Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The evidence from the HOPE-B trial indicates a moderate benefit of etranacogene dezaparvovec in reducing annualized bleeding rates (ABR) in patients with moderately severe or severe haemophilia B. The trial showed significant reductions in various types of bleeding episodes, with p-values indicating statistical significance. However, the lack of a control arm and the ongoing nature of the trial limit the robustness of the conclusions, leading to a rating of A.
Cost effectiveness
While the treatment has the potential to be cost-effective compared to FIX prophylaxis, the cost-effectiveness estimates are highly uncertain due to the variability in treatment durability. The committee expressed concerns about the long-term cost-effectiveness, leading to a rating of B++.
Quality of life
The committee noted that the treatment could potentially reduce the treatment burden associated with regular FIX prophylaxis, which significantly impacts patients’ quality of life. The potential for fewer hospital visits and better joint health suggests a moderate improvement in HRQoL, although specific validated HRQoL data were not provided.
Supporting Domains
Safety and Adverse Effects
The safety profile of etranacogene dezaparvovec appears acceptable, with manageable adverse events reported. The committee noted that the treatment does not have a history of severe adverse effects compared to existing therapies, supporting a rating of A.
Comparator Selection
The treatment was compared against appropriate standard-of-care alternatives, specifically various FIX prophylaxis treatments. The committee concluded that FIX prophylaxis was the most appropriate comparator, justifying a rating of A+.
Patient Population and Subgroups
The trial population included adult males with moderately severe or severe haemophilia B, which is representative of the intended patient population. However, the exclusion of women and certain patient groups limits generalizability slightly, leading to a rating of A.
Care Pathway Integration
The treatment can be integrated into existing care pathways with minor adjustments, as it primarily replaces existing FIX prophylaxis treatments. The committee noted that the integration would require some planning but is manageable, justifying a rating of A+.
Resource Use and Cost Implications
The treatment is expected to have a high resource burden due to its high cost, which raises concerns about affordability. The committee noted that while it could lead to long-term savings, the initial costs are significant, leading to a rating of B++.
Evidence Quality and Robustness
The evidence base is primarily derived from the HOPE-B trial, which is ongoing and has limitations such as the lack of a control group. The committee expressed concerns about the robustness of the evidence, leading to a rating of B++.
Uncertainty, Sensitivity, and Broader Impacts
There is significant uncertainty regarding the long-term durability of treatment effects and cost-effectiveness. The committee noted that the potential for variability in treatment outcomes could lead to restricted use, justifying a rating of B+.
