Faricimab, approved in Europe for visual impairment due to macular edema secondary to retinal vein occlusion since July 2024, has failed to demonstrate an added benefit over comparator therapies ranibizumab or aflibercept in a recent assessment by the German Institute for Quality and Efficiency in Health Care (IQWiG). The assessment, part of the early benefit assessment according to the Act on the Reform of the Market for Medicinal Products (AMNOG), found that the drug manufacturer did not present suitable data to support claims of superior efficacy.
The manufacturer submitted results from the completed randomized controlled trials (RCTs) BALATON and COMINO, which compared faricimab and aflibercept. However, IQWiG determined that the treatment regimens in these studies did not align with the specifications outlined in the Summary of Product Characteristics. Specifically, patients continued to receive treatment even when their conditions had stabilized, and individualization of dosing regimens was not possible during the study phase comparing faricimab with aflibercept. This lack of individualized dosing rendered the studies unsuitable for a reliable benefit assessment.
Dosing Regimen Concerns
According to the Summary of Product Characteristics, both faricimab and aflibercept treatments should commence with administrations every four weeks, potentially requiring three or more consecutive monthly injections. Subsequently, treatment should be adjusted individually based on disease activity, following a treat-and-extend dosing regimen. Data from the BALATON and COMINO studies indicated that a significant proportion of patients stabilized after 8 to 12 weeks. However, the study design only allowed for individual adjustment of the dosing regimen in the second, non-comparative half of the study, starting from Week 24, where all patients received faricimab. Consequently, many patients continued on unchanged treatment regimens despite stable findings, and comparative data on individualized dosing regimens between faricimab and aflibercept are lacking.
EMA Recommendation Not Followed
The European Medicines Agency (EMA) had explicitly recommended to the manufacturer, as part of its consultation, that a study incorporating a treat-and-extend dosing regimen be established in both study arms. This recommendation was not followed, raising concerns about the robustness of the evidence supporting faricimab's added benefit.
Comparison with TALON Study
In contrast, the RCT TALON, which compares brolucizumab and aflibercept for neovascular (wet) age-related macular degeneration, employed a treat-and-extend regimen in both arms. This allowed for individual adjustment of treatment intervals based on disease activity, making the study suitable for the early benefit assessment of brolucizumab conducted earlier in 2024.
Next Steps
Following the publication of the dossier assessment, the G-BA will conduct a commenting procedure before making a final decision on the extent of any added benefit offered by faricimab.
