Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
CagriSema demonstrated a moderate benefit over current care, with significant weight loss compared to placebo in pivotal trials (REDEFINE 1 and REDEFINE 2). However, the head-to-head trial (REDEFINE 4) did not meet its non-inferiority objective against tirzepatide, indicating some uncertainty in comparative effectiveness.
Cost effectiveness
No CagriSema-specific cost-utility analysis (ICER/QALY) was identified, and the lack of economic models or cost data makes it impossible to assess cost-effectiveness, leading to a non-cost-effective classification.
Quality of life
While there were significant improvements in physical function scores reported in REDEFINE 1 and REDEFINE 2, the absence of EQ-5D utilities or comprehensive HRQoL data limits the overall assessment of quality of life impacts.
Supporting Domains
Safety and Adverse Effects
CagriSema has a very good safety profile, with most adverse events being mild to moderate, primarily gastrointestinal. Serious adverse events were reported but were not significantly higher than placebo, indicating good tolerability.
Comparator Selection
The trials included appropriate comparators, including placebo and active comparators (semaglutide and tirzepatide), allowing for a robust evaluation of CagriSema’s efficacy relative to existing treatments.
Patient Population and Subgroups
The trials enrolled a diverse population across multiple countries, with substantial representation of key demographics. However, some subgroup analyses were limited, which slightly affects generalizability.
Care Pathway Integration
CagriSema’s integration into existing care pathways appears feasible with weekly administration, but the lack of real-world data on monitoring and training requirements limits the assessment.
Resource Use and Cost Implications
No data on resource use or cost implications were available, making it impossible to assess the broader economic impact of CagriSema, leading to a classification of unsustainable budget impact.
Evidence Quality and Robustness
The evidence is based on high-quality phase 3 randomized controlled trials with clear endpoints and large sample sizes, providing a strong foundation for the evaluation of CagriSema.
Uncertainty, Sensitivity, and Broader Impacts
There are significant uncertainties regarding long-term efficacy and safety, particularly in the absence of real-world evidence and economic models, which may impact broader access and equity considerations.
