a history of systemic hypersensitivity to any component of the product. Patients receiving Prolia® should not receive XGEVA®. Clinically significant hypersensitivity, hypocalcemia, osteonecrosis of the jaw, atypical femoral fracture, multiple vertebral fractures following the discontinuation of Prolia® treatment, serious infections, dermatologic adverse reactions, musculoskeletal pain, and suppression of bone turnover have been reported in patients receiving Prolia®. Prolia® may cause fetal harm. It is not known whether Prolia® is excreted in human milk.

Please see additional Important Safety Information below, as well as Prescribing Information.

warning-icon If you have a clinical inquiry or would like to report an adverse event related to Prolia®, please visit www.amgen.com.

What dosing schedule should you follow for patients on Prolia®?

Prolia® is the only FDA-approved therapy for cancer treatment–induced bone loss (CTIBL) due to hormone ablation therapy (CTIBL-HALT).1

Be confident your Prolia® patients are receiving 6 months of therapy with each injection1

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Single-use prefilled 1 mL syringe1

The image above is for illustration purposes only and represents a snapshot in time. Actual dosing and duration of a particular patient's therapy should be based upon the product's approved labeling and the independent clinical decision of the provider.

Important Safety Information

Following discontinuation of Prolia® treatment, fracture risk increases, including the risk of multiple vertebral fractures. Evaluate an individual's benefit/risk before initiating treatment with Prolia®. If Prolia® treatment is discontinued, consider transitioning to an alternative antiresorptive therapy.

Prolia® is administered as 1 shot every 6 months1

  • 60 mg subcutaneous injection in the upper arm, upper thigh, or abdomen by a healthcare professional
    • – Pre-existing hypocalcemia must be corrected prior to initiating therapy with Prolia®
    • – Adequately supplement all patients with calcium and vitamin D
    • – Multiple vertebral fractures have been reported following Prolia® discontinuation
  • As a subcutaneous injection, Prolia® does not undergo first-pass metabolism11,12
  • May lessen patient pill burden

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, consider transitioning 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 Prolia® full Prescribing Information, including Medication Guide

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
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References: 1. Prolia® (denosumab) prescribing information, Amgen. 2. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Prostate Cancer Version 4.2019, 8/19/19. ©National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed August 19, 2019. To view the most recent and complete version of the guideline, go online to NCCN.org. 3. Gralow JR, Biermann JS, Farooki A, et al. NCCN task force report: bone health in cancer care. J Natl Compr Canc Netw. 2013;11(Suppl 3):S1–S50. 4. Greenspan SL, Coates P, Sereika SM, Nelson JB, Trump DL, Resnick NM. Bone loss after initiation of androgen deprivation therapy in patients with prostate cancer. J Clin Endocrinol Metab. 2005;90:6410-6417. 5. Smith MR, Egerdie B, Hernández Toriz N, et al, for the Denosumab HALT Prostate Cancer Study Group. Denosumab in men receiving androgen-deprivation therapy for prostate cancer. N Engl J Med. 2009;361:745-755. 6. Gnant M, Pfeiler G, Dubsky PC, et al; on behalf of the Austrian Breast and Colorectal Cancer Study Group. Adjuvant denosumab in breast cancer (ABCSG-18): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet. 2015;386(9992):433-443. 7. Ellis GK, Bone HG, Chlebowski R, et al. Randomized trial of denosumab in patients receiving adjuvant aromatase inhibitors for nonmetastatic breast cancer. J Clin Oncol. 2008;26:4875-4882. 8. Higano CS. Androgen-deprivation-therapy-induced fractures in men with nonmetastatic prostate cancer: what do we really know? Nat Clin Pract Urol. 2008;5:24-34. 9. Shahinian VB, Kuo Y-F, Freeman JL, Goodwin JS. Risk of fracture after androgen deprivation for prostate cancer. N Engl J Med. 2005;352:154-164. 10. Data on file, Amgen. 2008. 11. Turner PV, Brabb T, Pekow C, Vasbinder MA. Administration of substances to laboratory animals: routes of administration and factors to consider. J Am Assoc Lab Anim Sci. 2011;50:600-613. 12. Burkiewicz JS, Scarpace SL, Bruce SP. Denosumab in osteoporosis and oncology. Ann Pharmacother. 2009;43:1445-1455.