Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
Ravulizumab was shown to be similarly effective as eculizumab based on data from two non-inferiority phase 3 trials. However, the trials did not demonstrate statistically significant differences in clinical outcomes, leading to the conclusion that ravulizumab and eculizumab have comparable efficacy.
Cost effectiveness
Ravulizumab is considered a cost-effective option compared to eculizumab, as it is more effective and less costly in all scenario analyses presented, especially when accounting for the confidential discount provided by the company.
Quality of life
The evidence suggests that ravulizumab improves quality of life due to less frequent infusions compared to eculizumab, which is supported by patient surveys indicating better independence and reduced treatment burden. However, the statistical significance of these improvements was not established.
Supporting Domains
Safety and Adverse Effects
The safety profile of ravulizumab is reported to be similar to that of eculizumab, with no significant differences in adverse events noted in the trials. This indicates a very good tolerability for ravulizumab.
Comparator Selection
The trials compared ravulizumab directly with eculizumab, which is the standard of care for paroxysmal nocturnal haemoglobinuria, providing a strong basis for the evaluation of its effectiveness.
Patient Population and Subgroups
The trial populations were deemed generalizable to the clinical practice in England, and the committee acknowledged that the effectiveness of ravulizumab is maintained across the intended patient population.
Care Pathway Integration
Ravulizumab can be integrated into existing care pathways with minimal adjustments, as it is administered less frequently than eculizumab, which aligns well with current clinical practices.
Resource Use and Cost Implications
The economic model indicates that ravulizumab has a manageable budget impact and is resource-efficient, particularly due to the reduced frequency of administration compared to eculizumab.
Evidence Quality and Robustness
The evidence is based on two phase 3 trials with a robust design, although there are some limitations regarding the statistical significance of the outcomes. Overall, the evidence is credible and supports the conclusions drawn.
Uncertainty, Sensitivity, and Broader Impacts
While there are some uncertainties regarding the long-term effectiveness and the generalizability of trial results, the committee found that these were manageable and did not significantly undermine the overall assessment.
