Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
Brolucizumab has been shown to be non-inferior to aflibercept based on the HAWK and HARRIER trials, which demonstrated similar changes in best-corrected visual acuity (BCVA) between the two treatments. However, the lack of a statistically significant difference in BCVA suggests that while brolucizumab is comparable, it does not provide a clear therapeutic advantage over existing options.
Cost effectiveness
Brolucizumab is recommended as a cost-effective option due to its similar or lower total costs compared to aflibercept and ranibizumab, taking into account commercial arrangements. The committee concluded that the cost-comparison criteria were met, indicating a favorable economic evaluation.
Quality of life
The document does not provide specific data on HRQoL improvements associated with brolucizumab. The overall health benefits are stated to be similar to aflibercept and ranibizumab, but without direct evidence of significant HRQoL gains, the impact remains unclear.
Supporting Domains
Safety and Adverse Effects
The safety profile of brolucizumab is reported to be similar to that of aflibercept and ranibizumab, with adverse events being balanced across treatment groups. Although there are risks associated with brolucizumab, such as retinal vasculitis, these are considered rare and do not significantly undermine its overall safety profile.
Comparator Selection
The comparators selected for the appraisal, aflibercept and ranibizumab, are appropriate as they are established treatments for wet age-related macular degeneration. The committee acknowledged that these treatments are the standard of care, ensuring relevant comparisons.
Patient Population and Subgroups
The trials included adults aged 50 years or more with active choroidal neovascularization, which is representative of the intended patient population. However, there may be some limitations in subgroup analyses that could affect generalizability.
Care Pathway Integration
Brolucizumab can be integrated into existing treatment pathways with minor adjustments, as it follows similar administration protocols to aflibercept and ranibizumab. The committee noted that the treatment aligns with current clinical practices.
Resource Use and Cost Implications
The resource implications of brolucizumab are manageable, with the total costs being similar or lower than those of existing treatments. The committee concluded that the economic burden is justifiable given the comparable health benefits.
Evidence Quality and Robustness
The evidence base includes results from two pivotal trials (HAWK and HARRIER) and a network meta-analysis, which provide a robust foundation for the appraisal. However, some methodological concerns were raised regarding the dosing regimens used in the trials.
Uncertainty, Sensitivity, and Broader Impacts
While there are some uncertainties regarding the long-term effectiveness and dosing regimens, the overall context supports the use of brolucizumab, particularly considering the unmet need in treating wet age-related macular degeneration.
