Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The evidence from the KALM trials indicates that difelikefalin provides a moderate benefit in reducing itch severity compared to placebo, with significant improvements observed in the primary outcome measure (WI-NRS). The odds ratios suggest a clear therapeutic effect, although there is some uncertainty regarding the long-term efficacy and the impact of concurrent anti-itch treatments.
Cost effectiveness
The cost-effectiveness estimates for difelikefalin fall within the acceptable range for Healthcare resources, with an ICER of £22,000 per QALY gained. This suggests that the treatment is a good value for the benefits it provides, especially considering the discount offered.
Quality of life
While difelikefalin shows some potential to improve quality of life by reducing pruritus, the evidence regarding its impact on HRQoL is uncertain. The committee noted that the improvement in quality of life was not clearly established, indicating a mixed impact.
Supporting Domains
Safety and Adverse Effects
Difelikefalin has an acceptable safety profile, with adverse events primarily being mild to moderate. The trials did not report any severe adverse effects that would undermine the overall value of the treatment.
Comparator Selection
The treatment was compared against placebo in the KALM trials, which is appropriate given the lack of established standard care for CKD-aP. The inclusion of additional anti-itch medications in the comparator group reflects real-world practice, enhancing the relevance of the findings.
Patient Population and Subgroups
The KALM trials included a diverse patient population with moderate to severe CKD-aP, and subgroup analyses were conducted. However, there are some concerns regarding the representativeness of the trial population compared to the broader UK population.
Care Pathway Integration
Difelikefalin can be integrated into existing care pathways with minor adjustments, as it is administered concurrently with dialysis. This minimizes disruption and aligns with current clinical practices.
Resource Use and Cost Implications
The budget impact of difelikefalin is manageable, especially considering the potential reduction in treatment burden for patients. The economic model suggests that the resource implications are justifiable given the benefits.
Evidence Quality and Robustness
The evidence is based on two Phase 3 RCTs, which provide a strong foundation for the efficacy claims. However, there are some methodological concerns regarding the pooling of data and handling of missing data that introduce uncertainty.
Uncertainty, Sensitivity, and Broader Impacts
There are notable uncertainties regarding the long-term efficacy of difelikefalin and the impact of concurrent treatments. While the treatment addresses an unmet need, the uncertainties may limit its broader acceptance.
