Daily injection of the synthetic peptide abaloparatide for 18 months significantly reduced the risk of new vertebral and nonvertebral fractures in postmenopausal women with osteoporosis at high risk of fracture. This was reported according to the phase 3 ACTIVE (Abaloparatide Comparator Trial In Vertebral Endpoints) trial published in the August 16 issue of JAMA.
Dr. Miller and colleagues randomly assigned postmenopausal women (aged 49 to 86 years) with osteoporosis to receive daily injections for 18 months of placebo (n=821); abaloparatide 80 μg (n=824); or open-label teriparatide 20 μg (n=818). The women were considered to be at risk of osteoporotic fracture, with 63% of the women having a prior fracture.
The trial was conducted at 28 sites in 10 countries. Of the 2,463 women (average age, 69 years) originally enrolled in the trial, 1,901 completed the study.
Abaloparatide Linked to Reduced Risk for New Vertebral Fractures
New vertebral fractures occurred less frequently in the abaloparatide and teriparatide groups (0.58% and 0.84% groups, respectively) than in the placebo group (4.22%; P<0.001). The hazard ratio for new vertebral fracture with abaloparatide versus placebo was 0.14 (P<0.001). In addition, the estimated event rate for nonvertebral fracture was significantly lower with abaloparatide vs placebo: 2.7% vs 4.7%; P=0.049) in the placebo group. The estimated rate for nonvertebral fracture with teriparatide was 3.3%.
In addition, abaloparatide was linked to significantly greater increases in bone mineral density (BMD) at 18 months compared with placebo at total hip (4.18% vs -0.10%), femoral neck (3.6% vs -0.43%), and lumbar spine (11.2% vs 0.63%; P<0.001 for all comparisons). Increases in BMD also were significantly greater in the abaloparatide group versus the teriparatide group at the hip and femoral neck at 18 months (P<0.001). Differences between the two active groups were significant at the lumbar spine at 6 and 12 months, but this comparison “must be interpreted as exploratory,” the study authors noted.
The incidence of hypercalcemia was lower with abaloparatide vs teriparatide (3.4% vs 6.4%; P=0.006). Overall, no differences in the incidence of serious adverse events were found between the treatment groups (9.7% with abaloparatide, 10.0% with teriparatide, and 11.0% with placebo).
“Further research is needed to understand the clinical importance of risk difference, the risks and benefits of abaloparatide treatment, and the efficacy of abaloparatide vs other osteoporosis treatments,” the authors wrote.
Bar Is Set High for Fracture Prevention, Experts Say
“Ultimately, which therapy is selected for osteoporosis treatment may be less important than identifying and initiating an approved treatment,” wrote Anne R. Cappola, MD, ScM, and Dolores M. Shoback, MD, in an accompanying editorial.
“The bar is high for any preventive treatment—in the efforts to prevent a fracture that may or may not ever occur, prescribers do not want to prescribe a therapy that causes a new problem,” the experts commented. “The way forward for fracture prevention involves not only the development of better therapies to prevent fracture and easier delivery systems but also improved adoption of existing osteoporosis therapies for patients with prior fractures and minimization of adverse effects, particularly those associated with long-term use.”
Dr. Cappola is Professor of Medicine in the Division of Endocrinology, Diabetes, and Metabolism at Perelman School of Medicine at the University of Pennsylvania, Philadelphia, and Associate Editor, JAMA. Dr. Shoback is Professor of Medicine and Director of the Training Program in Diabetes, Endocrinology and Metabolism at the University of California, San Francisco.
The study was funded by Radius Health.
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September 1, 2016
Miller PD, Hattersley G, Riis BJ, et al. Effect of abaloparatide vs placebo on new vertebral fractures in postmenopausal women with osteoporosis: a randomized clinical trial. JAMA. 2016;316(7):722-733.
Radius Health. JAMA Publishes Positive Phase 3 Data for Abaloparatide in Postmenopausal Women With Osteoporosis. August 16, 2016. Available at: http://investors.radiuspharm.com/releasedetail.cfm?ReleaseID=984545
Cappola AR, Shoback DM. Osteoporosis therapy in postmenopausal women with high risk of fracture. JAMA. 2016;316(7):715-716.