Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The clinical evidence for belumosudil comes from two phase 2 trials (ROCKstar and KD025-208) that suggest it improves symptoms in patients with chronic graft-versus-host disease (GVHD). However, it was not compared directly with the best available therapy, and the evidence is primarily indirect. The committee noted that while the overall response rate was estimated at 73.1%, the lack of direct comparison with standard treatments limits the strength of the evidence.
Cost effectiveness
The cost-effectiveness estimates for belumosudil are uncertain but likely fall within the acceptable range for Healthcare resources. The committee concluded that the most likely ICERs indicated that belumosudil was a cost-effective option compared to best available therapy, although uncertainties remain.
Quality of life
The committee acknowledged that chronic GVHD significantly impacts quality of life, and the introduction of an oral treatment like belumosudil could alleviate some burdens associated with existing therapies. However, specific HRQoL data from the trials were not robustly presented, leading to a moderate rating.
Supporting Domains
Safety and Adverse Effects
Belumosudil has a favorable safety profile with mostly mild to moderate adverse events reported in the trials. The committee noted that serious adverse events were rare, indicating good tolerability compared to existing therapies.
Comparator Selection
The trials did not include a direct comparison with the best available therapy, which is a significant limitation. The committee relied on indirect comparisons, which introduces uncertainty regarding the relative effectiveness of belumosudil versus established treatments.
Patient Population and Subgroups
The trials primarily included adults, with no data for the 12-18 age group, which raises concerns about generalizability. While the committee acknowledged the biological plausibility of efficacy in younger patients, the lack of direct evidence limits confidence in the findings.
Care Pathway Integration
Belumosudil can be integrated into existing care pathways with minor adjustments, as it is an oral therapy that could replace more burdensome treatments like extracorporeal photopheresis. The committee noted that this could improve patient adherence and access to treatment.
Resource Use and Cost Implications
The resource implications of adopting belumosudil are manageable, with the potential for cost savings compared to existing therapies. The committee recognized that the oral administration could reduce healthcare resource utilization associated with travel and hospital visits.
Evidence Quality and Robustness
The evidence base is primarily derived from phase 2 trials, which are less robust than phase 3 studies. While the trials were well-conducted, the lack of direct comparative data and the reliance on indirect evidence introduce significant uncertainty.
Uncertainty, Sensitivity, and Broader Impacts
There is considerable uncertainty surrounding the cost-effectiveness estimates and the long-term outcomes associated with belumosudil. The committee noted that while the treatment addresses a significant unmet need, the uncertainties could restrict its use in certain contexts.
