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Abaloparatide, followed by alendronate, reduces risk for all fracture types in postmenopausal women
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Postmenopausal women treated with abaloparatide for 18 months followed by 2 years of alendronate therapy saw a significant reduction in both vertebral and nonvertebral fractures through 3.5 years compared with patients assigned placebo followed by alendronate, according to findings from the ACTIVExtend study.
At the 43-month timepoint, women treated with abaloparatide (Tymlos, Radius Health) saw an 84% relative risk reduction in the incidence of new vertebral fractures (P < .0001) and a 39% relative risk reduction in nonvertebral fractures (P = .038) compared with women who received placebo followed by alendronate. Additionally, women assigned abaloparatide experienced increases in bone mineral density at the lumbar spine, total hip and femoral neck that were sustained during alendronate therapy, as well as decreased levels of C-terminal telopeptide (CTX) and procollagen type 1 propeptides (P1NP).
“The findings really support how important it is to build up bone mass and restore and build up bone strength in that first 1 and a half years,” Felicia Cosman, MD, an endocrinologist at Helen Hayes Hospital Regional Bone Center in West Haverstraw, New York, and professor of medicine at Columbia University, told Endocrine Today. “Because afterward, we see this persistent reduction in fractures throughout the skeleton — an 84% reduction in vertebral fractures and a 39% reduction in nonvertebral fractures. We see those fracture reductions maybe with a drug like abaloparatide vs. placebo, but then, to see them continue — even after everyone is getting alendronate — that is what is so unusual about this kind of study. We haven’t seen anything like this before.”
In the ACTIVExtend study, researchers analyzed data from postmenopausal women who completed the initial ACTIVE phase 3 study who were assigned abaloparatide (n = 558) or placebo (n = 581) for 18 months, followed by 24 months of alendronate after a 1-month reconsent period. All fractures, regardless of trauma level, and major osteoporotic fractures were adjudicated as prespecified fracture endpoints for the cohort. Fracture risk reduction was measured from the beginning of ACTIVE to the end of ACTIVExtend.
At 43 months, five women in the abaloparatide/alendronate group (0.9%) sustained at least one new vertebral fracture vs. 32 in the placebo/alendronate group; 27 women in the abaloparatide/alendronate group sustained a nonvertebral fracture vs. 45 in the placebo/alendronate group. Researchers also observed a 50% risk reduction in major osteoporotic fractures in the abaloparatide/alendronate group vs. the placebo/alendronate group (P = .011).
Among women with no new vertebral fractures during the initial 18 months of the study, two in the abaloparatide/alendronate group and 13 in the placebo/alendronate group experienced new vertebral fractures during the extension phase. Adverse events were similar between groups, and there were no cases of atypical femur fracture or osteonecrosis of the jaw.
Cosman noted that all subgroups in the study, across a range of ages and baseline BMD values, responded equivalently well to the therapy.
“The idea is we will identify these patients with osteoporosis at high risk for fracture ... and then transition to a good antiresorptive drug to enhance the effects of the abaloparatide,” Cosman said. “This treatment sequence can really approach a cure. You really can minimize a person’s future risk for fracture in this way.”
In analyzing BMD and bone turnover markers with the sequential therapy, John P. Bilezikian, MD, professor of medicine and pharmacology at the College of Physicians and Surgeons at Columbia University and chief of the division of endocrinology and director of the metabolic bone diseases program at Columbia University Medical Center, and colleagues found that patients in the abaloparatide/alendronate group saw mean BMD increases of 14.4% at the lumbar spine, 6.4% at the total hip and 5.3% at the femoral neck, whereas mean BMD increases at the same areas for those in the placebo/alendronate group were 6.5%, 2.8% and 1.6%, respectively.
P1NP and CTX initially increased during the first months of the ACTIVE phase for those in the abaloparatide group; however, levels for both markers were below baseline levels for both groups by 43 months, according to researchers.
“Anabolic therapy with abaloparatide is highly effective for postmenopausal women at increased risk of osteoporotic fracture,” Henry G. Bone, MD, FACP, FACE, director of the Michigan Bone and Mineral Clinic, P.C., and head of endocrinology and metabolism at St. John Hospital and Medical Center in Detroit, and colleagues said in a press release announcing the ACTIVExtend findings. “However, it is essential to consolidate the gains in bone mass achieved with an anabolic with an antiresorptive agent. In the ACTIVExtend trial, the increased bone mass and reduced fracture risk achieved with abaloparatide were maintained and extended with alendronate, a low-cost antiresorptive agent.” – by Regina Schaffer
Reference:
Bone HG, et al, and Bilezikian JP, et al. Abstracts 1074, MO0655. Presented at: American Society for Bone and Mineral Research Annual Meeting; Sept. 8-11, 2017; Denver.
Disclosures: Bilezikian reports he is a consultant for Shire. Bone reports he is a consultant for Amgen. Cosman reports she has various financial ties with Amgen, Eli Lilly, Merck, Radius Health Inc., Sermonix and Tarsa.