Finerenon (2) – Kerendia®

• Clinical trials
  • The FIDELIO-DKD study was a placebo-controlled, double-blind, randomised, parallel-group trial of finerenone, conducted from September 2015 to April 2020.
  • The FIGARO-DKD trial was a placebo-controlled, double-blind, randomised, parallel-group trial of finerenone, which was conducted from September 2015 to February 2021.

Adults with chronic kidney disease (stages 1 and 2 with albuminuria) in conjunction with type 2 diabetes

• Taking into account the uncertainties mentioned, and based on an overall assessment of the positive effects and the results that could not be evaluated regarding adverse events, the G-BA identifies a hint of a non-quantifiable additional benefit.
• Overall, the FIDELIO-DKD and FIGARO-DKD studies exhibit uncertainties that limit the conclusiveness of the results.
• Against the background of these uncertainties, the certainty of the findings is therefore classified in the ‘hint’ category.
• mortality
  • For the endpoint of all-cause mortality, the meta-analysis of the FIDELIO-DKD and FIGARO-DKD studies shows a statistically significant advantage of finerenone compared with placebo.
• Morbidity – Renal failure
  • For the endpoint of renal failure, the meta-analysis of the FIDELIO-DKD and FIGARO-DKD studies shows a statistically significant advantage of finerenone compared with placebo.
  • The composite endpoint of renal failure comprises the components ESRD (end-stage renal disease, defined as the need for chronic dialysis treatment for > 30 days, unless it is apparent that dialysis treatment can be discontinued after 90 days, or a kidney transplant) and a sustained decline in eGFR to < 15 ml/min/1.73 m².
• Morbidity – Confirmed progression of CKD to stage 4 or 5
  • For the endpoint ‘confirmed progression of CKD to stage 4 or 5’, the meta-analysis of the FIDELIO-DKD and FIGARO-DKD studies shows a statistically significant advantage of finerenone compared with placebo.
  • Confirmed progression of CKD to stage 4 or 5 is clinically relevant.
• Morbidity – Composite endpoint for renal morbidity
  • The combined endpoint for renal morbidity in the studies comprises the individual components of renal failure, a decrease in eGFR of ≥ 57 per cent, and renal-related death.
  • Given the high mean baseline eGFR values (approx. 80 ml/min/1.73 m²) of the patients, it cannot be assumed in the present situation that the component ‘decrease in eGFR ≥ 57%’ is sufficiently clinically relevant.
• Morbidity – Cardiovascular morbidity (composite endpoint) and severe cardiovascular events (operationalised as cardiovascular hospitalisation)
  • The combined endpoint for cardiovascular morbidity in the studies comprises the individual components of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and severe heart failure events (operationalised as hospitalisation due to heart failure).
  • However, the analyses do not include hospitalisations for other cardiovascular reasons (e.g. hospitalisation due to atrial fibrillation, unstable angina pectoris or arrhythmias), which, for example, occurred more than twice as frequently as hospitalisations for heart failure in the FIGARO-DKD study.
  • The composite endpoint for cardiovascular morbidity therefore covers only a portion of the relevant cardiovascular events.
• Morbidity – total hospitalisation
  • For the endpoint of total hospitalisation, the meta-analysis of the FIDELIO-DKD and FIGARO-DKD studies shows no statistically significant difference between the treatment groups.
• Health-related quality of life – health status (EQ-5D VAS) assessed using MMRM
  • For the health status endpoint assessed using the EQ-5D VAS, the meta-analysis of the FIDELIO-DKD and FIGARO-DKD studies shows no statistically significant difference between the treatment groups.
• Health-related quality of life – KDQOL-36 assessed using MMRM (PCS, MCS, burden of kidney disease, symptoms and problems associated with kidney disease, and impact of kidney disease on daily life)
  • For the five domains of the KDQOL-36 – PCS, MCS, burden of kidney disease, symptoms and problems associated with kidney disease, and the impact of kidney disease on daily life, the meta-analysis of the FIDELIO-DKD and FIGARO-DKD studies revealed no statistically significant difference between the treatment groups in any of these domains.
• Side effects
  • No suitable data are available for the endpoints in the ‘side effects’ category.
  • Adverse events (AEs) were recorded in the FIDELIO-DKD and FIGARO-DKD studies throughout the entire observation period, regardless of whether patients were still receiving treatment with the study medication.
  • However, the presented analyses of AEs, SUEs and AEs leading to discontinuation only include events that occurred during treatment with the study medication and up to 3 days after a treatment interruption or therapy discontinuation.
• Overall assessment
  • An overall review of the results reveals positive effects on all-cause mortality as well as on the endpoints ‘renal failure’ and ‘confirmed progression of CKD to stage 4 or 5’.
  • However, due to the unevaluable results regarding adverse events, it is not possible to conclusively weigh up the advantages demonstrated in the study against potential harms; consequently, the additional benefit for adults with chronic kidney disease (stages 1 and 2 with albuminuria) in conjunction with type 2 diabetes cannot be quantified in terms of its extent.

Courtesy translation only, please refer to the German original.