Finerenon (3) – Kerendia®

• Clinical trials
  • The FINEARTS-HF trial was conducted as a double-blind, placebo-controlled, randomised, parallel-group trial between September 2020 and June 2024.
  • In addition, the pharmaceutical manufacturer identifies the FIDELIO-DKD and FIGARO-DKD trials conducted in the therapeutic indication of kidney disease associated with type 2 diabetes mellitus.

Adults with symptomatic, chronic heart failure with preserved ejection fraction (HFpEF; LVEF ≥ 50%) or with mildly reduced ejection fraction (HFmrEF; LVEF 40 to 49%)

• An additional benefit is not proven.
• To assess the additional benefit of finerenone for the new indication for the treatment of adults with symptomatic, chronic heart failure with an LVEF ≥ 40 per cent, the pharmaceutical manufacturer has submitted the FINEARTS-HF study, on which the marketing authorisation is based.
• In the overall assessment, the results of the FINEARTS-HF study are used for the benefit assessment, taking into account the entire population.
• Overall, whilst there are uncertainties regarding the generalisability of the study results to the current German healthcare context, there is a statistically significant advantage of finerenone over the comparator arm for the endpoint ‘hospitalisation due to heart failure’.
• However, the difference in the number of events occurring between the intervention and control arms is minor at 2.1 per cent (450 versus 514 events).
• Furthermore, statistically significant disadvantages were observed for finerenone in terms of renal function for the endpoint ‘persistent decline in eGFR to < 15 ml/min/ 1.73 m²’ and, in detail, for the specific AE ‘diseases of the kidneys and urinary tract (SAE)’ and ‘hyperkalaemia (SAE)’.
• On balance, the GBA therefore concludes that, for the morbidity endpoint category as a whole, there are no relevant advantages that would justify the conclusion of an additional benefit.
• mortality
  • Overall mortality and cardiovascular death
  • No statistically significant differences were observed between the treatment arms in terms of overall mortality.
  • Similarly, no statistically significant differences were observed for the additional endpoint ‘cardiovascular death’.
• Morbidity – Hospitalisation due to heart failure
  • In patients with chronic heart failure, ‘hospitalisation due to heart failure’ generally occurs when symptoms worsen as a result of the condition.
  • There is a statistically significant advantage of finerenone compared with the comparator arm for the endpoint ‘hospitalisation due to heart failure’.
• Morbidity – total hospitalisation
  • For the endpoint ‘total hospitalisation’, defined as the time to the first occurrence of hospitalisation for any cause, no statistically significant differences were observed between the treatment arms.
• Morbidity – myocardial infarction and stroke
  • For the endpoints ‘myocardial infarction’ and ‘stroke’, there were no statistically significant differences between the treatment arms in either case.
• Morbidity – atrial fibrillation
  • For the endpoint ‘first occurrence of atrial fibrillation’, no statistically significant differences were observed between the treatment arms.
• Health-related quality of life – Kansas City Cardiomyopathy Questionnaire – Overall Summary Score (KCCQ-OSS)
  • For the clinical total score KCCQ-OSS, based on mean differences up to month 12, there is a statistically significant advantage of finerenone compared with the comparator arm.
  • As the standardised mean difference, together with the associated 95% confidence interval, does not lie entirely outside the non-significant range of –0.2 to 0.2, it cannot be concluded that the observed effect is clinically relevant.
• Side effects – Serious adverse events (SAEs)
  • No statistically significant differences were observed between the treatment groups in the overall rate of SAE.
• Overall assessment
  • For the mortality category, there is no statistically significant difference between the treatment arms for the endpoint ‘all-cause mortality’.
  • In the morbidity endpoint category, there was a statistically significant advantage for finerenone over the comparator arm for the endpoint ‘hospitalisation due to heart failure’.
  • For the endpoint ‘persistent decline in eGFR to < 15 ml/min/1.73 m²’, which was assigned to the morbidity category in accordance with the study protocol, there was a statistically significant disadvantage of finerenone compared with the comparator arm.
  • For the other endpoints in the morbidity category – ‘total hospitalisation’, ‘myocardial infarction’, ‘stroke’, ‘severe renal impairment or renal failure’, ‘decrease in eGFR of ≥ 57 per cent’, ‘initiation of dialysis or kidney transplantation’, as well as in health status, assessed using the EQ-5D VAS, no statistically significant differences were observed between the treatment arms.
  • In the health-related quality of life endpoint category, data are available for the clinical total score (KCCQ-OSS) based on mean differences up to month 12. Although this indicates a statistically significant advantage of finerenone over the comparator arm, it cannot be concluded that the observed effect is clinically relevant.
  • In the ‘side effects’ category, there were no statistically significant differences between the treatment arms for the overall rates of SAEs or for the endpoint ‘therapy discontinuations due to AEs’.
  • In detail, for the specific AEs ‘kidney and urinary tract disorders (SAE)’ and ‘hyperkalaemia (SAE)’, finerenone showed a statistically significant disadvantage compared with the comparator arm in each case.
  • These are consistent with the disadvantage observed in the ‘morbidity’ endpoint category for the renal function parameter ‘persistent decline in eGFR to < 15 ml/min/1.73 m²’.
  • Overall, whilst there are uncertainties regarding the generalisability of the study results to the current German healthcare context, there is a statistically significant advantage of finerenone over the comparator arm for the endpoint ‘hospitalisation due to heart failure’.
  • However, the difference in the number of events occurring between the intervention and control arms is minor at 2.1% (450 versus 514 events).
  • Furthermore, there is a statistically significant disadvantage to the detriment of finerenone for the endpoint ‘persistent decline in eGFR to < 15 ml/min/1.73 m²’.
  • On balance, the GBA therefore concludes that, for the endpoint category of morbidity, there are no relevant advantages overall that would justify the conclusion of an additional benefit.
  • Overall, the additional benefit of finerenone in adults with symptomatic chronic heart failure with an LVEF ≥ 40 % compared with the appropriate comparator therapy is not proven.

Courtesy translation only, please refer to the German original.