Abaloparatide Followed by Alendronate Provides Rapid, Sustained Reduction in Fracture Risk for Postmenopausal Women With Osteoporosis

: Presented at WCO

By Chris Berrie

KRAKOW, Poland — April 23, 2018 — Abaloparatide followed by consolidation therapy with alendronate provides rapid and sustained fracture risk reduction throughout the skeleton for postmenopausal women with osteoporosis, according to results of a phase 3 extension trial, ACTIVExtend, reported at the World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (WCO).

At present, anabolic agents for reducing fracture risk in patients with osteoporosis are limited to 18 to 24 months of treatment. As bone loss can occur after discontinuation of these agents, the researchers sought to determine whether such treatment can be followed by an antiresorptive agent, to promote bone-mineral density (BMD) increases and continue the fracture protection for these patients.

René Rizzoli, MD, PhD, University Hospitals and Faculty of Medicine of Geneva, Geneva, Switzerland, presented these data from the ACTIVExtend study here on April 20. At the end of the 18-month ACTIVE study, “patients with either placebo or abaloparatide were switched to alendronate 70 mg weekly for 2 years,” Dr. Rizzoli noted.

The clinical characteristics of these patients were similar to those of the phase 3 ACTIVE study treatment groups. In ACTIVE, abaloparatide provided rapid increases in bone mineral density (BMD) at vertebral and hip sites, and significantly reduced vertebral and non-vertebral fractures compared with placebo in postmenopausal women with osteoporosis.

The proportions of patients with new vertebral fractures for placebo and abaloparatide in the original 18-month study (4.22% vs 0.58%; P< .001; 86% relative risk reduction) were similar for the 43 months for the placebo/alendronate group and the combination group (5.63% vs 0.92%; P< .001), indicating a sustained 84% relative risk reduction for the combination therapy.

Similarly, the relative risk reduction for non-vertebral fractures remained significantly in favour of combination therapy at 43 months (39%; P = .038). Although not powered for differences in hip fractures, Dr Rizzoli commented that, by 43 months, there was significant difference (5 vs. 0; P = .027).

In ACTIVExtend, the placebo/alendronate group (n = 568) and abaloparatide/alendronate group (combination; n = 544) were well matched for age (mean: 68.6 years), prevalently vertebral fractures (22%), and mean BMD at ACTIVE baseline (lumbar spine T-score: -2.9; total hip T-score: -1.9). Eighty-eight percent of enrolled patients completed the ACTIVExtend study.

For the safety analysis, the investigators observed similar levels of treatment-emergent adverse events for the placebo/alendronate group and the combination group (80.3% vs 81.7%), in terms of those defined as severe (6.9% vs 6.9%), serious (10.0% vs 11.8%), and leading to death (0.3% vs 0%) or discontinuation (6.2% vs 5.4%).

The most frequent treatment-emergent adverse events were again similar, as mainly arthralgia (10.0% vs 9.8%), upper respiratory tract infection (8.8% vs 7.2%), and back pain (5.9% vs 6.5%).

“Eighteen months of abaloparatide followed by consolidation therapy with 24 months of alendronate resulted in rapid and sustained fracture risk reduction throughout the skeleton,” Dr. Rizzoli concluded.

Abaloparatide is an anabolic parathyroid hormone (PTH)-related protein analogue that activates the PTH1 signalling pathway to stimulate bone formation.

The WCO Congress is sponsored by the International Osteoporosis Foundation (IOF) and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).

Funding for this study was supported by Radius Health Inc., Waltham, Massachusetts.

[Presentation title: Persistent Fracture Risk Reduction with Abaloparatide-SC Followed by 24 Months of Alendronate. Abstract OC2]


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