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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 Read More

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 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. Close

For the treatment of postmenopausal women with osteoporosis at high risk for fracture

Prior to the open-label extension study, Prolia® was studied in a pivotal phase 3 fracture trial

Pivotal phase 3 fracture trial study design1,2

A multicenter, international, randomized, double-blind, placebo-controlled clinical trial that studied postmenopausal women between 60 and 91 years of age with a BMD T-score between -2.5 and -4.0 at the lumbar spine or total hip.

7808 patients were randomized to receive Prolia® 60 mg (n=3902) or placebo (n=3906) subcutaneously (SC) every 6 months (Q6M). All patients were supplemented with daily calcium and vitamin D.

Primary endpoint1,2

Incidence of new vertebral fractures at 3 years

Secondary endpoints1,2

Time to first nonvertebral fracture,* and time to first hip fracture

  • *Composite measurement excluding pathological fractures and those associated with severe trauma, fractures of the vertebrae, skull, face, mandible, metacarpals, fingers, and toes.

Results of the pivotal phase 3 fracture trial1,2

During the pivotal phase 3 fracture trial, in postmenopausal women with osteoporosis, Prolia® significantly reduced the relative risk of fracture at 3 years in vertebral (68%), hip (40%), and nonvertebral (20%§) sites (vs placebo).

There were no significant differences between subjects who received denosumab and those who received placebo in the total incidence of adverse events, serious adverse events, or discontinuation of study treatment because of adverse events.

Adverse reactions most commonly reported (≥5% and more common than placebo) in the Prolia®-treated group were back pain (34.7%), pain in extremity (11.7%), musculoskeletal pain (7.6%), hypercholesterolemia (7.2%), and cystitis (5.9%).

  • Absolute risk reduction: 4.8% (p < 0.0001).
  • Absolute risk reduction: 0.3% (p = 0.04).
  • §Absolute risk reduction: 1.5% (p = 0.01).

Please read the full Important Safety Information below before you continue to your review of the open-label extension study data.

With 10 years of safety data, you can help your patients weigh the risk and benefit of treatment with Prolia®3-5

Consider open-label extension study limitations when interpreting results. The open-label extension study is not blinded, not controlled, and includes inherent self-selection bias. A total of 351 patients (7.7%) had adverse events that led to discontinuation of Prolia® and 277 patients (6.1%) had adverse events that led to discontinuation of the study.

*At year 3, n-values represent patients who began the open-label extension study. At years 6 and 10, n-values represent patients who completed those respective years of the open-label extension study.3-5

Study Design

  • 7-year, international, multicenter, open-label, single-arm extension study
  • All patients receive Prolia® (denosumab) 60 mg SC Q6M, daily calcium and vitamin D

Key Inclusion Criteria

  • Must have completed the pivotal phase 3 fracture trial (received denosumab or placebo)
  • Missed no more than 1 dose of investigational product
  • Not receiving any other osteoporosis medications

Primary Endpoint

  • Safety and tolerability of up to 10 years of Prolia® administration

Secondary Endpoints

  • Percent change from baseline in bone mineral density (BMD) during 10 years of Prolia® administration
  • Incidence of vertebral and nonvertebral fractures during 10 years of Prolia® administration

Prolia® adverse event (AE) profile reflects data through 10 years3,4

Exposure-adjusted Subject Incidence of AEs (Rates per 100 Subject-years)3,4

PIVOTAL PHASE 3 FRACTURE TRIAL4
Years 1-3 Rate
OPEN-LABEL
EXTENSION STUDY3
Years 4-10 Rate
Placebo
(n = 3883)
Prolia®
(n = 3879)
Continued Prolia®
(n = 2343)
Cross-over Prolia®
(n = 2206)
All AEs
156.1
154.3
97.0
96.8
Infections
30.7
29.3
19.9
20.7
Malignancies
1.6
1.8
2.0
2.0
Eczema
0.6
1.1
0.9
0.9
Hypocalcemia
< 0.1
0.0
< 0.1
< 0.1
Serious AEs
10.4
10.6
10.3
10.1
Infections
1.3
1.5
1.5
1.4
– Cellulitis or Erysipelas
< 0.1
0.1
< 0.1
< 0.1
PIVOTAL PHASE 3 FRACTURE TRIAL4
Years 1-3 Rate
Placebo
(n = 3883)
Prolia®
(n = 3879)
All AEs
156.1
154.3
Infections
30.7
29.3
Malignancies
1.6
1.8
Eczema
0.6
1.1
Hypocalcemia
< 0.1
0.0
Serious AEs
10.4
10.6
Infections
1.3
1.5
– Cellulitis or Erysipelas
< 0.1
0.1
OPEN-LABEL EXTENSION STUDY3
Years 4-10 Rate
Continued Prolia®
(n = 2343)
Cross-over Prolia®
(n = 2206)
All AEs
97.0
96.8
Infections
19.9
20.7
Malignancies
2.0
2.0
Eczema
0.9
0.9
Hypocalcemia
< 0.1
< 0.1
Serious AEs
10.3
10.1
Infections
1.5
1.4
– Cellulitis or Erysipelas
< 0.1
< 0.1

Osteonecrosis of the Jaw From Open-label Extension Study6

  • 5.2 per 10,000 subject-years*

Atypical Femoral Fracture From Open-label Extension Study6

  • 0.8 per 10,000 subject-years*
  • *Exposure-adjusted subject incidence during the open-label extension study (years 4-10); rates include both the continued and cross-over groups.

Prolia® continued to increase lumbar spine and total hip BMD at 10 years in the open-label extension study5,6*

  • Lumbar Spine
  • Total Hip

BMD data results are not meant to imply fracture efficacy and should not be extrapolated to predict differences in fracture efficacy.
  • At 10 years, Prolia® patient bone biopsies (n = 22) showed normal bone architecture and quality8
  • LS Mean (95% CI)
  • *BMD measured as a secondary endpoint.
  • p < 0.05 compared with pivotal phase 3 fracture trial baseline.
  • Represents subjects from BMD substudy of pivotal phase 3 fracture trial.
  • §p < 0.05 compared with both pivotal phase 3 fracture trial and open-label extension study baselines.
  • The n-values represent number of subjects with observed BMD data. For baseline and year 3, these values represent observed BMD data during the pivotal phase 3 trial. In the open-label extension study, subjects were required to have 1 BMD measurement at baseline and at least 1 BMD measurement post baseline to be included in the analysis. As such, the number of subjects measured in the open-label extension study is greater than the number of subjects measured in the first 3 years.

Incidence of fracture with continued Prolia® through 10 years in the open-label extension study5,6

  • New Vertebral
  • Nonvertebral

Evaluation of New Vertebral Fractures in Open-label Extension Study (Years 4-10)5,6*

  • N = number of enrolled subjects in the study at the beginning of each period.
  • *Lateral radiographs (lumbar and thoracic) were not obtained at year 4, year 7, and year 9 (year 1, year 4, and year 6 of the open-label extension study). The data presented for years 4 and 5, years 7 and 8, and years 9 and 10 represent the respective annualized fracture incidence.3

Evaluation of Nonvertebral Fractures in Open-label Extension Study (Years 4-10)5,6*

  • N = number of enrolled subjects in the study at the beginning of each period.
  • *Percentages for nonvertebral fractures are Kaplan-Meier estimates.3