ATLANTA -- Treatment of postmenopausal women with osteoporosis with subcutaneous abaloparatide for 18 months was associated with a significant decrease in vertebral, clinical, and osteoporotic fractures, according to research presented here during the .
In a trial known as ACTIVE conducted in women at low risk for osteoporotic fracture, subcutaneous abaloparatide was associated with a decrease in nonvertebral fractures of 86%, in all clinical fractures by 43%, and in major osteoporotic fractures by 70% compared with placebo, reported , director of the New Mexico Clinical Research and Osteoporosis Center in Albuquerque.
Action Points
- Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
- Note that this clinical trial of abaloparatide found that the novel agent was efficacious in terms of reducing the rate of fracture in post-menopausal women with osteoporosis.
- Be aware that nearly half of the cohort studied had a nonvertebral fracture history.
"Abaloparatide is a custom-designed molecule that has been created to have certain biologic properties. It's an osteoanabolic drug, so it stimulates bone formation and it has the ability to replace bone in places where the bone has been degraded from osteoporosis," Lewiecki told 麻豆传媒.
"At the same time, it's forming new bone it's also removing less bone than the current anabolic agent teriparatide [Forteo]. That combination of robust bone formation and minimal level of bone resorption allows it to provide an increase in bone density and strength and to restore the lost microarchitecture of bone from osteoporosis," he said.
ACTIVE was a phase III randomized trial that took place at 28 sites in 10 countries. It included 2,463 women ages 49 to 86 whose average T-score at the lumbar spine was -2.9.
One-quarter had a prevalent vertebral fracture and almost one half had a history of nonvertebral fracture.
Patients in the three-arm study received blinded daily subcutaneous 80-µg injections of abaloparatide or placebo, or open-label teriparatide at 20 µg, for 18 months. , the relative risk of new vertebral fractures versus placebo was 0.14 (95% CI 0.05-0.39, P<0.001).
To further elucidate the effects of abaloparatide, he and his colleagues also calculated the number needed to treat (NNT) in the study.
"Physicians and health economists often look at the number needed to treat as an index of effectiveness. The number needed to treat represents the average number of patients that would need to be treated to prevent one additional future fracture," Lewiecki explained in an interview.
In the ACTIVE population, the NNT for vertebral fractures with 18 months of abaloparatide therapy was 28, compared with 30 in patients who received teriparatide. For nonvertebral fractures, the NNT was 55 compared with 92 in the teriparatide group. For clinical fractures, the numbers were 37 vs 59, respectively, and for major osteoporotic fractures, the NNTs were 34 versus 75, respectively.
Ethical concerns about using placebo in high-risk patients led the ACTIVE investigators to recruit a lower risk population than has been the case in earlier studies. They therefore conducted an additional analysis to estimate the number needed to treat in a higher risk population.
"In general, all osteoporosis drugs are found to be more effective the higher the risk of the population being studied, and what's happened over time with clinical trials is that enrolled patients are at lower risk in current trials than in previous trials," Lewiecki said. "However, we can calculate the number needed to treat in the higher risk populations based on the fracture risk in the registration trials done in earlier drugs such as denosumab and alendronate."
Using data on fractures in the placebo group from the clinical trials for alendronate, , he and his colleagues calculated that if abaloparatide were used to treat the population in the FIT study, the number needed to treat would be about eight.
"So in a high-risk population, for every eight patients we treated we could prevent one new vertebral fracture. This is very reassuring for those of us thinking of using this drug if it's approved, that we can effectively prevent fractures without having to treat a whole lot of patients," he said.
An , posted online in the Journal of Bone and Mineral Research, determined that the benefits of fracture prevention were similar across various prespecified subgroups, including baseline BMD T-scores, prior fracture history, and age.
"In all subgroups, subcutaneous abaloparatide reduced vertebral fractures with an effect size that approximated the overall 86% reduction in relative risk," the researchers wrote.
Moreover, the overall 43% risk reduction for nonvertebral fractures was similar across all the subgroups, with hazard ratios below 1, they noted.
Disclosures
ACTIVE was sponsored by Radius Health.
Lewiecki reported financial relationships with Radius, Eli Lilly, Amgen, Merck, and Shire.
Primary Source
American Society for Bone and Mineral Research
Lewiecki E, et al "Abaloparatide-SC is an effective treatment option for postmenopausal osteoporosis: review of the number needed to treat compared with teriparatide" ASBMR 2016; Abstract MO0280.