Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The clinical trial MYR 301 demonstrated that bulevirtide significantly improved virological and biochemical responses compared to standard care at 48 weeks, with a statistically significant difference. However, the evidence is limited to this timeframe, and longer-term efficacy remains uncertain, preventing a higher rating.
Cost effectiveness
The ICER for bulevirtide is estimated at £23,083 per QALY gained, which is within NICE’s acceptable range. The committee acknowledged the uncertainties but concluded that the cost-effectiveness estimates are defensible.
Quality of life
The treatment is expected to improve quality of life by reducing viral load and associated symptoms, as indicated by clinical expert opinions. However, the evidence from the EQ-5D data was not fully validated, leading to a moderate rating.
Supporting Domains
Safety and Adverse Effects
Bulevirtide has a favorable safety profile with mostly mild to moderate adverse effects reported in the MYR 301 trial. Serious adverse events were rare, supporting a strong tolerability rating.
Comparator Selection
The treatment was compared against standard care, which is appropriate given the context of chronic hepatitis D management. The evidence supports the relevance of the comparator used in the trial.
Patient Population and Subgroups
The trial population included patients with chronic hepatitis D and compensated liver disease, which aligns with the intended use of bulevirtide. However, there are some concerns regarding the generalizability of the results to the broader population.
Care Pathway Integration
Bulevirtide can be integrated into existing treatment pathways with minor adjustments, such as training for self-administration. This indicates a good fit within current clinical practice.
Resource Use and Cost Implications
The budget impact is manageable, and the treatment is expected to provide net savings in the long term due to reduced complications from hepatitis D. This supports a favorable rating.
Evidence Quality and Robustness
The evidence is based on a Phase 3 RCT (MYR 301) with a robust design, although there are some limitations regarding the duration of follow-up and the need for additional data to confirm long-term outcomes.
Uncertainty, Sensitivity, and Broader Impacts
There are significant uncertainties regarding the long-term efficacy and safety of bulevirtide, particularly beyond the 48-week treatment period. This uncertainty could impact broader health system implications.
