Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
Avacopan demonstrated a clear clinical advantage in the ADVOCATE trial, showing significant improvement in disease remission rates at both 26 and 52 weeks compared to standard care with prednisone. Specifically, 66% of patients in the avacopan group achieved sustained remission at week 52 compared to 55% in the prednisone group, with a statistically significant p-value of 0.007 for superiority. This evidence supports a strong therapeutic impact relative to current standards.
Cost effectiveness
The cost-effectiveness estimates for avacopan with standard care are within the range that NICE considers acceptable for Healthcare resources. The committee concluded that the most plausible ICER falls within the £20,000 to £30,000 per QALY gained range, indicating a clear cost-effective use of resources.
Quality of life
The evidence suggests that avacopan reduces corticosteroid toxicity, which is associated with significant side effects that negatively impact HRQoL. The trial data indicate a reduction in the Corticosteroid Toxicity Index, suggesting improvements in patient well-being, although specific validated HRQoL measures were not detailed in the document.
Supporting Domains
Safety and Adverse Effects
Avacopan has a very good safety profile, with reduced corticosteroid use leading to lower toxicity. The trial indicated a significant reduction in the mean Corticosteroid Toxicity Index in the avacopan group compared to the prednisone group, suggesting that avacopan is associated with fewer adverse effects.
Comparator Selection
The clinical trials compared avacopan against appropriate standard care options, specifically cyclophosphamide or rituximab with corticosteroids, which are the established treatments for severe GPA and MPA. This ensures that the evidence is relevant and applicable to the intended patient population.
Patient Population and Subgroups
The trial population included patients with severe active GPA or MPA, which aligns with the intended use of avacopan. While the population is representative, there may be some limitations in subgroup analyses that were not fully explored.
Care Pathway Integration
Avacopan can be integrated into existing treatment pathways with minor adjustments, as it is recommended to be used alongside standard care regimens. This suggests that the integration into clinical practice would be manageable without significant disruption.
Resource Use and Cost Implications
The economic model indicates that avacopan is likely to be resource-efficient, with a manageable budget impact. The committee noted that the model’s assumptions were conservative, suggesting that the actual resource use may be lower than estimated.
Evidence Quality and Robustness
The evidence is based on a robust Phase 3 RCT (ADVOCATE) with a well-defined methodology and low risk of bias. The trial’s findings are supported by additional data on corticosteroid toxicity, enhancing the credibility of the evidence base.
Uncertainty, Sensitivity, and Broader Impacts
While there are some uncertainties regarding the economic model and assumptions, the committee concluded that these uncertainties are manageable and do not significantly undermine the overall positive assessment of avacopan’s value.
