Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The evidence from the phase 3 ROSELLA trial demonstrates a clear clinical advantage with significant improvements in both progression-free survival (6.54 vs 5.52 months, HR 0.70) and overall survival (16.0 vs 11.9 months, HR 0.65) compared to nab-paclitaxel alone. This substantial evidence from a phase 3 trial supports the rating.
Cost effectiveness
The economic evidence is inconsistent and largely based on non-HTA models. The most recent phase 3-based model reported an ICER of $161,753/QALY, which is well above common thresholds, indicating questionable cost-effectiveness.
Quality of life
There is a complete absence of validated HRQoL data specific to relacorilant in the pivotal studies. No patient-reported outcomes or caregiver benefits were identified, indicating a significant gap in this domain.
Supporting Domains
Safety and Adverse Effects
The safety profile shows manageable adverse events, with a higher incidence of grade 3 or higher adverse events (74.5% vs 59.5% for nab-paclitaxel alone). However, the overall safety is acceptable with specific risks that can be monitored.
Comparator Selection
The phase 3 trial compared relacorilant plus nab-paclitaxel against nab-paclitaxel alone, which is a relevant but not comprehensive comparator. Other active regimens commonly used in practice were not included, limiting the robustness of the comparison.
Patient Population and Subgroups
The trial population is clinically relevant, with a well-defined cohort of heavily pretreated patients. However, there are concerns regarding underrepresentation of certain demographics, which affects generalizability.
Care Pathway Integration
Relacorilant can be integrated into existing pathways without the need for companion diagnostics, although monitoring for adverse effects is necessary. This makes it relatively easy to incorporate into standard oncology practice.
Resource Use and Cost Implications
The implementation burden is moderate, with increased direct medical costs due to the addition of relacorilant. However, potential reductions in downstream resource use from lower ascites may offset some costs.
Evidence Quality and Robustness
The core efficacy evidence is robust, supported by a phase 3 randomized trial with independent review. However, limitations in long-term follow-up and absence of real-world validation reduce overall confidence.
Uncertainty, Sensitivity, and Broader Impacts
There is moderate uncertainty regarding economic outcomes and access issues, particularly due to the drug’s price sensitivity and the need for prior bevacizumab treatment, which may limit patient access.
