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Subcutaneous abaloparatide viable option for postmenopausal women with osteoporosis

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February 3, 2017

Postmenopausal women with osteoporosis treated with subcutaneous abaloparatide for 18 months followed by alendronate for 6 months had improved bone mineral density and a reduced risk for fracture, according to findings from the ACTIVExtend study.

“Many osteoporosis experts have come to the conclusion that for patients who are at high risk for future fractures — either because of a history of prior fracture and/or very low bone density — treatment with bone building medication that stimulates bone growth to improve skeletal mass and structure is the best therapy,” Felicia Cosman, MD, medical director of the Clinical Research Center at Helen Hayes Hospital in Haverstraw, New York, told Endocrine Today. “Subsequent to the course of anabolic therapy, a potent antiresorptive agent should be utilized.”

Felicia Cosman
Felicia Cosman

Cosman and colleagues evaluated data from the ACTIVExtend study on 1,139 postmenopausal women with osteoporosis randomly assigned to 18 months of placebo followed by 6 months of alendronate (n = 581) or 18 months of subcutaneous abaloparatide (Radius Health) followed by 6 months of alendronate (n = 558) to determine the safety and efficacy of abaloparatide.

In ACTIVE and the first 6 months of ACTIVExtend, fewer participants in the abaloparatide group experienced a new morphometric vertebral fracture (0.55%) compared with the placebo group (4.4%) for an 87% RR reduction for new morphometric vertebral fractures (P < .001). The abaloparatide group had a 52% risk reduction for nonvertebral fractures (HR = 0.48; 95% CI, 0.26-0.89), a 58% risk reduction for major osteoporotic fractures (HR = 0.42; 95% CI, 0.21-0.85) and a 45% risk reduction for clinical fracture (HR = 0.55; 95% CI, 0.33-0.92) compared with the placebo group.

Gains in lumber spine BMD, total hip BMD and femoral neck BMD were higher among the abaloparatide group compared with the placebo group (P < .001 group differences for each site).

“The results of the ACTIVExtend study provide corroboration that this treatment sequence will provide a big benefit to bone mass and bone strength, assessed by resistance to fracture,” Cosman told Endocrine Today. “Women in the ACTIVE study who were assigned to abaloparatide for 18 months showed a rapidly reduced risk of vertebral and nonvertebral fractures. After all women switched to the antiresorptive agent alendronate, there was a further reduction in fracture occurrence in the group that transitioned from abaloparatide to alendronate, compared with the group that transitioned from placebo to alendronate. This suggests that the prior use of abaloparatide provided continued bone strengthening benefit even after making this switch. The study extension is ongoing, total extension period will be 2 years, and future analyses will be aimed at determining how long the benefit of abaloparatide persists and how many people with achieve a low risk status after the full 3.5 year therapy sequence.” – by Amber Cox

Disclosure: Cosman reports various financial ties with Amgen, Eli Lilly, Merck, Radius Health Inc., Sermonix and Tarsa. Please see the full study for a list of all other authors’ relevant financial disclosures.

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PERSPECTIVE
Robert D. Blank, MD, PhD
Robert Blank
Cosman and colleagues present results of a 6-month interim analysis of ACTIVExtend, in which subjects of both the abaloparatide and placebo arms of the phase 3 ACTIVE trial received open-label alendronate. In ACTIVE, paricipants received 18 months of abaloparatide or placebo. Completers were invited to participate in the extension study, and over 90% agreed to do so, yielding 581 placebo and 558 abaloparatide subjects for the extension study. During ACTIVE, those receiving abaloparatide experienced 86% fewer morphometric vertebral fractures and 43% fewer non-spine fractures than those receiving placebo. During the first 6 months of open-label alendronate, there were seven new morphometric vertebral fracture in the placebo group and none in the abaloparatide group. There were seven nonvertebral fractures in the placebo group and three in the abaloparatide group. These differences were not statistically significant. It will be interesting to see whether the final results, reflecting 24 months of open-label alendronate, demonstrate a difference in fracture incidence between the placebo and abaloparatide groups. This study is limited by its short duration to date and its relatively small size. It may therefore ultimately be underpowered to demonstrate a difference in fracture risk during the extension phase. The performance of an open-label extension study is laudable insofar as it reflects a realistic scenario in which abaloparatide might be used.

Robert Blank, MD, PhD
Endocrine Today Editorial Board Member, Chief of Endocrinology, Medical College of Wisconsin
Disclosure: Blank reports serving as a site investigator for Novo Nordisk’s DEVOTE study, receiving author royalties from UpToDate and holding stock in AbbVie.