Postmenopausal women at high or very high risk of fracture gained significantly more bone mineral density and were significantly less likely to experience a fracture when taking abaloparatide for 18 months, according to new research presented at the hybrid annual meeting of the North American Menopause Society.
“The findings showed that abaloparatide was better than teriparatide in a number of parameters important in osteoporosis treatment, and similar in others, in high-risk and very-high-risk postmenopausal women with osteoporosis,” Bart Clarke, MD, a professor of medicine at Mayo Clinic in Rochester, Minn., said in an interview. “Abaloparatide is safe and effective for use in high-risk or very-high-risk postmenopausal women,” as defined by the new American Association of Clinical Endocrinology/American College of Endocrinology osteoporosis guidelines.
Ricardo R. Correa, MD, of the department of endocrinology and director of diversity for graduate medical education at the University of Arizona, Phoenix, said that the study demonstrates that abaloparatide and teriparatide have a very similar effect with abaloparatide providing a slightly better absolute risk reduction in fracture. Dr. Correa was not involved in the research.
“What will drive my decision in what to prescribe will be the cost and insurance coverage,” Dr. Correa said. “At the Veterans Administration hospital, the option that we have is abaloparatide, so this is the option that we use.”
Among women at least 65 years old who have already had one fracture, 1 in 10 will experience another fracture within the next year, and 30% will have another fracture within the next 5 years, the authors noted in their background material. Since phase 3 ACTIVE study data in 2016 showed that abaloparatide reduces fracture risk while increasing bone mineral density, compared with placebo, the researchers reanalyzed that data to assess the drug’s efficacy in patients at high or very high risk for fracture.
The study involved 2,463 postmenopausal women with osteoporosis who received one of three interventions: 80 mcg abaloparatide daily, placebo, or 20 mcg subcutaneous teriparatide daily. Only the abaloparatide and placebo groups were double blinded.
“Teriparatide was used as the comparator drug because teriparatide was previously approved as the first anabolic drug for osteoporosis,” Dr. Clarke said in an interview. “The hope was to show that abaloparatide was a better anabolic drug.”
Women were considered at high or very high risk of fracture if they met at least one of the following four criteria from the 2020 American Association of Clinical Endocrinology guidelines:
- Fracture within the past 12 months or prevalent vertebral fracture.
- Very low T-score (less than –3.0) at baseline at any site.
- Multiple fractures at baseline since age 45.
- Very high fracture risk based on the Fracture Risk Assessment Tool (FRAX) (at least 30% for major osteoporotic fracture or at least 4.5% for hip fracture).
Among the 2,026 patients who met at least one of these criteria, 664 received abaloparatide, 685 received teriparatide, and 677 received placebo. Both the abaloparatide and teriparatide significantly reduced new vertebral fracture risk, compared with placebo. In the abaloparatide group, 0.72% of women had a new vertebral fracture, compared with 0.99% in the teriparatide group and 4.77% in the placebo group (P < .0001).
Abaloparatide and teriparatide also led to significant increases in lumbar spine, total hip, and femoral neck bone mineral density, compared with placebo (P < .0001).
The study was limited by its duration of 18 months and the Food and Drug Administration’s restriction on using abaloparatide for more than 2 years because of the theoretical risk of increasing osteosarcoma, although that risk has never been demonstrated in humans, Dr. Correa said. ”We need more data with abaloparitide in more than 2 years,” he added.
In determining which medication clinicians should first prescribe to manage osteoporosis, Dr. Correa said practitioners should consider the type of osteoporosis women have, their preferences, and their labs on kidney function.
With mild to moderate osteoporosis, bisphosphonates will be the first option while denosumab will be preferred for moderate to severe osteoporosis. Teriparatide and abaloparitide are the first-line options for severe osteoporosis, he said.
“If the glomerular filtration rate is low, we cannot use bisphosphonate and we will have to limit our use to denosumab,” he said. Route and frequency of delivery plays a role in patient preferences.
“If the patient prefers an infusion once a year or a pill, then bisphosphonate,” he said, but “if the patient is fine with an injection every 6 months, then denosumab.” Patients who need and can do an injection every day can take abaloparitide or teriparatide.
Failure of previous treatments also guide clinical decisions, he added. ”If the patient has been on one medication and has a fracture or the bone mineral density decreases, then we need to switch to another medication, usually teriparatide or abaloparitide, to build new bone.”
Contraindications for abaloparatide include a high serum calcium before therapy or prior allergic reactions to components in abaloparatide, Dr. Clarke said. No new safety signals showed up in the data analysis.
The research was funded by Radius Health. Dr. Clarke is an advisory board member of Amgen, and another author consults and speaks for Amgen and is a Radius Health Advisory Board member. Two other authors are Radius Health employees who own stock in the company. Dr Correa has no disclosures.