Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The ELATIVE trial, a Phase 3 randomized controlled trial, demonstrated that 50.9% of patients receiving elafibranor achieved cholestasis response at week 52 compared to only 3.8% in the placebo group (p<0.0001). This indicates a moderate benefit over current care, although the lack of direct comparison with obeticholic acid introduces some uncertainty regarding its relative effectiveness.
Cost effectiveness
The cost-effectiveness estimates for elafibranor are within the range that NICE considers acceptable, even with uncertainties in the economic model. The committee concluded that the most plausible ICER was aligned with the EAG base case, indicating marginal cost-effectiveness.
Quality of life
While the ELATIVE trial collected EQ-5D-5L quality-of-life data, the company deemed it unreliable due to small sample sizes and opted to use literature values instead. This raises concerns about the robustness of the HRQoL data, leading to a minimal or mixed impact on quality of life.
Supporting Domains
Safety and Adverse Effects
Elafibranor has a very good safety profile, with adverse events primarily being mild or moderate. The committee noted that elafibranor does not worsen itching, which is a significant concern with obeticholic acid, indicating a favorable tolerability compared to existing treatments.
Comparator Selection
The main comparator for elafibranor is obeticholic acid, which is appropriate given its use in similar patient populations. However, the absence of direct head-to-head trials and reliance on indirect comparisons introduces some limitations in the evidence base.
Patient Population and Subgroups
The ELATIVE trial included a representative sample of patients aged 18 to 75 years with primary biliary cholangitis who had inadequate responses to UDCA or were intolerant to it. This broad inclusion supports generalizability to the intended patient population.
Care Pathway Integration
Elafibranor can be integrated into existing treatment pathways with minimal adjustments, as it is recommended for use in patients who do not respond to or cannot tolerate UDCA. This facilitates its adoption in clinical practice.
Resource Use and Cost Implications
The economic model indicates that elafibranor is likely to be resource-efficient, with manageable budget impacts aligned with Healthcare planning. The committee noted that the cost-effectiveness estimates were acceptable, supporting its use.
Evidence Quality and Robustness
The evidence base is primarily supported by the Phase 3 ELATIVE trial, which is robust despite some methodological concerns regarding the NMA. The committee found the evidence sufficient for decision-making, although some uncertainties remain.
Uncertainty, Sensitivity, and Broader Impacts
There are significant uncertainties regarding the long-term efficacy of elafibranor and the relationship between surrogate outcomes and actual clinical benefits. The committee acknowledged these uncertainties but noted that they did not preclude a recommendation.
