Lead study author Felicia Cosman, MD stated, "Abaloparatide-SC increased bone mineral density in both the spine and hip and reduced the risk of vertebral and nonvertebral fractures consistently in postmenopausal women with osteoporosis regardless of their baseline characteristics, including age, bone mineral density, and whether or not they had prior fractures." Dr. Cosman is Medical Director of the Clinical Research Center at Helen Hayes Hospital and Professor of Medicine at Columbia University College of Physician and Surgeons in New York.
Study co-author Paul Miller, MD, FACP spoke at an Endocrine Society press conference about abaloparatide-SC and the phase 3 ACTIVE (Abaloparatide Comparator Trial In Vertebral Endpoints) trial. Dr. Miller is the Medical Director at the Colorado Center for Bone Research and distinguished Clinical Professor of Medicine at the University of Colorado Health Sciences Center in Lakewood, CO.
Dr. Miller explained, "Abaloparatide is a peptide that builds bone; that means it's anabolic to bone and stimulates bone formation, that's what anabolic means in that sense. Studies in animals and humans show bone mineral density increases, bone microarchitecture is restored, and bone strength is increased with abaloparatide. It has a unique mechanism of action at the PTH-1 receptor – there are several receptors on the osteoblasts, this particular receptor when it's stimulated by abaloparatide has a unique pathway of working to stimulate bone formation – and has limited movement of the calcium out of the bone and into the bloodstream, and it's optimized at a bone building profile."
Subjects and Methods
Overall, 2,463 postmenopausal women aged 49 to 86 years (mean=69 years) participated in the ACTIVE study. Subjects were equally distributed and placed into one of three arms:
The study was a prospective, double-blind, randomized, placebo-controlled trial with three arms: (1) placebo, (2) abaloparatide 80 mcg subcutaneous per day, and (3) teriparatide 20 mcg subcutaneous per day for 18 months.
During Dr. Miller's presentation, several proprietary slides were shown. In one slide reviewing bone mineral density (BMD) in the lumbar spine, he commented, "As you can see from the slide taking a look at the lumbar spine BMD, there's a significantly greater increase in bone mineral density at all time points, but particularly at month 6 and 12 of abaloparatide compared to teriparatide." Furthermore, if a straight line was drawn at each time point, the increase in BMD with abaloparatide occurred earlier than teriparatide.
Regarding fracture reduction, Dr. Miller stated, "The study primary endpoint was powered for a reduction in new vertebral fractures over 18 months, as compared to placebo; that was the primary endpoint. The primary endpoint was achieved; there was an 86% reduction in new vertebral fractures with abaloparatide that was significantly lower than with placebo."
Speaking to the slide of the Kaplan-Meier curves, "You can see that over the time of the study, the nonvertebral fracture reduction occurred early with abaloparatide, and continued to have a greater effect on lowering nonvertebral fractures as the study progressed. There were no differences in reductions in nonvertebral fractures between placebo and teriparatide in this particular study," said Dr. Miller.
There was a lower incidence rate of hypercalcemia with abaloparatide (3.4%) vs teriparatide (6.3%). While the incidence of dizziness was slightly higher with abaloparatide, it was not related to any arrhythmias. Dr. Miller indicated, "There was an overall acceptable safety profile between the two drugs and between placebo."
"The findings suggest that the investigational drug abaloparatide sub-Q, if approved, has the potential to provide consistent protection against fractures, and to increase bone mineral density in a broad group of postmenopausal women with osteoporosis, regardless of baseline age, BMD, or prior fracture history," stated Dr. Miller.
This study was funded by Radius Health, Inc.
Cosman F, Hattersley G, Miller PD, et al. OR01-2 Abaloparatide Significantly Reduces Vertebral and Nonvertebral Fractures and Increases BMD Regardless of Baseline Risk. The Endocrine Society's 98th Annual Meeting & Expo, Boston Convention and Exhibition Center, Boston, MA. April 1, 2016.