Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The evidence indicates comparable efficacy to existing options, as the pivotal ROCKstar trial demonstrated a 75% overall response rate, but it did not randomize against a standard-of-care control. This limits the certainty of superiority claims. The EMA assessment supports these findings with similar response rates, but the lack of direct comparative data against standard treatments results in a B++ rating.
Cost effectiveness
The NICE appraisal suggests that belumosudil is likely cost-effective, with ICER estimates ranging from £2,976 to £15,226/QALY under various scenarios. Although there is significant uncertainty in the estimates, the overall assessment indicates a defensible position for cost-effectiveness, justifying an A rating.
Quality of life
The primary HRQoL evidence is based on the modified Lee Symptom Scale, which shows some symptomatic benefit, but lacks direct utility measures like EQ-5D. While there are indications of patient-reported improvements, the absence of robust utility data and reliance on symptom scales leads to a B+ rating.
Supporting Domains
Safety and Adverse Effects
Short-term safety data are well characterized, with common adverse events documented. The safety profile appears acceptable, with manageable adverse effects. However, long-term safety remains uncertain due to the non-comparative nature of the data, leading to an A rating.
Comparator Selection
The pivotal study did not compare against standard-of-care treatments but rather between different dosing schedules of belumosudil. While the comparator landscape includes relevant therapies, the lack of direct head-to-head trials against standard care limits the robustness of the evidence, resulting in a B++ rating.
Patient Population and Subgroups
The trial population is representative of the intended patient population with chronic GVHD, and there are analyses of relevant subgroups. The evidence supports the use of belumosudil in heavily pretreated patients, justifying an A+ rating.
Care Pathway Integration
Belumosudil is an oral outpatient therapy, which facilitates integration into existing care pathways. While monitoring requirements exist, the overall integration appears manageable, leading to an A rating.
Resource Use and Cost Implications
The economic implications of belumosudil are significant, with the potential for high resource use due to monitoring and management of interactions. However, the oral administration may reduce some costs associated with infusion therapies. This mixed impact leads to a B+ rating.
Evidence Quality and Robustness
The evidence base includes a pivotal trial and supportive real-world data, but the reliance on non-comparative studies and the absence of randomized controlled trials against standard care introduce uncertainty. This leads to a B++ rating.
Uncertainty, Sensitivity, and Broader Impacts
There is significant uncertainty regarding the comparative effectiveness and cost-effectiveness of belumosudil, particularly due to the variability in ICER estimates. While the treatment addresses an unmet need, the uncertainty surrounding its broader impacts leads to a B+ rating.
