Finerenon (1) – Kerendia®

• Clinical trials
  • The FIDELIO-DKD trial 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, conducted from September 2015 to February 2021.

Adults with chronic kidney disease (stages 3 and 4 with albuminuria) in conjunction with type 2 diabetes

• An additional benefit is not proven.
• mortality
  • For the endpoint of all-cause mortality, the meta-analysis of the FIDELIO-DKD and FIGARO-DKD studies shows no statistically significant difference between the treatment groups.
• morbidity
  • For the composite endpoint of renal morbidity with a decline in eGFR of ≥ 57 per cent, as well as for the individual component of a decline in eGFR of ≥ 57 per cent, the meta-analysis of the FIDELIO-DKD and FIGARO-DKD meta-analyses, a statistically significant advantage was observed in each case in favour of finerenone compared with placebo.
  • For the individual components of renal failure, sustained decline in eGFR to < 15 ml/min/1.73 m², ESRD and renal death, the meta-analysis of the FIDELIO-DKD and FIGARO-DKD studies showed no statistically significant difference between the treatment groups.
  • For the endpoint ‘confirmed progression of CKD to stage 4 or 5’, only the FIDELIO-DKD study showed a statistically significant advantage of finerenone compared with placebo. This result could not be confirmed in the meta-analysis of the FIDELIO-DKD and FIGARO-DKD studies.
  • The composite 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 (defined 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.
  • 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 – KDQOL-36 assessed using MMRM
  • For the PCS domain of the KDQOL-36, the meta-analysis of the FIDELIO-DKD and FIGARO-DKD studies shows a statistically significant advantage for finerenone compared with placebo. However, the effect does not lie outside the irrelevance range (standardised mean difference [-0.2; 0.2]). It cannot therefore be concluded that the effect is clinically relevant.
  • For the MCS domain, the burden of kidney disease, symptoms and problems associated with kidney disease, and the impact of kidney disease on daily life as measured by the KDQOL-36, 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
  • 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.
  • The pU does not provide data on the proportion of patients who experienced a treatment interruption (> 3 days) or the corresponding duration of the interruption. In the overall population of the FIDELIO-DKD study, 53.6% of patients in the intervention arm and 45.0% in the control arm discontinued treatment; in the overall population of the FIGARO-DKD study, 50.3% of patients in the intervention arm and 47.4% in the control arm interrupted their treatment.
  • Consequently, no suitable data are available for the endpoints in the ‘side effects’ category.
• Overall assessment
  • In the morbidity category, a statistically significant advantage in favour of finerenone over placebo was observed only for the endpoint ‘eGFR decline ≥ 57%’.
  • No statistically significant or clinically relevant differences were observed between the treatment arms for the endpoints cardiovascular morbidity, health status (EQ-5D VAS) and total hospitalisation.
  • In the health-related quality of life category, a statistically significant advantage of finerenone over placebo was demonstrated for the PCS domain of the KDQOL-36, a statistically significant advantage of finerenone over placebo was demonstrated in the meta-analysis of the FIDELIO-DKD and FIGARO-DKD studies; however, this advantage does not lie outside the margin of irrelevance.
  • No suitable data are available for the endpoints in the ‘side effects’ category.
  • In the overall conclusion, taking into account the uncertainties regarding the unassessable results on adverse events and the implementation of the appropriate comparator therapy, the minor advantage for the endpoint ‘eGFR decline ≥ 57 per cent’ is not sufficient to justify an additional benefit.
  • Against this background, the G-BA concludes that an additional benefit of finerenone over the appropriate comparator therapy – optimised standard therapy – is not proven.

Courtesy translation only, please refer to the German original.