Abaloparatide.

Abaloparatide is an investigational analog of human PTHrP (1-34) being developed for the treatment of osteoporosis. The amino-acid sequence of abaloparatide is identical to that of PTHrP in the first 20 amino-acids, while over half of the remaining amino-acids are different. Some studies in animals and in humans reported that abaloparatide presented a potent anabolic activity with reduced effects on bone resorption as compared to that observed with teriparatide. This may be due to a more transient signaling response of abaloparatide related to differing affinities of the two drugs to the specific conformations of the PTH1 receptor. In the ACTIVE study, a phase 3 fracture prevention trial, 2460 postmenopausal osteoporotic women at high risk for fracture were randomized to receive 18-months of either daily abaloparatide 80 μg s.c., placebo or teriparatide 20 μg s.c. The reduction in vertebral fracture rate with respect to placebo was 86% in the abaloparatide group and 80% in the teriparatide group. Abaloparatide also produced a significant 43% reduction in the rate of nonvertebral fractures (2.7 vs 4.0% with placebo, p=0.04) whereas teriparatide determined a 28% reduction (2.9 vs 4.0% with placebo, p=NS). Abaloparatide or teriparatide showed similar increases in BMD at lumbar spine, while the patients of the abaloparatide group showed significantly greater increases in BMD at both total hip (4.18 vs 3.26%) and femoral neck (3.60 vs 2.66%). Therefore, if the preliminary data of the ACTIVE study is confirmed, abaloparatide may become an important option for the anabolic treatment of postmenopausal osteoporosis.