Abaloparatide Reduced Fracture Incidence in Postmenopausal Women

SEATTLE — Treatment with abaloparatide, as compared with placebo or teriparatide, significantly decreased major osteoporotic fractures in postmenopausal women, according to the latest data from the phase 3 ACTIVE trial.

At the American Society for Bone and Mineral Research (ASBMR) 2015 Annual Meeting, researchers reported that women with postmenopausal osteoporosis who received 18 months of daily abaloparatide subcutaneous injection experienced a considerable reduction in the incidence of major osteoporotic fractures compared with placebo.

Responder analysis also showed greater increases in bone mineral density (BMD) at three combined anatomical sites (total hip, femoral neck, and lumbar spine) compared with placebo or teriparatide at 6, 12, and 18 months.

“Calculating the risk of major osteoporotic fractures is a way to identify patients who are risk for fracture using the FRAX algorithm.  Since major osteoporotic fractures are predictive of future fractures, reducing major osteoporotic fractures is an important goal in the treatment of postmenopausal women with osteoporosis,” said lead study investigator Lorraine Fitzpatrick, MD, Chief Medical Officer at Radius Health in Radnor, Pennsylvania.

“In this clinical trial, abaloparatide reduced the incidence of major osteoporotic fractures by 70% compared to placebo and has the potential to reduce the risk of future fractures,” added Dr Fitzpatrick, who presented the data at the meeting.

The Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE) is a randomized, double-blind, placebo-controlled trial evaluating fracture prevention in 2463 women with postmenopausal osteoporosis.

In the trial, patients were randomly assigned to 18 months of daily abaloparatide 80 mcg, matching subcutaneous placebo, or open-label subcutaneous teriparatide 20 mcg. All patients also received calcium and vitamin D supplements.

Previously reported data from this trial showed abaloparatide significantly reduced the incidence of new vertebral, nonvertebral, and clinical fractures while significantly increasing BMD at the lumbar spine, total hip, and femoral neck. In addition, abaloparatide had a favorable safety profile.

These new data showed that patients treated with abaloparatide also had significantly lower incidences of hypercalcemia than those receiving teriparatide. The most common adverse reactions that led to study discontinuation of abaloparatide included dizziness, heart palpitations, and headaches.

“Abaloparatide has anabolic effects, and it is a potential new option that may be useful in the treatment of postmenopausal women with osteoporosis. In this clinical trial, abaloparatide provided early fracture risk reduction for new vertebral fractures, nonvertebral fractures and major osteoporotic fractures in postmenopausal osteoporosis,” Dr Fitzpatrick told Endocrinology Advisor. “It has a nice safety profile and the dizziness was not associated with any falls.”

Dr Fitzpatrick explained that fractures are not only common but also lead to an enormous medical and personal burden on postmenopausal women. In many respects, this is a quality of life issue, she noted.

In a separate analysis presented at this meeting, researchers also reported greater response rates for BMD at three combined anatomical sites (total hip, femoral neck, and lumbar spine) in women with postmenopausal osteoporosis who were treated with abaloparatide vs placebo or teriparatide at 6, 12, and 18 months.

Broken bones due to osteoporosis are increasingly common in postmenopausal women and represent a severe public health crisis worldwide, according to President and CEO at Radius Health Robert Ward. He said it is hoped this new agent may be able to help lower morbidity and mortality associated with postmenopausal osteoporosis.

Abaloparatide is an osteoanabolic analog of parathyroid hormone-related protein (PTHrP). Currently, it is in development for potential use as a daily self-administered injection for the treatment of postmenopausal osteoporosis. Radius Health is also developing the investigational abaloparatide-transdermal for potential use as a short wear-time transdermal patch.

References

1. Fitzpatrick L, et al. Abstract 1053: Effects of Abaloparatide on Major Osteoporotic Fracture Incidence in Postmenopausal Women with Osteoporosis – Results of the Phase 3 ACTIVE Trial.
2. Hattersley G, et al. Abstract FR0333: Response Rates for Hip, Femoral Neck and Lumbar Spine BMD are Higher for Patients Treated with Abaloparatide when Compared to Placebo or Teriparatide – Results of the ACTIVE Trial. Both presented at: American Society for Bone and Mineral Research (ASBMR) 2015 Annual Meeting; Oct. 9-12, 2015; Seattle.