Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
Roxadustat demonstrated non-inferiority to darbepoetin alfa in the DOLOMITES trial, which is a Phase 3 study. The primary endpoint was met, showing a 12% difference in Hb response rates, indicating moderate benefit over current care. However, the lack of superiority and the exclusion of certain populations limit the strength of the evidence.
Cost effectiveness
The cost-effectiveness estimates for Roxadustat are within NICE’s acceptable thresholds, indicating it is clearly cost-effective under common thresholds. The economic model reflects the treatment’s impact on quality-adjusted life years (QALYs) and is acceptable for decision-making.
Quality of life
The DOLOMITES trial included health-related quality of life measures such as the SF-36 and EQ-5D-5L, which showed non-inferiority for Roxadustat compared to darbepoetin alfa. This suggests moderate improvements in quality of life, although the evidence is primarily based on secondary endpoints.
Supporting Domains
Safety and Adverse Effects
Roxadustat has an acceptable safety profile, with adverse events reported being manageable. The committee noted that while there are some concerns regarding cardiovascular risks, the overall tolerability is good compared to existing therapies.
Comparator Selection
The DOLOMITES trial provided a direct comparison with darbepoetin alfa, which is a key alternative treatment. This head-to-head comparison strengthens the evidence base, although some limitations exist regarding the generalizability of the trial population.
Patient Population and Subgroups
The trial population in DOLOMITES included adults with symptomatic anaemia and stage 3 to 5 CKD, which is representative of the intended patient population. However, the exclusion of certain subgroups may limit generalizability.
Care Pathway Integration
Roxadustat can be integrated into existing care pathways with minor adjustments, as it offers an oral alternative to injectable ESAs. This is particularly beneficial for patients who have difficulty with injections.
Resource Use and Cost Implications
The budget impact of Roxadustat is manageable, and the economic model suggests that it is resource-efficient. The commercial arrangement further supports its affordability within the Healthcare.
Evidence Quality and Robustness
The evidence base is primarily derived from the DOLOMITES trial, which is a robust Phase 3 RCT. However, concerns regarding the pooling of data and the exclusion of certain populations introduce some methodological limitations.
Uncertainty, Sensitivity, and Broader Impacts
While there are uncertainties regarding long-term outcomes and the impact of Hb levels above 120 g/L, the overall context is favorable, and the committee is willing to accept some uncertainty for this appraisal.
