Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
Burosumab demonstrates moderate clinical effectiveness by significantly increasing serum phosphate levels compared to placebo, with 94.1% of patients achieving normal phosphate levels. However, the evidence for improvements in patient-reported outcomes such as pain and fatigue is uncertain and primarily based on short-term data.
Cost effectiveness
The cost-effectiveness estimates for burosumab fall within the acceptable range for Healthcare resources, with an ICER around £20,000 to £30,000 per QALY gained. This suggests that the therapy is likely to be a cost-effective option for treating XLH in adults.
Quality of life
The evidence suggests moderate improvements in HRQoL, as indicated by the positive impact on physical functioning and pain reduction. However, the utility values are derived from indirect measures, and the absence of EQ-5D data introduces some uncertainty.
Supporting Domains
Safety and Adverse Effects
Burosumab has a very good safety profile, with mostly mild to moderate adverse events reported. Serious adverse events are rare, indicating that the treatment is well-tolerated compared to conventional therapies.
Comparator Selection
The clinical trials compared burosumab against placebo, which is appropriate given the context of treatment for XLH. However, the lack of direct comparison with conventional treatments limits the robustness of the evidence.
Patient Population and Subgroups
The trial population is representative of the adult XLH population, with relevant subgroups identified. However, there are concerns regarding the generalizability of findings to all adults with XLH due to the narrow focus of the evidence.
Care Pathway Integration
Burosumab can be integrated into existing care pathways with minor adjustments, as it is less burdensome than conventional treatments. This facilitates its adoption in clinical practice.
Resource Use and Cost Implications
The resource implications of burosumab are manageable, with the potential for cost savings in the long term due to reduced complications associated with XLH. The economic model supports this view.
Evidence Quality and Robustness
The evidence base is strong, primarily derived from a Phase 3 RCT, although there are some limitations regarding the generalizability and the reliance on indirect measures for HRQoL.
Uncertainty, Sensitivity, and Broader Impacts
There are notable uncertainties regarding the long-term effects of burosumab, particularly concerning its impact on mortality and the assumptions made in the economic model. These uncertainties may affect the overall decision-making process.
