Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
Evidence from the FREEDOM-2 trial indicates that fedratinib significantly improves spleen volume and symptom response compared to best available therapy, with response rates of 36% and 34% respectively. However, the uncertainty regarding overall survival benefits beyond 6 months limits the rating to moderate benefit.
Cost effectiveness
The cost-effectiveness estimates for fedratinib are within the acceptable range for Healthcare resources, with the EAG’s base-case results indicating an ICER below £30,000 per QALY gained, suggesting it is a cost-effective option.
Quality of life
The evidence suggests that fedratinib improves quality of life through symptom reduction, although the exact utility values were not derived from the recommended EQ-5D-3L. The committee acknowledged that even small symptom reductions can enhance quality of life.
Supporting Domains
Safety and Adverse Effects
Fedratinib has a good safety profile with manageable adverse events. The committee noted that while adverse events exist, they are mostly mild to moderate, indicating acceptable tolerability.
Comparator Selection
The main comparator was best available therapy, which is appropriate. However, the absence of a direct comparison with momelotinib, despite its relevance, limits the robustness of the evidence.
Patient Population and Subgroups
The trial population is representative of the intended patient population with intermediate-2 or high-risk myelofibrosis. The committee noted that the positioning of fedratinib aligns with clinical practice.
Care Pathway Integration
Fedratinib can be integrated into existing treatment pathways with minor adjustments, as it is positioned for use after ruxolitinib and when momelotinib is unsuitable.
Resource Use and Cost Implications
The budget impact is manageable, and the economic model suggests that fedratinib is resource-efficient, aligning with Healthcare funding capabilities.
Evidence Quality and Robustness
The evidence is primarily derived from the FREEDOM-2 trial, a Phase 3 RCT, which provides a strong foundation. However, uncertainties in long-term outcomes introduce some limitations.
Uncertainty, Sensitivity, and Broader Impacts
There are notable uncertainties regarding long-term survival and treatment discontinuation, which could impact the overall assessment of fedratinib’s effectiveness.
