SEATTLE — Denosumab treatment for up to 10 years appears to be associated with persistent reduction of bone turnover, continued increases in bone mineral density (BMD) without therapeutic plateau, and a low incidence of fractures in postmenopausal women with osteoporosis, according to new data from the FREEDOM Extension trial.
These findings are especially significant because they suggest that the benefit/risk profile for denosumab remains favorable in an aging population of postmenopausal women, researchers reported at the American Society for Bone and Mineral Research (ASBMR) 2015 Annual Meeting.
“The side effect profile is consistent with what has previously been reported. We haven’t found any new or different problems,” said lead study investigator Henry G. Bone III, MD, who is the director of the Michigan Bone and Mineral Clinic in Detroit.
In most cases, osteoporosis requires long-term therapy, and it is therefore important to maintain a favorable balance of benefit vs risk over that course of treatment, he explained.
Dr Bone presented the results from the 7-year, single-arm, open-label extension of the 3-year randomized, double-blind, placebo-controlled, multicenter, international phase 3 Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) study.
In this final analysis, the overall incidence of adverse events and serious adverse events with treatment with denosumab for up to 10 years remained consistent over the duration of the study. Additionally, the latest data indicate that treatment for up to 10 years produced progressively increased bone density measurements.
The original phase 3 FREEDOM fracture study enrolled 7,808 women with postmenopausal osteoporosis. They were randomly assigned to receive denosumab 60 mg or placebo subcutaneously every 6 months for 3 years, after which they could choose to enter a 7-year extension study.
Eligibility criteria for the extension study included completion of the pivotal phase 3 fracture trial, not missing more than one dose of the investigational product in the pivotal phase 3 fracture trial, and not receiving any other osteoporosis medications.
In the extension, all the patients, regardless of original randomization, received open-label denosumab 60 mg every 6 months. The long-term group received up to 10 years of treatment (3 years in the pivotal phase 3 fracture study and 7 years in the extension) and the cross-over group received up to 7 years of denosumab (3 years of placebo in the pivotal phase 3 fracture study, 7 years of denosumab in the extension).
Of the 4,550 patients who enrolled in the extension, 2,626 completed the study.
These new findings show that women treated with denosumab for 10 years achieved an average cumulative 10-year gain in BMD of 21.7% at the lumbar spine and 9.2% at the total hip, compared with baseline in the pivotal phase 3 fracture study. The annual rates of new vertebral and nonvertebral fractures remained low throughout the study period.
During the 7-year extension, 13 oral events were confirmed as osteonecrosis of the jaw, and 2 events were confirmed as atypical femoral fracture by independent adjudication committees. No atypical femoral fractures or osteonecrosis of the jaw cases were reported in the original 3-year core study.
Study investigator David Kendler, MD, who is the director of Prohealth Clinical Research in Vancouver, Canada, said it is vital that clinicians have long-term safety data to help guide their clinical judgment when choosing the right treatment regimen.
“The most important take-home message I think is that there is progressive long-term improvement through 10 years with a bone density that is going to continue to improve and with a fracture risk reduction throughout the 10 years. So, there doesn’t seem to be any loss of efficacy over time,” Dr Bone said in an interview with Endocrinology Advisor.
- Bone HG. Late-Breaking Abstract Presentations. Ten Years of Denosumab Treatment in Postmenopausal Women With Osteoporosis: Results From the FREEDOM Extension Trial. Presented at: American Society for Bone and Mineral Research (ASBMR) 2015 Annual Meeting; Oct. 9-12, 2015; Seattle.