Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The clinical trial evidence from the PROTECT study demonstrates that sparsentan significantly reduces proteinuria compared to irbesartan, with a geometric least squares mean percent change from baseline of -49.8% for sparsentan versus -15.1% for irbesartan at week 36. This indicates a clear clinical advantage, although there is some uncertainty regarding long-term kidney function outcomes.
Cost effectiveness
The cost-effectiveness estimates for sparsentan are within the range that NICE considers acceptable, with an ICER around £20,000 per QALY gained. This indicates that sparsentan is marginally cost-effective, especially considering the significant unmet need in treating IgAN.
Quality of life
While the model primarily considers CKD stage for HRQoL, patient experts highlighted that sparsentan’s ability to reduce proteinuria could lead to improvements in physical symptoms and psychological distress. This suggests moderate improvements in HRQoL, although specific validated tools were not used to quantify these benefits.
Supporting Domains
Safety and Adverse Effects
Sparsentan has a comparable safety profile to irbesartan, with treatment-emergent adverse events leading to discontinuation in 10% of patients compared to 9% for irbesartan. The adverse events reported were mostly manageable, indicating a very good tolerability.
Comparator Selection
Irbesartan is an appropriate comparator as it represents standard RASi therapy commonly used in the NHS. The committee confirmed that it is representative of the treatment landscape for IgAN, thus supporting the validity of the trial comparisons.
Patient Population and Subgroups
The trial population in PROTECT included adults with biopsy-confirmed primary IgAN, which is representative of the intended patient population. However, there were some limitations in subgroup analyses, particularly regarding the use of concomitant treatments.
Care Pathway Integration
Sparsentan can be integrated into existing care pathways with minor adjustments, as it is expected to replace traditional RASi therapy. The committee noted that the treatment aligns well with current clinical practice guidelines.
Resource Use and Cost Implications
The economic model indicates that sparsentan is likely to have a manageable budget impact, especially considering the potential to delay the need for dialysis and transplantation, which are costly interventions.
Evidence Quality and Robustness
The evidence base is supported by a robust Phase 3 RCT (PROTECT) with a well-defined methodology. However, there are some concerns regarding the long-term follow-up and the handling of missing data, which introduces some uncertainty.
Uncertainty, Sensitivity, and Broader Impacts
There are notable uncertainties regarding the long-term effectiveness of sparsentan, particularly in relation to its impact on kidney function and progression to ESRD. The committee expressed concerns about the assumptions made in the economic model and the implications of the stopping rule.
