New PBS-Listed Option for Severe Osteoporosis: Abaloparatide

Abaloparatide is now listed on the Pharmaceutical Benefits Scheme (PBS) for severe osteoporosis in both first-line and second-line settings.

Abaloparatide acts as an agonist at the parathyroid hormone receptor 1 (PTHR1) to stimulate osteoblast activity. As it promotes new bone formation, abaloparatide is classified as an anabolic osteoporosis therapy. In comparison, antiresorptive medications (such as bisphosphonates) primarily slow bone resorption. For patients at very high fracture risk, the early use of anabolic therapy is increasingly recognised as an effective strategy to rapidly improve bone strength and reduce fracture risk.

The phase 3 ACTIVE trial randomised 2,463 postmenopausal women with osteoporosis to receive daily subcutaneous abaloparatide, teriparatide, or placebo for 18 months. Abaloparatide significantly reduced the incidence of new vertebral fractures compared with placebo (0.6% vs 4.2%), as well as nonvertebral fractures (2.7% vs 4.7%). In addition, abaloparatide was associated with increases in bone mineral density (BMD) at the lumbar spine, total hip, and femoral neck. Gains in BMD were significantly greater than those seen with teriparatide at the total hip and femoral neck at all time points studied. Abaloparatide was generally well tolerated, with rates of serious adverse events similar to placebo and teriparatide. The incidence of hypercalcaemia was significantly lower with abaloparatide than with teriparatide (3.4% vs 6.4%).

Abaloparatide is administered as a once-daily subcutaneous injection. Treatment is limited to a maximum duration of 18 months as animal studies indicate an increased risk of osteosarcoma with prolonged exposure. While the relevance of these findings to humans is uncertain, abaloparatide is contraindicated in patients with a known risk of osteosarcoma. As with other anabolic osteoporosis therapies, treatment may be followed by an antiresorptive agent to maintain BMD gains and sustain fracture risk reduction.