Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The clinical evidence indicates that pegcetacoplan significantly improves haemoglobin levels compared to eculizumab, with a statistically significant difference of 38.4 g/l at week 16. This suggests a clear clinical advantage over the standard of care, although the evidence for its efficacy against ravulizumab is less robust due to the lack of direct comparison data.
Cost effectiveness
The cost-effectiveness analysis shows that pegcetacoplan is more effective and less costly compared to both eculizumab and ravulizumab, making it a clear cost-effective option under the Healthcare framework.
Quality of life
Patient expert statements indicate that pegcetacoplan has led to fewer blood transfusions and improved fatigue levels, positively impacting quality of life. However, the evidence is primarily anecdotal and lacks robust quantitative measures.
Supporting Domains
Safety and Adverse Effects
The safety profile of pegcetacoplan is acceptable, with manageable adverse events reported. The committee noted that while there may be minor inconveniences related to administration frequency, these are outweighed by the treatment benefits.
Comparator Selection
The primary comparison was made against eculizumab, which is appropriate. However, the lack of direct evidence comparing pegcetacoplan with ravulizumab raises concerns about the robustness of the evidence.
Patient Population and Subgroups
The trial population is representative of the intended patient population with PNH, and the committee found the trial results generalizable to clinical practice in England.
Care Pathway Integration
Pegcetacoplan can be self-administered, which aligns well with current clinical practices and offers greater flexibility compared to existing treatments that require intravenous administration.
Resource Use and Cost Implications
The implementation of pegcetacoplan is expected to lead to cost savings due to reduced need for blood transfusions and the convenience of self-administration, making it a resource-efficient option.
Evidence Quality and Robustness
The evidence is based on a well-structured RCT (PEGASUS trial) with a clear primary endpoint. However, the indirect comparison with ravulizumab introduces some uncertainty.
Uncertainty, Sensitivity, and Broader Impacts
While there are some uncertainties regarding the indirect comparisons, the overall context supports the use of pegcetacoplan, particularly given the unmet need in the PNH population.
