Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The evidence from the OASIS-HAE phase 3 trial shows a moderate benefit with donidalorsen, demonstrating a significant reduction in attack rates compared to placebo (81% reduction for q4wks and 55% for q8wks). However, the absence of active comparator data limits the strength of the claim for superiority over existing treatments.
Cost effectiveness
No cost-effectiveness data, ICER estimates, or QALY gains are available in the document. The NICE appraisal is still in progress, indicating a lack of economic evaluation necessary for assessing cost-effectiveness.
Quality of life
The OASIS-HAE trial reported significant improvements in quality of life measures, specifically the AE-QoL score, with a mean change of 18.6 points versus placebo. This indicates a moderate but meaningful improvement in patient-reported outcomes.
Supporting Domains
Safety and Adverse Effects
The safety profile from the OASIS-HAE trial indicates a very good tolerability with 73% of patients experiencing any adverse event, mostly mild to moderate. Serious adverse events were rare, suggesting a favorable safety profile compared to placebo.
Comparator Selection
The pivotal trial used placebo as a comparator, which is standard for establishing efficacy but does not provide evidence of comparative effectiveness against active prophylaxis options. This limits the robustness of the evidence.
Patient Population and Subgroups
The trial population included patients aged 12 and older with hereditary angioedema, aligning with the intended use. However, there are concerns about racial diversity, as the majority of participants were White, which may limit generalizability.
Care Pathway Integration
The treatment can be integrated into existing care pathways with minor adjustments, such as training for self-administration. The FDA label indicates it is intended for self-administration, which supports ease of integration.
Resource Use and Cost Implications
There is insufficient data on resource use and cost implications, with only a list price reported and no detailed economic analysis provided. This raises concerns about the broader financial impact of the therapy.
Evidence Quality and Robustness
The evidence is primarily based on a phase 3 RCT, which is a strong design. However, the reliance on open-label extension data and the absence of active comparator trials introduce some limitations in robustness.
Uncertainty, Sensitivity, and Broader Impacts
There is significant uncertainty regarding the long-term effectiveness and safety due to the lack of real-world data and the ongoing NICE appraisal. This uncertainty may affect the decision-making process.
