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Clinical studies of prolia®

Clinical studies on osteoporotic fracture risk with Prolia® (denosumab)

A number of clinical studies have been carried out to assess whether Prolia® (denosumab) decreases osteoporotic fracture risk. Studies assessing efficacy of denosumab treatment have been performed in both postmenopausal women and in male osteoporosis. In total, over 30 clinical studies have been conducted in different patient profiles, involving over 13,000 patients.

Clinical studies on Prolia® (denosumab) in postmenopausal osteoporosis

The main phase III randomized, double blinded study, titled ‘A Study to Evaluate Denosumab in the Treatment of Postmenopausal Osteoporosis: FREEDOM (Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months)’, looked at 7,808 women who had been through menopause and had a t score of less than -2.5 but not less than -4.0. The primary endpoint of the study was the incidence of new vertebral fractures after three years of denosumab treatment.

Results showed that Prolia® was associated with a significant reduction in vertebral fractures, non-vertebral fractures and hip fractures. Relative risk reduction at three years was 68% for vertebral fractures, 20% for non-spinal fractures, and 40% for hip fractures vs placebo. Furthermore, Prolia® (denosumab) increased bone mineral density (BMD) at all sites measured. These increased bone density was statistically significant in the denosumab group, vs placebo group.

A second smaller study, titled ‘A Randomised, Double-blind, Placebo-controlled Study to Evaluate denosumab in the Treatment of Bone Loss in Subjects Undergoing Aromatase Inhibitor Therapy for Nonmetastatic Breast Cancer’, was conducted in female patients with breast cancer using aromatase inhibitor therapy, which often results in bone loss. This study included women with a lumbar spine, total hip, or femoral neck bone density t score of less than -1.0 but not less than -2.5. The primary endpoint was to determine whether denosumab compared with placebo preserved lumbar spine bone density, which was met with statistical significance in the denosumab group. 

Clinical studies on Prolia® (denosumab) in male osteoporosis

Prolia® (denosumab) treatment for osteoporosis in men was assessed in a study involving 242 men with osteoporosis. This study, entitled ‘A multicenter, randomized, double-blind, placebo-controlled study to compare the efficacy and safety of denosumab 60 mg every six months versus placebo in Males with Osteoporosis’ looked at men with low bone mass at risk of fracture.

Prolia® (denosumab) treatment for osteoporosis in men was also assessed in a study involving 1,468 men with non metastatic prostate cancer. This study, entitled ‘A Randomised, Double-blind, Placebo-controlled Study to Evaluate denosumab in the Treatment of Bone Loss in Subjects Undergoing Androgen-deprivation Therapy for Nonmetastatic Prostate Cancer’, looked at men with histologically confirmed prostate cancer and a history of osteoporotic fracture. The study included men with a bone density t score at the lumbar spine, total hip, or femoral neck of less than -1.0 or a history of an osteoporotic fracture.

The primary endpoint of the study at 24 months was the change in BMD of the lumbar spine . Compared to placebo, denosumab significantly increased bone density at all clinical sites measured. All men received calcium (at least 1,000 mg) and vitamin D (at least 800 IU) supplementation daily. 

The study also looked at the number of patients who had spine fractures over three years. Prolia® demonstrated a significant relative risk reduction of new vertebral fractures at year 1, 2, and 3. In a prospectively planned exploratory analysis, significant increases in bone density were observed at the lumbar spine, total hip, femoral neck and the hip trochanter 1 month after the initial dose. 

Studies in postmenopausal women at high risk of fractures show that Prolia® is associated with a significant reduction in vertebral fractures, nonvertebral fractures and hip fractures.


Other clinical studies on PROLIA® (denosumab)

Several other supportive studies have been conducted in a variety of patient groups to assess the effects of denosumab therapy. One study in patients with varying degrees of renal impairment has not shown any notable changes in the pharmacokinetic profile of denosumab (please refer to section 4.4 of SmPC). 

In an interaction study, Prolia® did not affect the pharmacokinetics of midazolam, which is metabolized by cytochrome P450 3A4 (CYP3A4). This indicates that Prolia® should not alter the pharmacokinetics of drugs metabolized by CYP3A4.

Patients with severe renal impairment are at greater risk of developing hypocalcaemia. Adequate intake of calcium, vitamin D and regular monitoring of calcium is especially important in these patients.