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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 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.

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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.

A head-to-head BMD study evaluating patients continuing on alendronate or transitioning to Prolia®1

Objective1

This trial was conducted in postmenopausal women previously treated with alendronate to evaluate the effects of transitioning to Prolia® (denosumab) on safety, bone mineral density (BMD), and bone turnover markers (BTMs) in comparison with continued alendronate therapy.

Background2

  • In clinical practice, approximately half of patients stop taking their osteoporosis medication within the first year and may require a switch to a different therapy

Methods1

  • 1-year, multicenter, international, randomized, double-blind, double-dummy, parallel-group phase 3 trial
  • Adherence with oral study drug was evaluated at the end of the open-label run-in period and at months 1, 3, 6, 9, and 12 by counting tablets

Key Inclusion Criteria1

  • Postmenopausal women with a BMD T-score of ≤ -2.0 and ≥ -4.0 at the lumbar spine or total hip
  • Patients must have been receiving alendronate 70 mg/week for ≥ 6 months prior to screening

Patients Continuing on Alendronate Therapy or Transitioning to Prolia® Were Evaluated

ALN = alendronate; QW = once a week; SC = subcutaneous; Q6M = once every 6 months.

Primary Endpoint1

  • Percent change in total hip BMD from baseline to month 12

Select Secondary Endpoints1

  • Percent change in BMD at lumbar spine at 12 months
  • Safety endpoints included adverse events

Statistical Analysis:1

  • A step-down multiple testing procedure was used
    1. If noninferiority of denosumab for total hip BMD at month 12 was demonstrated by a lower bound of the 95% CI to be greater than -0.35%, then;
    2. superiority for the percent reduction in CTX-I at month 3 would be tested, and if the p value was < 0.5, superiority would be stated, and;
    3. superiority of total hip BMD at month 12 would be tested; if the p value was < 0.05, then superiority would be demonstrated, and;
    4. noninferiority at the lumbar spine would be tested and demonstrated if the lower bound of the 95% CI was greater than -0.22%

Patients who transitioned from alendronate to Prolia® showed statistically significant changes in total hip and lumbar spine BMD at month 121

  • Total Hip
  • Lumbar Spine

Prolia® demonstrated noninferiority and superiority
(vs alendronate) in total hip BMD

0.85% *†
Increase
in BMD

The lower limit of the confidence interval excluded the prespecified noninferiority margin (-0.35% for total hip), thus showing the noninferiority of Prolia® compared with alendronate. Superiority testing demonstrated the BMD increase with denosumab at the total hip was statistically superior to the change with alendronate (p < 0.0001).1

BMD data results are not meant to imply fracture efficacy and should not be extrapolated to predict differences in fracture efficacy. Head-to-head fracture studies have not been conducted.
  • *Primary efficacy endpoint.
  • (95% CI 0.44% - 1.25%), p < 0.01.

Prolia® demonstrated noninferiority and showed statistically significant changes in lumbar spine BMD1

1.18% *
Increase
in BMD

The lower limit of the confidence interval excluded the prespecified noninferiority margin (-0.22 for lumbar spine), thus showing the non-inferiority of Prolia® compared with alendronate1

BMD data results are not meant to imply fracture efficacy and should not be extrapolated to predict differences in fracture efficacy. Head-to-head fracture studies have not been conducted.
  • *(95% CI 0.63% - 1.73%), p < 0.01.

STAND adverse event profile

Overall, a similar number of participants in each treatment group reported adverse events during the study (78% Prolia®, 79% alendronate)1

SUMMARY OF ADVERSE EVENTS1

Alendronate (N = 249)
n (%)
Prolia® (denosumab) (N = 253)
n (%)
Any adverse event
196 (78.7)
197 (77.9)
Leading to study discontinuation
2 (0.8)
3 (1.2)
Death
0 (0.0)
1 (0.4)
Selected adverse events
Clinical fractures*
4 (1.6)
8 (3.2)
Gastrointestinal-related disorders
60 (24.1)
58 (22.9)
Infections
93 (37.3)
111 (43.9)
Neoplasms (benign or malignant)
9 (3.6)
9 (3.6)
Serious adverse events
16 (6.4)
15 (5.9)
Selected serious adverse events
Infections
3 (1.2)
1 (0.4)
Neoplasms (benign or malignant)
3 (1.2)
3 (1.2)

The most frequent adverse events in the denosumab and alendronate groups, respectively, were nasopharyngitis (13.4% and 10.8%), back pain (10.7% and 11.6%), bronchitis (6.3% and 5.6%), arthralgia (5.9% and 10.4%), constipation (5.1% and 4.8%), and pain in an extremity (4.7% and 8.4%).1

  • *On-study clinical fractures were as follows: Prolia®—2 foot, 2 wrist, 1 radius, 1 fibula, 1 humerus, 1 pelvis, 1 rib, 1 tibia; alendronate—1 foot, 1 wrist, 1 radius, 1 sacrum.