The FINANCIAL — Amgen on October 12 announced results from a seven-year, single-arm, open-label extension of the three-year randomized, double-blind, placebo-controlled, multicenter, international Phase 3 Fracture Reduction Evaluation of Denosumab in Osteoporosis every six Months (FREEDOM) study.
In this final analysis, treatment with Prolia (denosumab) for up to 10 years showed that the overall incidence of adverse events (AEs) and serious AEs remained consistent over the duration of the study with a low fracture incidence. In addition, postmenopausal women with osteoporosis on Prolia continued to show gains in bone mineral density (BMD) over 10 years. The findings were presented during a late-breaking oral presentation session at the American Society for Bone and Mineral Research (ASBMR) 2015 Annual Meeting in Seattle on October 12, according to Amgen.
“Osteoporosis generally requires long-term therapy, and it is important to maintain a favorable balance of benefit versus risk over that course of treatment,” said lead investigator Henry G. Bone III, M.D., director of the Michigan Bone and Mineral Clinic, Detroit. “Long-term therapy with denosumab for up to 10 years produced progressively increased bone density measurements. The safety profile remained consistent over the duration of the study, including a low fracture incidence. These long-term results are important for patients and those who care for them.”
The findings are from an extension of the pivotal Phase 3 FREEDOM fracture study (NCT00089791), which enrolled 7,808 women with postmenopausal osteoporosis. In the fracture study, participants were randomly assigned to receive Prolia (60 mg) or placebo subcutaneously every six months for three years, after which they could choose to enter a seven-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 investigational product (either Prolia or placebo) in the pivotal Phase 3 fracture trial, and not receiving any other osteoporosis medications. In the extension, all subjects, regardless of original randomization, received open-label Prolia (60 mg) every six months. The long-term group received up to 10 years of Prolia (three years in the pivotal Phase 3 fracture study and seven years in the extension) and the cross-over group received up to 7 years of Prolia (three years placebo in the pivotal Phase 3 fracture study, seven years Prolia in the extension). Of the 4,550 participants who enrolled in the extension, 2,626 completed the extension study.
David Kendler, M.D., FRCP(C), director, Prohealth Clinical Research in Vancouver, British Columbia and study investigator, noted, “Osteoporosis is a chronic condition, and many patients will be on lifelong therapy to help reduce the risk of fragility fractures. As a physician treating many patients with osteoporosis, long-term safety data is very important when considering the right treatment regimen.”
Subjects treated for 10 years with denosumab achieved an average cumulative 10-year gain in BMD of 21.7 percent at the lumbar spine and 9.2 percent at the total hip, compared to baseline in the pivotal Phase 3 fracture study. Overall rates of AEs and serious AEs were consistent with data reported previously in the extension study. Yearly rates of new vertebral and nonvertebral fractures remained low. During the seven years of the extension, 13 oral events were confirmed as osteonecrosis of the jaw (ONJ) and two events were confirmed as atypical femoral fracture by independent adjudication committees. No atypical femoral fractures or ONJ cases were reported in the original three-year core study.
“These 10-year findings from the final year of this open-label extension study provide important additional data to the significant body of evidence generated to inform long-term safety, including more than 100 original publications and presentations over the last seven years,” said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. “Together, the evidence from this pivotal Phase 3 fracture trial and its extension highlights the value of Prolia in the treatment of women with postmenopausal osteoporosis at high risk for fracture, as well as Amgen’s commitment to continued research in the field of osteoporosis.”