Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The evidence suggests that efanesoctocog alfa may reduce bleeding episodes compared to previous factor VIII replacement therapies, but the clinical effectiveness is uncertain due to limitations in the trial design, including the lack of a control arm and potential biases in intrapatient comparisons. The committee noted that while there were improvements in bleeding rates, the evidence does not clearly demonstrate superiority over existing treatments.
Cost effectiveness
Efanesoctocog alfa is considered a cost-effective use of Healthcare resources based on the economic model, which indicates it is dominant (less costly and more effective) compared to other EHLs and emicizumab in PUPs. The committee concluded that the treatment represents good value, although uncertainties remain in the model inputs.
Quality of life
The trial results indicated improvements in quality of life measures such as Haem-A-QoL and EQ-5D scores, suggesting moderate gains in HRQoL for patients using efanesoctocog alfa. However, the evidence is primarily based on indirect comparisons and may not fully capture the long-term impact on quality of life.
Supporting Domains
Safety and Adverse Effects
The safety profile of efanesoctocog alfa appears acceptable, with mostly mild to moderate adverse events reported. The committee noted that the treatment’s tolerability is comparable to existing therapies, although some concerns about the potential for serious adverse events were acknowledged.
Comparator Selection
The comparators used in the clinical trials included established therapies such as factor VIII replacement and emicizumab. However, the committee noted that there were limitations in the direct comparisons, particularly the absence of a control arm in the main trial, which raises concerns about the robustness of the evidence.
Patient Population and Subgroups
The trial population primarily included patients with severe haemophilia A, which aligns with the marketing authorization. The committee recognized that while the evidence is relevant to the intended population, there are gaps in data for moderate haemophilia A and patients under 2 years.
Care Pathway Integration
Efanesoctocog alfa can be integrated into existing care pathways with manageable adjustments, primarily due to its weekly dosing schedule, which is less burdensome than current therapies. The committee noted that this could improve adherence and overall treatment experience.
Resource Use and Cost Implications
The economic analysis indicates that efanesoctocog alfa is likely to have a manageable budget impact, with potential cost savings associated with reduced bleeding episodes and treatment burden. The committee concluded that the resource implications are favorable.
Evidence Quality and Robustness
While the evidence base includes data from phase 3 trials, there are significant limitations regarding trial design and potential biases. The committee noted that the reliance on indirect comparisons and the absence of a control group in the main trial contribute to uncertainties in the evidence quality.
Uncertainty, Sensitivity, and Broader Impacts
There are notable uncertainties surrounding the clinical effectiveness and cost-effectiveness estimates due to the limitations in trial design and the economic model. The committee acknowledged these uncertainties but considered the treatment’s potential benefits in the context of unmet needs.
