Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
Asundexian demonstrated a moderate benefit in reducing ischemic stroke compared to placebo in the OCEANIC-STROKE trial, with a csHR of 0.74 (95% CI 0.65Ð0.84) and a statistically significant p-value (<0.001). However, the early efficacy endpoint at 90 days did not reach statistical significance (p=0.08), indicating some limitations in the evidence. Overall, the evidence supports a moderate therapeutic impact.
Cost effectiveness
There is no available cost-effectiveness analysis or ICER data for asundexian, as it is still investigational and not approved. The lack of any economic model or cost data leads to a conclusion of non-cost-effectiveness.
Quality of life
While the EQ-5D instrument is planned for use in the OCEANIC-STROKE trial, no results or utility values are publicly available. This absence of data limits the ability to assess the impact on HRQoL, leading to a rating of no demonstrated benefit.
Supporting Domains
Safety and Adverse Effects
The safety profile of asundexian appears acceptable, with ISTH major bleeding rates being similar between asundexian and placebo (1.9% vs 1.7%). The trial design and reporting align with expectations for safety assessments, although broader adverse event profiles are not fully reported.
Comparator Selection
Asundexian was compared to placebo in the context of standard antiplatelet therapy, which is appropriate for assessing its incremental benefit. This aligns well with current clinical guidelines for secondary stroke prevention.
Patient Population and Subgroups
The OCEANIC-STROKE trial included a large and diverse population (N=12,327) with relevant demographics for the intended patient population. However, some limitations exist regarding specific country-level representation.
Care Pathway Integration
Asundexian is designed to be an add-on therapy to existing antiplatelet treatments, which suggests a good fit within current clinical pathways. The trial’s design indicates that it can be integrated with minimal disruption.
Resource Use and Cost Implications
No data on resource use or cost implications are available, as asundexian is not yet approved. The absence of any economic analysis or cost data leads to a conclusion of unsustainable budget impact.
Evidence Quality and Robustness
The evidence is primarily derived from a large phase III RCT (OCEANIC-STROKE), which is robust in design. However, the public reporting is limited to conference slides, which constrains the assessment of bias and completeness.
Uncertainty, Sensitivity, and Broader Impacts
There are significant uncertainties due to the lack of real-world evidence and economic data. While the clinical data is strong, the absence of broader impact assessments and economic modeling raises concerns about the overall decision-making context.
