Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
Foslevodopa-foscarbidopa shows moderate benefit over standard care, with a significant improvement in ‘on’ time without troublesome dyskinesia and a reduction in ‘off’ time. The primary endpoint of the phase 3 trial M15-736 demonstrated a clinically significant improvement of 1.75 hours in ‘on’ time and 1.79 hours in ‘off’ time compared to oral levodopa-carbidopa. However, the uncertainty regarding its effectiveness in patients who cannot have apomorphine limits the strength of the evidence.
Cost effectiveness
The cost-effectiveness estimates for foslevodopa-foscarbidopa are within the range that NICE considers acceptable, particularly when compared to standard care. The committee noted that the ICERs were likely to be at the lower end of the acceptable range, suggesting a defensible economic value.
Quality of life
The treatment is likely to improve quality of life, particularly related to sleep and daily functioning, as indicated by patient expert testimonies. However, the exact benefits related to sleep were not adequately captured in the economic modelling, leading to some uncertainty.
Supporting Domains
Safety and Adverse Effects
Foslevodopa-foscarbidopa has a very good safety profile, with mostly mild or moderate adverse events reported. Serious adverse events were rare, indicating a favorable tolerability compared to existing therapies.
Comparator Selection
The treatment was primarily compared to standard care and levodopa-carbidopa intestinal gel, which are appropriate comparators. However, the exclusion of patients who could have apomorphine or deep brain stimulation limits the robustness of the comparisons.
Patient Population and Subgroups
The population considered for the evaluation is narrower than the marketing authorization, focusing on those who cannot have apomorphine or deep brain stimulation. This raises concerns about generalizability, although it reflects a high unmet need.
Care Pathway Integration
Foslevodopa-foscarbidopa can be integrated into existing care pathways with minor adjustments, as it is delivered via a subcutaneous infusion that is simpler than some existing treatments.
Resource Use and Cost Implications
The treatment is expected to have a manageable budget impact, with potential cost savings associated with improved management of Parkinson’s symptoms and reduced need for other treatments.
Evidence Quality and Robustness
The evidence base includes a phase 3 RCT (M15-736) and supporting studies, although there are some concerns regarding the generalizability of the trial population and the potential for unblinding.
Uncertainty, Sensitivity, and Broader Impacts
There are several uncertainties regarding the ICERs, the effectiveness in the narrower population, and the potential benefits not captured in the modelling. This leads to a moderate level of uncertainty in the overall assessment.
