EFFICACY AND SAFETY OF FINERENONE IN PATIENTS WITH NEPHRECTOMY: A FIDELITY SUBANALYSIS

Introduction:

Finerenone, a non-steroidal mineralocorticoid receptor antagonist, significantly reduced the risk of cardiovascular and kidney outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) in FIDELITY, a prespecified pooled analysis of the phase III FIDELIO-DKD (NCT02540993) and FIGARO-DKD (NCT02545049) trials. However, the impact of finerenone on CKD progression in patients with a history of nephrectomy has not been assessed. Therefore, this subanalysis examined the efficacy and safety of finerenone in patients with CKD and T2D from FIDELITY who had undergone nephrectomy.

Methods:

Patients in FIDELITY were randomized 1:1 to finerenone or placebo treatment and were on maximum tolerated renin–angiotensin system inhibition. Identification of nephrectomy in patient medical history was based on the MedDRA Preferred Term, and corresponding procedure dates were recorded. Patients were grouped based on history of nephrectomy (yes vs no). Treatment efficacy was assessed using a mixed-model analysis of urinary albumin-to-creatinine ratio (UACR) from month 4 to 24 compared with baseline. Safety outcomes included treatment-emergent adverse events and laboratory assessments.

Results:

Of 12,990 patients included in FIDELITY, 108 patients (0.8%) had a history of nephrectomy at baseline; 101 (94%) had radical nephrectomy and 55 (50.9%) received finerenone. The median time from nephrectomy to randomization was ~15 years. At baseline, the mean estimated glomerular filtration rate was lower in patients with nephrectomy (47.7 ± 17.1 mL/min/1.73 m2) than in those without nephrectomy (57.7 ± 21.7 mL/min/1.73 m2). Other baseline characteristics were generally well-balanced between the 2 groups. Among patients with a history of nephrectomy, those receiving finerenone had a greater reduction in UACR from baseline vs placebo at 4 months (least squares [LS] mean, 0.65 vs 1.09; LS mean treatment ratio, 0.60; 95% confidence interval, 0.48–0.76; p<0.0001). This effect was maintained through year 2 (Figure 1A) and a similar trend was observed in patients without a history of nephrectomy (Figure 1B). Overall, safety outcomes were similar between the finerenone and placebo groups for patients with and without nephrectomy. Among patients with nephrectomy, treatment-emergent hyperkalemia occurred in 7.3% (n=4) of those in the finerenone group and 5.7% (n=3) of those in the placebo group; in patients without nephrectomy, the respective values were 14.1% (n=904) and 6.9% (n=445).

Conclusions:

Finerenone treatment significantly reduced albuminuria compared with placebo in patients with and without nephrectomy. These results suggest that finerenone may delay CKD progression and morbidity in patients with CKD and T2D irrespective of nephrectomy status.

I have potential conflict of interest to disclose.
JMM has nothing to disclose. MW reports that he is a scientific advisor for AstraZeneca, NovoNordisk, Mineralys, CSL Vifor, Boehringer Ingelheim, and Bayer. SDA has received research support from Abbott Vascular and Vifor Pharma, and personal fees from Abbott Vascular, Bayer, Boehringer Ingelheim, BRAHMS, Cardiac Dimensions, Impulse Dynamics, Novartis, Servier, and Vifor Pharma. GF reports lecture fees and/or that he is a committee member of trials and registries sponsored by Amgen, Bayer, Boehringer Ingelheim, Medtronic, Novartis, Servier, and Vifor Pharma. He is a senior consulting editor for JACC Heart Failure and has received research support from the European Union. PR reports personal fees from Bayer during the conduct of the study. He has received research support and personal fees from AstraZeneca, Bayer, and Novo Nordisk, and personal fees from Astellas Pharma, Abbott, Boehringer Ingelheim, Eli Lilly, Gilead, Mundipharma, Novartis, Sanofi, and Vifor Pharma; all fees are given to Steno Diabetes Center Copenhagen. STF is a full time employee of Bayer US. CA, KR, MB, and AHB are full time employees of Bayer AG. AF is an inventor on pending or issued patents (US10.183.038, US10.052.345) aimed at diagnosing or treating proteinuric kidney diseases and therefore stands to gain royalties from their future commercialization. She is Chief Scientific Officer of L&F Health LLC, holds equity interests in L&F Research, and is the inventor of assets developed by ZyVersa Therapeutics. ZyVersa has licensed worldwide rights to develop and commercialize hydroxypropyl-β-cyclodextrin for the treatment of kidney disease from L&F Research. AF is also the inventor of assets developed by River 3 Renal Corporation and holds equity in River 3 Renal Corporation. She has received research support from Pfizer and from Aurinia. Funding sources/commercial support: Commercial support from Bayer

I did not use generative AI and AI-assisted technologies in the writing process.