Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The ACTIVE trial demonstrated that abaloparatide significantly reduced the risk of new vertebral fractures by 88% compared to placebo, which indicates a moderate benefit over current care. However, the results for non-vertebral fractures were not statistically significant, and the comparison with teriparatide was also non-significant, leading to a moderate rating.
Cost effectiveness
The cost-effectiveness estimates for abaloparatide are within the range that NICE considers acceptable for Healthcare resources. The committee concluded that the most likely cost-effectiveness estimates were favorable, indicating a clear cost-effective profile under common thresholds.
Quality of life
The committee noted that osteoporosis significantly affects quality of life, and abaloparatide is expected to improve this by reducing fracture risk. The evidence suggests moderate improvements in HRQoL, particularly for those at very high risk of fractures, though specific validated tools were not detailed.
Supporting Domains
Safety and Adverse Effects
Abaloparatide has a safety profile similar to existing treatments, with a lower risk of hypercalcemia compared to teriparatide and no observed cases of osteonecrosis in the trials. This indicates very good tolerability and a favorable safety profile.
Comparator Selection
The committee confirmed that abaloparatide was positioned against appropriate comparators, specifically romosozumab and teriparatide, which are standard treatments for osteoporosis. This indicates a strong comparator selection.
Patient Population and Subgroups
The trial population included women after menopause with osteoporosis, and the committee noted that the results were broadly generalizable to the intended patient population, including trans men and non-binary individuals. However, there were some concerns about the representativeness of the very high-risk subgroup.
Care Pathway Integration
Abaloparatide can be integrated into existing treatment pathways with minimal adjustments, as it is used in the same treatment context as other anabolic treatments. The committee noted that it does not require new infrastructure or significant changes to current practices.
Resource Use and Cost Implications
The economic model indicated that the resource implications of implementing abaloparatide are manageable and aligned with Healthcare planning. The committee concluded that the budget impact was justifiable given the expected health benefits.
Evidence Quality and Robustness
The evidence base is supported by a robust RCT (ACTIVE trial) and a long-term extension study (ACTIVExtend), although there are some uncertainties regarding generalizability to the very high-risk population. Overall, the evidence quality is acceptable with some methodological concerns.
Uncertainty, Sensitivity, and Broader Impacts
While there are uncertainties in the treatment effects and cost-effectiveness estimates, the committee noted that these were manageable and did not significantly undermine the overall positive assessment of abaloparatide. The context of unmet need also supports its use.
