Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The clinical effectiveness of garadacimab is supported by the VANGUARD trial, a Phase 3 randomized controlled trial that demonstrated an 86.5% reduction in the mean number of hereditary angioedema attacks compared to placebo. Additionally, indirect comparisons suggest that garadacimab’s effectiveness is comparable or superior to existing treatments like berotralstat and C1-INHs. However, the lack of direct head-to-head trials introduces some uncertainty.
Cost effectiveness
The cost-effectiveness estimates for garadacimab are within the range that NICE considers acceptable, particularly for patients with 2 or more attacks a month. The committee concluded that the most plausible ICER is around the middle of the range NICE considers a cost-effective use of NHS resources, although there remains some uncertainty regarding the estimates.
Quality of life
The evidence indicates that garadacimab significantly improves health-related quality of life by reducing the frequency of attacks, which is associated with decreased anxiety and improved daily functioning. The committee noted that long periods of being attack-free lead to substantial improvements in quality of life, although some aspects of HRQoL related to attack severity were not fully captured.
Supporting Domains
Safety and Adverse Effects
Garadacimab has a favorable safety profile, with adverse events primarily being mild to moderate. The committee noted that the treatment is generally well-tolerated, with serious adverse events being rare, which supports its use as a preventive treatment option.
Comparator Selection
The comparators selected for the evaluation, including berotralstat and C1-INHs, are appropriate as they represent current standard treatments for hereditary angioedema. The committee acknowledged that while indirect comparisons were necessary, they were based on robust evidence from relevant trials.
Patient Population and Subgroups
The trial population in the VANGUARD study included individuals aged 12 years and older with hereditary angioedema, which aligns with the intended patient population for garadacimab. The committee noted that while the population was generally representative, there were some concerns regarding the generalizability of results to the UK population.
Care Pathway Integration
Garadacimab can be integrated into existing care pathways with minimal disruption, as it is a self-administered treatment that does not require significant changes to current clinical practices. The committee noted that this ease of integration is a significant advantage for patients and healthcare providers.
Resource Use and Cost Implications
The resource implications of implementing garadacimab are manageable, with the potential for cost savings due to reduced attack frequency and associated healthcare costs. The committee recognized that while there is a notable cost, it is justified by the benefits provided.
Evidence Quality and Robustness
The evidence base for garadacimab is supported by a Phase 3 trial and indirect comparisons, which provide a strong foundation for decision-making. However, the committee noted some limitations in the evidence, particularly regarding the lack of direct comparisons with all relevant treatments.
Uncertainty, Sensitivity, and Broader Impacts
While there are uncertainties related to the cost-effectiveness estimates and the long-term effectiveness of garadacimab, the committee concluded that these uncertainties are manageable and do not preclude its recommendation. The treatment addresses a significant unmet need in the patient population.
