SAN DIEGO – Bone density and fracture risk continued to improve from baseline in postmenopausal women taking denosumab for osteoporosis, according to data from a 2-year extension of the FREEDOM study in more than 4,000 women.
The original FREEDOM study (Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months) enrolled 7,808 postmenopausal women aged 60-80 years with osteoporosis to receive either a subcutaneous injection of denosumab (60 mg) or placebo along with daily calcium and vitamin D supplements every 6 months. All subjects had bone mineral density (BMD) T scores of less than –2.5 but not less than –4.0 at the lumbar spine or total hip. At 36 months, denosumab was associated with reductions of 68% in vertebral fracture and 40% in hip fracture (N. Engl. J. Med. 2009;361:756-65).
The FREEDOM results were the basis of the Food and Drug Administration’s approval of denosumab in June 2010. In the extension study, 2,343 patients from the original treatment group and 2,207 patients in the control group received the denosumab treatment for 2 years (as well as calcium and vitamin D), yielding follow-up data for up to 5 years of drug exposure, said Dr. Cesar Libanati at the annual meeting of the American Association of Clinical Endocrinologists.
Women in the long-term group who received denosumab for 5 years showed significant BMD improvements from baseline, of 13.7% in the lumbar spine and 7.0% in the total hip. Women in crossover group showed significant BMD improvements from the start of the extension study, of 7.9% in the lumbar spine and 4.1% in the total hip.
Patients in the crossover group showed significant increased in BMD from the extension study baseline similar to those seen in the long-term patients during their first 2 years of denosumab use, noted Dr. Libanati, clinical research medical director at Amgen Pharmaceuticals, maker of denosumab (Prolia), in Newbury Park, Calif.
During years 4 and 5, the annualized yearly incidence of new vertebral fractures in the long-term patients was steady at 1.4%, compared with 1.1% at the end of the 3-year FREEDOM study. The yearly incidence in the crossover treatment group was 0.9% for their first 2 years of denosumab exposure, compared with 2.5% in the first 2 years of the FREEDOM study.
The yearly incidence of nonvertebral fractures in the long-term patients was 1.4% after 4 years and 1.1% after 5 years. Nonvertebral fracture data for the crossover patients were not presented.
Denosumab remained well tolerated during the extension study. The adverse event profile was "similar in years 4 and 5 to that observed in the 3 years of the placebo-controlled FREEDOM study," Dr. Libanati said. Long-term patients also maintained the reductions in bone turnover seen during the original FREEDOM study, he added.
Dr. Libanati is employed by Amgen.