Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
Ravulizumab has shown clinical effectiveness in treating atypical haemolytic uraemic syndrome (aHUS) based on two open-label single-arm studies. However, there is no direct comparative data with eculizumab, the current standard of care. The committee noted that while the evidence suggests ravulizumab is effective, the lack of direct comparisons introduces uncertainty regarding its relative efficacy.
Cost effectiveness
Ravulizumab is considered cost-effective compared to eculizumab, with the committee noting that the cost-effectiveness estimates fall within acceptable thresholds for Healthcare resources. The economic model presented by the company was deemed suitable for decision-making, supporting the conclusion of cost-effectiveness.
Quality of life
The committee concluded that ravulizumab improves quality of life due to its less frequent dosing schedule compared to eculizumab, which requires infusions every two weeks. This reduction in treatment burden is expected to enhance patients’ ability to work and engage in social activities, leading to strong quality-of-life gains.
Supporting Domains
Safety and Adverse Effects
The committee noted that adverse events for ravulizumab are likely to be similar to those of eculizumab, with no significant safety concerns raised in the trials. Although there were some deaths reported in the trials, these were attributed to patients not representative of the typical aHUS population, suggesting an acceptable safety profile.
Comparator Selection
The evidence for ravulizumab was derived from single-arm studies without direct comparisons to eculizumab. While indirect comparisons were made, the committee acknowledged the uncertainty surrounding these comparisons, leading to a rating of B++ for comparator selection.
Patient Population and Subgroups
The trial populations included a range of patients with aHUS, although there were concerns about the generalizability of the results to the UK population. The committee concluded that the evidence was moderately representative, with some limitations in subgroup exploration.
Care Pathway Integration
Ravulizumab can be integrated into existing care pathways with minor adjustments, primarily due to its less frequent dosing schedule. This integration is manageable within current clinical practices, supporting a rating of A+.
Resource Use and Cost Implications
The economic model indicated that ravulizumab would not impose a significant resource burden on the Healthcare, with the potential for cost savings due to its lower acquisition cost compared to eculizumab. This supports a rating of A for resource use and cost implications.
Evidence Quality and Robustness
While the evidence base includes two single-arm studies, the lack of direct comparative data and the potential biases in the trial design raise concerns about the robustness of the evidence. Therefore, a rating of B++ is appropriate.
Uncertainty, Sensitivity, and Broader Impacts
There are notable uncertainties regarding the long-term safety and efficacy of ravulizumab, particularly due to the reliance on indirect comparisons and assumptions made in the economic model. This uncertainty, coupled with the potential impact of future biosimilars, justifies a rating of B+.
