No Added Benefit in Early Assessments
Since its approval in July 2024 for treating visual impairment caused by macular edema secondary to retinal vein occlusion, faricimab has drawn attention in the healthcare sector. However, a recent evaluation by the German Institute for Quality and Efficiency in Health Care (IQWiG) concluded that the drug lacks evidence of offering significant advantages over existing treatments such as ranibizumab or aflibercept. The manufacturer’s submitted data from two randomized controlled trials (RCTs)—BALATON and COMINO—were deemed unsuitable for demonstrating a benefit, primarily due to discrepancies between the trials’ protocols and the approved treatment guidelines.
The major issue lay in the trials’ dosing regimens, which did not align with the Summary of Product Characteristics (SmPC). According to these guidelines, both faricimab and aflibercept treatments should initially involve consecutive monthly injections, followed by a treat-and-extend approach individualized to patient needs based on disease activity. In contrast, the trials continued administering treatments even after patient conditions had stabilized, rendering the results inadequate for a meaningful benefit comparison.
Criticism of Study Design and Manufacturer Decisions
The lack of individualized treatment regimens during critical phases of the trials was a focal point of IQWiG’s critique. While the data indicated that many patients achieved stabilization of visual acuity within 8 to 12 weeks, individualized adjustments were only allowed after Week 24—well into the non-comparative phase of the trials where all patients received faricimab. This omission left no reliable data to compare farcical and aflibercept under real-world, individualized dosing conditions.
The European Medicines Agency (EMA) had explicitly recommended that the manufacturer design the trials with a treat-and-extend regimen for both study arms, reflecting clinical practices. However, the manufacturer did not follow this guidance. This decision not only weakened the study’s reliability but also set farcical apart from comparable studies like the TALON trial for brolucizumab, which successfully implemented a treat-and-extend approach for neovascular (wet) age-related macular degeneration.
The TALON study highlighted how individualized treatment intervals, tailored to disease activity, can provide actionable insights for early benefit assessments. By neglecting a similar structure, the BALATON and COMINO trials missed the opportunity to establish faricimab’s potential advantage.
Future Steps and Regulatory Decision-Making
The findings from IQWiG’s assessment form part of Germany’s early benefit evaluation process under the Act on the Reform of the Market for Medicinal Products (AMNOG). This process involves a dossier assessment, followed by a public commenting period and a final decision by the Federal Joint Committee (G-BA) on the extent of any added benefit.
While faricimab remains an approved treatment option, its failure to demonstrate superiority over existing therapies raises questions about its competitive positioning. The G-BA’s forthcoming decision will ultimately determine its perceived value within Germany’s healthcare system. For now, the manufacturer faces scrutiny for not aligning its trials with established recommendations, potentially hampering faricimab’s broader adoption and clinical appeal.
