Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The clinical trial evidence from the phase 3 AURORA 1 and AURORA 2 trials indicates that voclosporin with mycophenolate mofetil is more effective at stopping lupus nephritis from worsening compared to mycophenolate mofetil alone. The primary endpoint of complete renal response was significantly higher for voclosporin (40.8%) compared to placebo (22.5%). This suggests a clear clinical advantage, although the evidence is based on indirect comparisons with other immunosuppressants.
Cost effectiveness
The cost-effectiveness estimates for voclosporin with mycophenolate mofetil are within what NICE considers acceptable for Healthcare resources. The committee concluded that the ICERs were plausible and sufficiently low, indicating that the treatment is likely to be cost-effective, especially considering the potential benefits of lower steroid doses.
Quality of life
While specific HRQoL data is not extensively detailed, the document discusses the significant impact of lupus nephritis on patients’ daily lives and mental well-being. The potential for voclosporin to reduce the need for higher doses of steroids, which have adverse effects, suggests a moderate improvement in quality of life, although direct evidence from validated tools is limited.
Supporting Domains
Safety and Adverse Effects
Voclosporin is noted to have a good safety profile, with manageable adverse effects compared to existing treatments. The document highlights concerns about current treatments causing significant side effects, suggesting that voclosporin may offer a safer alternative, although specific adverse event data is not extensively detailed.
Comparator Selection
The treatment was compared against mycophenolate mofetil, which is a relevant standard of care for lupus nephritis. The committee noted that while there are other immunosuppressants, the choice of mycophenolate mofetil as a comparator is appropriate given its common use in clinical practice.
Patient Population and Subgroups
The AURORA trials included a diverse patient population, although there were concerns about generalizability to the UK population due to the absence of UK participants. However, clinical experts indicated that the trial population is reflective of the Healthcare population, suggesting moderate representativeness.
Care Pathway Integration
Voclosporin is intended to be used as an add-on treatment to existing therapies, which suggests a good fit within current treatment pathways. Minor adjustments may be needed for its integration, but overall, it is expected to be manageable within existing clinical practices.
Resource Use and Cost Implications
The document indicates that the budget impact of voclosporin is manageable and aligns with Healthcare planning. The potential for reduced steroid use may also lead to lower overall healthcare costs, supporting its economic viability.
Evidence Quality and Robustness
The evidence is primarily derived from phase 3 RCTs, which are considered robust. However, there are some limitations noted, such as attrition bias and the generalizability of the trial results, which slightly affect the overall robustness of the evidence.
Uncertainty, Sensitivity, and Broader Impacts
While there are uncertainties regarding long-term treatment effects and the extrapolation of short-term data, the committee acknowledged that the treatment addresses a significant unmet need in lupus nephritis, which mitigates some of the concerns about uncertainty.
