Bayer Ag · XETR:BAYN
Bayer — Technical Presentation (2025)
52 slides from Bayer's technical presentation, 2025
Slide 1: Combination Effect of Finerenone and Empagliflozin in CKD and T2D (CONFIDENCE)—Baseline Characteristics
COMBINATION EFFECT OF FINERENONE AND EMPAGLIFLOZIN IN PARTICIPANTS WITH CHRONIC KIDNEY DISEASE AND TYPE 2 DIABETES USING A UACR ENDPOINT STUDY (CONFIDENCE)—BASELINE CHARACTERISTICS Rajiv Agarwal, MD, MS Professor Emeritus, Indiana University USA
Slide 2: Coauthors
COAUTHORS Jennifer B. Green Julio Rosenstock Hiddo J. L. Heerspink Peter Rossing Johannes F. E. Mann Muthiah Vaduganathan Janet B. McGill Meike Brinker Amy K. Mottl Robert Edfors Na Li Markus F. Scheerer Charlie Scott Masaomi Nangaku
Slide 3: Disclosures for Rajiv Agarwal
DISCLOSURES FOR RAJIV AGARWAL This work was supported by Bayer AG, who funded the CONFIDENCE study Received personal fees and nonfinancial support from Akebia Therapeutics, Alnylam, Bayer Healthcare Pharmaceuticals, Boehringer Ingelheim, Intercept, and Novartis Member of data safety monitoring
Slide 4: All Author Disclosures
ALL AUTHOR DISCLOSURES JBG has received funds for research, paid to her institution, from Bluedrop, Boehringer Ingelheim, Eli Lilly, Merck, and Roche; and is a consultant for Anji, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Mineralys, Novo Nordisk, Pfizer, Valo, and Vertex. HJLH has receiv
Slide 5: Introduction
INTRODUCTION Despite available interventions, people with CKD associated with T2D remain at risk of kidney failure and cardiovascular complications ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; CKD, chronic kidney disease; MRA, mineralocorticoid receptor antagonis
Slide 6: Introduction
INTRODUCTION Despite available interventions, people with CKD associated with T2D remain at risk of kidney failure and cardiovascular complications Finerenone, a potent and selective nonsteroidal MRA, and SGLT2 inhibitors have each been shown to reduce both kidney and cardiovascular risks in people
Slide 7: Introduction
INTRODUCTION Despite available interventions, people with CKD associated with T2D remain at risk of kidney failure and cardiovascular complications Finerenone, a potent and selective nonsteroidal MRA, and SGLT2 inhibitors have each been shown to reduce both kidney and cardiovascular risks in people
Slide 8: Introduction
INTRODUCTION Despite available interventions, people with CKD associated with T2D remain at risk of kidney failure and cardiovascular complications Finerenone, a potent and selective nonsteroidal MRA, and SGLT2 inhibitors have each been shown to reduce both kidney and cardiovascular risks in people
Slide 9: Rationale for Use of Finerenone + SGLT2 Inhibitor Combination
RATIONALE FOR USE OF FINERENONE + SGLT2 INHIBITOR COMBINATION Finerenone and SGLT2 inhibitors1: Shared and distinct physiological effects Finerenone1: Oxidative stress, inflammation, fibrosis, improves endothelial function SGLT2 inhibitor1: Kidney hemodynamic effect ➔ glucosuria and natriuresi
Slide 10: Rationale for Use of Finerenone + SGLT2 Inhibitor Combination
RATIONALE FOR USE OF FINERENONE + SGLT2 INHIBITOR COMBINATION Finerenone and SGLT2 inhibitors1: Shared and distinct physiological effects Finerenone1: Oxidative stress, inflammation, fibrosis, improves endothelial function SGLT2 inhibitor1: Kidney hemodynamic effect ➔ glucosuria and natriuresi
Slide 11: Rationale for Use of Finerenone + SGLT2 Inhibitor Combination
RATIONALE FOR USE OF FINERENONE + SGLT2 INHIBITOR COMBINATION Finerenone and SGLT2 inhibitors1: Shared and distinct physiological effects Finerenone1: Oxidative stress, inflammation, fibrosis, improves endothelial function Post hoc analyses2: SGLT2 inhibitor1: Beneficial effects of Kidney hemo
Slide 12: Rationale for Use of Finerenone + SGLT2 Inhibitor Combination
RATIONALE FOR USE OF FINERENONE + SGLT2 INHIBITOR COMBINATION Secondary analyses of FIDELITY Using population However, no trial has yet (a pooled analysis of the pharmacokinetics and evaluated the safety and efficacy FIGARO-DKD and FIDELIO-DKD pharmacodynamics in a pooled of simultaneously initiatin
Slide 13: Rationale for Use of Finerenone + SGLT2 Inhibitor Combination
RATIONALE FOR USE OF FINERENONE + SGLT2 INHIBITOR COMBINATION Secondary analyses of FIDELITY Using population However, no trial has yet (a pooled analysis of the pharmacokinetics and evaluated the safety and efficacy FIGARO-DKD and FIDELIO-DKD pharmacodynamics in FIDELITY, of simultaneously initiati
Slide 14: Rationale for Use of Finerenone + SGLT2 Inhibitor Combination
RATIONALE FOR USE OF FINERENONE + SGLT2 INHIBITOR COMBINATION Secondary analyses of FIDELITY Using population However, no trial has yet (a pooled analysis of the pharmacokinetics and evaluated the safety and efficacy FIGARO-DKD and FIDELIO-DKD pharmacodynamics in FIDELITY, of simultaneously initiati
Slide 15: CONFIDENCE Study Design: Randomized, Double-Blind, Phase 2 Study
CONFIDENCE STUDY DESIGN: A RANDOMIZED, CONTROLLED, DOUBLE-BLIND, DOUBLE-DUMMY, INTERNATIONAL, MULTICENTER, THREE-ARMED, PARALLEL- GROUP, PHASE 2 STUDY 15
Slide 16: CONFIDENCE Study Design
CONFIDENCE STUDY DESIGN Randomized participants were stratified by eGFR and UACR at screening Stratification: UACR, mg/g Screening (≤850, >850) R Stratification: eGFR, mL/min/1.73 m2 (<60, ≥60) †Participants with an eGFR of 40–90 mL/min/1.73 m2 were recruited (Part A) prior to recruiting participant
Slide 17: CONFIDENCE Study Design
CONFIDENCE STUDY DESIGN Participants were randomized in a 1:1:1 ratio to one of three parallel groups Stratification: Finerenone (10 or 20 mg once daily) and empagliflozin (10 mg once daily) UACR, mg/g Screening (≤850, >850) R Finerenone (10 or 20 mg once daily) and placebo 1:1:1 Stratification: eGF
Slide 18: CONFIDENCE Study Design
CONFIDENCE STUDY DESIGN CONFIDENCE comprised two consecutive parts. In Part A, participants with an eGFR of 40–90 mL/min/1.73 m2 were enrolled and underwent ABPM for 24 hours after administration of their first study drug dose on Day 1. A decision to extend enrolment to participants with an eGFR as
Slide 19: CONFIDENCE Study Design
CONFIDENCE STUDY DESIGN The treatment period spans from Day 1 to Day 180, with study visits on Days 1, 14, 30, 90, and 180 Start of treatment Treatment period End of treatment Stratification: Finerenone (10 or 20 mg once daily) and empagliflozin (10 mg once daily) UACR, mg/g Screening (≤850, >850) R
Slide 20: CONFIDENCE Study Design
CONFIDENCE STUDY DESIGN A follow-up/end-of-study visit is scheduled 30 days after the last dose of study drug Start of treatment Treatment period End of treatment End of study Stratification: Finerenone (10 or 20 mg once daily) and empagliflozin (10 mg once daily) UACR, mg/g Follow-up Screening (≤85
Slide 21: Primary Endpoint: Relative Change from Baseline in UACR
PRIMARY ENDPOINT: RELATIVE CHANGE FROM BASELINE IN UACR AT 180 DAYS Start of treatment Treatment period End of treatment End of study Stratification: Finerenone (10 or 20 mg once daily) and empagliflozin (10 mg once daily) UACR, mg/g Screening (≤850, >850) versus R Finerenone (10 or 20 mg once daily
Slide 22: Primary Endpoint: Relative Change from Baseline in UACR
PRIMARY ENDPOINT: RELATIVE CHANGE FROM BASELINE IN UACR AT 180 DAYS Start of treatment Treatment period End of treatment End of study Stratification: Finerenone (10 or 20 mg once daily) and empagliflozin (10 mg once daily) UACR, mg/g Screening (≤850, >850) versus or R versus Finerenone (10 or 20 mg
Slide 23: Secondary UACR Endpoints
SECONDARY UACR ENDPOINTS Start of treatment Treatment period End of treatment versus versus Finerenone (10 or 20 mg once daily) and empagliflozin (10 mg once daily) or Secondary endpoints: Combined treatment Finerenone (10 or 20 mg once daily) and placebo versus either drug alone Empagliflozin (10 m
Slide 24: Secondary UACR Endpoints
SECONDARY UACR ENDPOINTS Start of treatment Treatment period End of treatment End of study versus versus Finerenone (10 or 20 mg once daily) and empagliflozin (10 mg once daily) or Secondary endpoints: Combined treatment Finerenone (10 or 20 mg once daily) and placebo versus either drug alone Empagl
Slide 25: Secondary UACR Endpoints
SECONDARY UACR ENDPOINTS Start of treatment Treatment period End of treatment End of study versus versus Finerenone (10 or 20 mg once daily) and empagliflozin (10 mg once daily) or Secondary endpoints: Combined treatment Finerenone (10 or 20 mg once daily) and placebo versus either drug alone Empagl
Slide 26: eGFR Safety Endpoints
eGFR SAFETY ENDPOINTS Start of treatment Treatment period End of treatment End of study Finerenone (10 or 20 mg once daily) and empagliflozin (10 mg once daily) Finerenone (10 or 20 mg once daily) and placebo Empagliflozin (10 mg once daily) and placebo Days 1 30 (± 4) 180 (± 5) 210 (± 5) Initial an
Slide 27: eGFR Safety Endpoints
eGFR SAFETY ENDPOINTS Start of treatment Treatment period End of treatment End of study Finerenone (10 or 20 mg once daily) and empagliflozin (10 mg once daily) Finerenone (10 or 20 mg once daily) and placebo Empagliflozin (10 mg once daily) and placebo Days 1 30 (± 4) 180 (± 5) 210 (± 5) Initial an
Slide 28: eGFR Safety Endpoints
eGFR SAFETY ENDPOINTS Start of treatment Treatment period End of treatment End of study Finerenone (10 or 20 mg once daily) and empagliflozin (10 mg once daily) Finerenone (10 or 20 mg once daily) and placebo Empagliflozin (10 mg once daily) and placebo Days 1 30 (± 4) 180 (± 5) 210 (± 5) Initial an
Slide 29: Other Safety Endpoints
OTHER SAFETY ENDPOINTS AKI; TEAEs (hyperkalemia, GMIs, symptomatic hypotension) Start of treatment Treatment period End of treatment End of study Finerenone (10 or 20 mg once daily) and empagliflozin (10 mg once daily) Finerenone (10 or 20 mg once daily) and placebo Empagliflozin (10 mg once daily)
Slide 30: Comparison of CONFIDENCE Inclusion Criteria with Other Kidney Outcome Trials
COMPARISON OF CONFIDENCE INCLUSION CRITERIA WITH OTHER KIDNEY OUTCOME TRIALS OF SGLT2 INHIBITORS AND FINERENONE 30
Slide 31: Inclusion Criteria: Comparison with SGLT2 Inhibitor Studies
INCLUSION CRITERIA: COMPARISON WITH SGLT2 INHIBITOR STUDIES CREDENCE3 DAPA-CKD4 EMPA-KIDNEY5 Criteria CONFIDENCE1,2 (Canagliflozin) (Dapagliflozin) (Empagliflozin) eGFR ≥20 to <45 (irrespective eGFR (mL/min/1.73 m2) eGFR 30 to 90 with a eGFR 30 to <90 with a eGFR 25 to 75 with a of level of albuminu
Slide 32: Inclusion Criteria: Comparison with Finerenone Studies
INCLUSION CRITERIA: COMPARISON WITH FINERENONE STUDIES Criteria CONFIDENCE1,2 FIDELIO-DKD3 FIGARO-DKD4 eGFR 25 to <60 with a eGFR 25 to 90 with a UACR of 30 to <300 UACR of 30 to <300 eGFR (mL/min/1.73 m2) eGFR 30 to 90 with a or or and/or UACR (mg/g) UACR ≥100 to <5000 eGFR 25 to <75 with a eGFR ≥6
Slide 33: Participant Disposition and Baseline Demographics in CONFIDENCE
PARTICIPANT DISPOSITION AND BASELINE DEMOGRAPHICS IN CONFIDENCE 33
Slide 34: Participant Disposition
PARTICIPANT DISPOSITION Screened N = 1664 Not included, n = 846 • Screen failure, n = 805 – Did not meet clinical diagnosis of CKD and other specified criteria, n = 314 – Met exclusion criteria K+ of >4.8 mmol/L, n = 289 – With T2D but did not meet HbA1c criterion of <11% at screening, n = 29 Random
Slide 35: Participant Disposition
PARTICIPANT DISPOSITION Screened N = 1664 Not included, n = 846 • Screen failure, n = 805 – Did not meet clinical diagnosis of CKD and other specified criteria, n = 314 – Met exclusion criteria K+ of >4.8 mmol/L, n = 289 – With T2D but did not meet HbA1c criterion of <11% at screening, n = 29 Random
Slide 36: Baseline Demographics
BASELINE DEMOGRAPHICS Total Total Characteristic (N = 801)† Characteristic (N = 801)† Age, mean years 66.5 Smoking history, % Female, % 25 Current smoker 15 Race, %‡ BMI, mean kg/m2 29 Asian 46 Body weight, mean kg 82 Asian Indian 17 SBP, mean mmHg 135 White 44 DBP, mean mmHg 77 Black/African Americ
Slide 37: Baseline Demographics by UACR Subgroup
BASELINE DEMOGRAPHICS BY UACR SUBGROUP UACR subgroup ≤850 mg/g >850 mg/g Characteristic (n = 520) (n = 281) Age, mean years 68 64 Race, % Asian 41 56 Asian Indian 14 22 White 48 37 Black/African American 10 6 Other <1 1 Region, % Asia 40 55 North America 30 24 Europe 30 21 HbA1c, % 7.2 7.5 HbA1c, gl
Slide 38: Comparison of CONFIDENCE Baseline Characteristics with Other Kidney Outcome Trials
COMPARISON OF CONFIDENCE BASELINE CHARACTERISTICS WITH OTHER KIDNEY OUTCOME TRIALS OF SGLT2 INHIBITORS AND FINERENONE SGLT2, sodium-glucose co-transporter-2. 38
Slide 39: Baseline Demographics and Clinical Characteristics by Study
BASELINE DEMOGRAPHICS AND CLINICAL CHARACTERISTICS IN PARTICIPANTS WITH CKD AND T2D BY STUDY CONFIDENCE Characteristic (N = 801) Age, mean years 67 Women, % 25 Current smoker, % 15 BMI, mean kg/m2 29 Body weight, mean kg 82 SBP, mean mmHg 135 DBP, mean mmHg 77 HbA1c, % 7.3 BMI, body mass index; CKD,
Slide 40: Baseline Characteristics: Comparison with SGLT2 Inhibitor Studies
BASELINE DEMOGRAPHICS AND CLINICAL CHARACTERISTICS: COMPARISON WITH SGLT2 INHIBITOR STUDIES CREDENCE1 DAPA-CKD2 EMPA-KIDNEY3 CONFIDENCE (Canagliflozin) (Dapagliflozin) (Empagliflozin) Characteristic (N = 801) (N = 4401) (N = 2906)† (N = 3039)† Age, mean years 67 63 64 69 Women, % 25 34 33 33 Current
Slide 41: Baseline Characteristics: Comparison with Finerenone Studies
BASELINE DEMOGRAPHICS AND CLINICAL CHARACTERISTICS: COMPARISON WITH FINERENONE STUDIES CONFIDENCE FIDELIO-DKD1 FIGARO-DKD2 Characteristic (N = 801) (N = 5674) (N = 7352) Age, mean years 67 66 64 Women, % 25 30 31 Current smoker, % 15 14 18 BMI, mean kg/m2 29 31 31 Body weight, mean kg 82 87 89 SBP,
Slide 42: Kidney Disease Characteristics in CONFIDENCE
KIDNEY DISEASE CHARACTERISTICS IN CONFIDENCE Mean eGFR†: 54 mL/min/1.73 m2 Median UACR§: 583 mg/g Distribution of eGFR categories Distribution of albuminuria categories >75 60 to 75 45 to <60 30 to <45 <30 <30 30 to 300 >300 to 1000 >1000 3% <1% 13% 28% 26% 33% 22% 29% 46% N = 801‡ N = 801‡ †Calcula
Slide 43: eGFR in Participants with CKD and T2D by Study
eGFR IN PARTICIPANTS WITH CKD AND T2D BY STUDY FIDELIO-DKD2 CONFIDENCE FIGARO-DKD5 44 54 68 eGFR, mean mL/min/1.73 m2 30 40 50 60 70 EMPA-KIDNEY1† CREDENCE4 36 56 DAPA-CKD3† 44 †Data are shown for participants with T2D only. CKD, chronic kidney disease; DKD, diabetic kidney disease; eGFR, estimated
Slide 44: UACR in Participants with CKD and T2D by Study
UACR IN PARTICIPANTS WITH CKD AND T2D BY STUDY FIGARO-DKD1 CONFIDENCE FIDELIO-DKD3 308 583 852 UACR, median mg/g 0 400 800 1200 EMPA-KIDNEY2† CREDENCE4 348 927 DAPA-CKD5† 1017 †Data are shown for participants with T2D only. CKD, chronic kidney disease; DKD, diabetic kidney disease; T2D, type 2 diabe
Slide 45: Medical History of CV and Microvascular Disease
MEDICAL HISTORY OF CV AND MICROVASCULAR DISEASE Total Characteristic (N = 801)† Medical history, %‡ Hypertension 88 ASCVD 28 Coronary artery disease 17 Myocardial infarction 5 Stroke 8 Peripheral arterial disease 7 Diabetic retinopathy 16 Atrial fibrillation 6 Heart failure 4 †There were 17 randomiz
Slide 46: Concomitant Medications and Antihyperglycemic Agents
CONCOMITANT MEDICATIONS AND ANTIHYPERGLYCEMIC AGENTS Total Total Characteristic (N = 801)† Characteristic (N = 801)† Concomitant medications, % Antihyperglycemic agents, % ACEi/ARB‡ 98 Insulin 39 Calcium channel blockers 61 GLP-1 RAs 23 Statins 39 Antiplatelet agents 40 Oral hypoglycemic agents Beta
Slide 47: Medical History and Concomitant Medications: Comparison with Other Studies
MEDICAL HISTORY AND CONCOMITANT MEDICATIONS: COMPARISON WITH OTHER STUDIES CONFIDENCE1 Characteristic (N = 801) Medical history, % ASCVD or CVD 28† Heart failure 4 Diabetic retinopathy 16 Concomitant medications, % ACEis/ARBs 98 GLP-1 RAs 23 Insulin and analogues 39 DPP-4 inhibitors 31 Metformin 60
Slide 48: Medical History and Concomitant Medications: Comparison with Other Studies
MEDICAL HISTORY AND CONCOMITANT MEDICATIONS: COMPARISON WITH OTHER STUDIES CONFIDENCE1 CREDENCE2 DAPA-CKD3 EMPA-KIDNEY4 FIDELITY5 Characteristic (N = 801) (N = 4401) (N = 2906)‡ (N = 3039)‡ (N = 13,026) Medical history, % ASCVD or CVD 28† 50 44 36 46 Heart failure 4 15 12 14 8 Diabetic retinopathy 1
Slide 49: CONFIDENCE Study: Conclusions
CONFIDENCE STUDY: CONCLUSIONS The high rates of morbidity and mortality associated with CKD in T2D highlight the unmet need for additional effective treatments for slowing CKD progression. People with both CKD and T2D are at high risk of adverse clinical outcomes because of the additive, detrimental
Slide 50: CONFIDENCE Study: Conclusions
CONFIDENCE STUDY: CONCLUSIONS The high rates of morbidity CONFIDENCE, the first and mortality associated randomized trial to examine with CKD in T2D highlight combination therapy the unmet need for comprising finerenone and additional effective an SGLT2 inhibitor in people treatments for slowing CKD
Slide 51: CONFIDENCE Study: Conclusions
CONFIDENCE STUDY: CONCLUSIONS The high rates of morbidity CONFIDENCE, the first Full details on the baseline and mortality associated randomized trial to examine characteristics of the with CKD in T2D highlight combination therapy CONFIDENCE study are the unmet need for comprising finerenone and pub
Slide 52: Thank You to Our Investigators, Staff, and Study Participants
THANK YOU TO OUR INVESTIGATORS, STAFF, AND STUDY PARTICIPANTS Author affiliations: RA – Division of Nephrology, Richard L. Roudebush VA Medical Center Indiana University School of Medicine, Indianapolis, Indiana, USA; JBG – Division of Endocrinology, Department of Medicine and Duke Clinical Research