Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The HERO trial provides strong evidence that relugolix is superior to leuprolide in achieving sustained testosterone suppression and reducing the risk of major adverse cardiovascular events (MACE). The trial demonstrated a 96.7% sustained castration rate and a 54% reduction in MACE risk, indicating a clear clinical advantage over the standard of care.
Cost effectiveness
The cost-effectiveness estimates for relugolix are within the acceptable range for Healthcare resources, with ICER values below £20,000 per QALY. This indicates that relugolix is a clearly cost-effective option compared to existing treatments.
Quality of life
The evidence suggests that relugolix, being an oral treatment, may improve quality of life by avoiding the injection-related side effects associated with traditional ADT. While specific HRQoL data is limited, the potential for improved convenience and reduced treatment burden supports a moderate benefit.
Supporting Domains
Safety and Adverse Effects
Relugolix has a very good safety profile, with a significant reduction in the risk of serious cardiovascular events compared to leuprolide. The evidence indicates that adverse events are mostly mild to moderate, supporting its tolerability.
Comparator Selection
The evaluation included appropriate comparators, primarily leuprolide and other GnRH agonists. The use of a blended comparator based on Healthcare prescribing data is appropriate, although some uncertainty exists regarding the representativeness of the data.
Patient Population and Subgroups
The HERO trial included a diverse population of patients with advanced hormone-sensitive prostate cancer, and the committee concluded that the results are generalizable to the populations included in the marketing authorization.
Care Pathway Integration
Relugolix can be integrated into existing care pathways with minimal disruption, as it is an oral treatment that does not require new infrastructure or extensive training for healthcare providers.
Resource Use and Cost Implications
The budget impact of relugolix is manageable, with the potential for cost savings due to reduced adverse events and hospitalizations associated with injectable ADTs. The overall resource use is expected to be justifiable given the treatment benefits.
Evidence Quality and Robustness
The evidence base is robust, primarily derived from the Phase 3 HERO trial, which is well-designed and provides high-quality data. The committee noted some limitations in indirect comparisons but overall found the evidence credible.
Uncertainty, Sensitivity, and Broader Impacts
While there are some uncertainties regarding the indirect treatment comparisons, the overall context supports the use of relugolix, particularly given the unmet need in advanced hormone-sensitive prostate cancer. The committee found the societal context favorable.
