fp179 baseline characteristics of the “cardinal” trial...conclusion baseline characteristics of...

CONCLUSION

Baseline Characteristics of the “CARDINAL” Trial: A Phase 3 Study of the Efficacy and Safety of Bardoxolone Methyl in Patients with Alport Syndrome

Bertrand Knebelmann, MD; Gerald B. Appel, MD; Geoffrey A. Block, MD; Melanie P. Chin, PhD; Angie Goldsberry, MS; Lesley A. Inker, MD;

Clifford E. Kashtan, MD; Colin J. Meyer, MD; Kandai Nozu, MD; Pablo E. Pergola, MD, PhD; Anjay Rastogi, MD, PhD; Michelle N. Rheault, MD;

Arnold L. Silva, MD, PhD; Stuart M. Sprague, DO; Bradley Warady, MD; Oliver Gross, MD

Presented at ERA-EDTA, June 14, 2019; Budapest, Hungary

CAUSE, PATHOGENESIS, AND CLASSIFICATION

• Alport syndrome (AS) is the second most common hereditary form of CKD and is caused by

mutations in genes that encode type IV collagen

— Type IV collagen comprises about 50% of the glomerular basement membrane (GBM)2

— Mutations in the COL4 genes encoding type IV collagen α3, α4, or α5 lead to a

dysfunctional GBM and AS2

— Defective GBM leads to proteinuria, inflammation, interstitial fibrosis, tubular atrophy,

glomerular sclerosis, and progressive loss of kidney function

• Inflammation, fibrosis and mitochondrial dysfunction contribute to kidney function decline in

patients withAS3-5

• New AS classification system includes all individuals with COL4A 3/4/5 mutations6

GAB, MPC, AG, and CJM are employees of Reata Pharmaceuticals.

BK, PEP, SMS, and BW are consultants to Reata Pharmaceuticals.

GBA, LAI, CEK, AR, MNR, ALS, and SMS receive research funding from

Reata Pharmaceuticals.

KN and OG have nothing to disclose.

• CARDINAL is the first randomized, placebo-controlled trial testing the long-term efficacy and safety of Bard in patients with AS

• Baseline characteristics are similar in between patients enrolled in Phase 2 and Phase 3 parts of CARDINAL

• The CARDINAL population is representative of the broader AS population and includes patients with a wide range of disease

severity who were receiving standard of care

1. NORD website: https://rarediseases.org/rare-diseases/alport-

syndrome/

2. Suh and Miner, Nat Rev Nephrol. 2013, 9(8):470-7

3. Gomez et al. J Clin Invest. 2015, 125(1):141-56

4. Jedlicka et al. Hum Pathol. 2010, 41(4):582-93

5. Kashtan et al. J Am Soc Nephrol. 1998, 9(9):1736-50

6. Kashtan et al. Kidney Int. 2018, 93(5):1045-51

7. Rheault et al. Nephrol Dial Transp. 2016,31(1):i126 Abstract

8. Jais et al. J Am Soc Nephrol. 2000, 11(4):649-57

9. Ruiz et al. Kidney Int. 2013, 83:1029-1041

10. Aminzadeh et al. Redox Biol. 2013,1:527-31

11. Ding et al. Kidney Int. 2013, 83(5):845-854

12. Huang et al. J Med Chem. 2017, 60(21):8847-8857

13. Zoja et al. J Am Soc Nephrol. 2010, 21:275A Abstract

14. Wu et al. Arthritis Rheumtol. 2014, 66(11):3129-39

15. Aminzadeh et al. Redox Biol. 2014, 44(6):570-578

16. Hisamichi et al. Hypertens Res. 2018, 41(1):8-17

17. Nangaku et al. J Am Soc Nephrol. 2017, 28:B1 Abstract

18. De Zeeuw et al. N Engl J Med, 2013, 369: 2492-2503

19. Pergola et al. N Engl J Med. 2011, 365(4):327-36

20. Chin et al. Am J Nephrol. 2018, 47:40-47

21. Meyer et al. Nephrol Dial Transp. 2018, 3(1):iii480 Abstract

22. Block et al. J Am Soc Nephrol. 2018, 29:482 Abstract

23. Silva et al. J Am Soc Nephrol. 2018, 29:772 Abstract


25. Pergola et al. J Am Soc Nephrol. 2018, 29:482 Abstract

26. Pergola et al. Am J Nephrol. 2011, 33(5):469-476

27. Data on file; RTA 402-C-0801 (NCT00664027)

CARDINAL PHASE 2 RESULTS

ALPORT SYNDROME

DISCLOSURES

REFERENCES

B

CARDINAL STUDY (NCT03019185)

• Multicenter, multinational Phase 2/3 study

• Patients 12 to 70 years of age with genetic or histologic confirmation of Alport syndrome

• Baseline eGFR between 30-90 mL/min/1.73 m2 and urinary ACR ≤ 3500 mg/g

• Required to be on stable doses of ACEi/ ARB unless contraindicated

• History of cardiovascular disease or BNP > 200 pg/mL at baseline are excluded

• Dose-titration to goal Bard dose of 20 or 30 mg given orally, once daily

PHASE 2 COHORT

• Open-label cohort enrolled a total of 30 patients

• Primary endpoint: change from baseline in eGFR at Week 12

• Following analysis at 12 weeks, patients are followed on treatment for 2 years

PHASE 3 COHORT

• Enrolled 157 patients with 2 years of total treatment duration

• Placebo-controlled, double-blind, 1:1 randomization

• Primary endpoint: change from baseline in eGFR at Week 48

• Key secondary endpoint: change from baseline in eGFR at Week 52 following a 4-week drug

withdrawal period (retained benefit)

CARDINAL STUDY DESIGN

• Bard treatment increased mean eGFR +10.4 mL/min/1.73 m2 (p<0.0001) through Week 48,

which represents recovery of approximately two years of loss20

• Significant retained benefit of 4.1 mL/min/1.73 m2 four weeks after Bard withdrawal

• UACR not significantly different from baseline at Weeks 48 or 52

• Bard was generally well-tolerated, with the most commonly reported AE being muscle spasms,

which are not associated with markers of muscle toxicity such as elevations in creatine kinase

• Blood pressure stable and within normal limits during treatment

• No evidence of overt fluid retention

CARDINAL PHASE 3 SCHEMA

FP179

BARDOXOLONE METHYL

• Bardoxolone methyl (Bard) is an investigational small-molecule drug that, by activation of Nrf2,

promotes resolution of inflammation, reduction of oxidative stress, and improved mitochondrial

function9

• Bard increases GFR acutely by reducing inflammatory signaling and restoring Kf in animal

models10,11

• Bard increases GFR chronically by reducing remodeling and fibrosis in animal models of

hyperfiltration, hypertension, diabetes, lupus, and protein overload12-16

• In 11 clinical trials, Bard increased measured or estimated GFR (eGFR) in patients with diverse

etiologies of CKD across a broad range of kidney function17-25

• No major safety signals within trials after enrolling over 1,500 patients since 2012

Urinary Albumin Not Significantly

Changed at Week 48 or Week 52

Bard Increased eGFR in Patients That

Historically Declined ~4.2 mL/min/1.73 m2

Bardoxolone methyl is an investigational drug. Safety and efficacy have not been established by any agency.

CARDINAL PHASE 3 BASELINE CHARACTERISTICS

New Classification System for COL4A3/4/5 Disorders

InheritanceAffected

gene(s)Genetic state

Estimated

Risk of ESKD

X-linked COL4A5

Hemizygous

(male subjects)100%

Heterozygous

(female subjects)Up to 25%

AutosomalCOL4A3 or

COL4A4

Recessive (homozygous or

compound heterozygous)100%

Dominant 20% or more

Digenic

COL4A3,

COL4A4,

and COL4A5

COL4A3 and COL4A4

mutations in transUp to 100%

COL4A3 and COL4A4

mutations in cisUp to 20%

Mutations in COL4A5 and in

COL4A3 or COL4A4Up to 100%

DISEASE PROGRESSION, TREATMENT, AND PREVALENCE

• Average decline in kidney function is estimated to be ~4 mL/min/1.73 m2 /year7

• Median age at onset of End Stage Kidney Disease (ESKD) for males with X-linked inheritance is

25 years8

• Standard of care includes RAASi, but no AS-specific approved therapies are available

• The National Organization for Rare Disorders (NORD) estimates that approximately 30,000 –

60,000 people in the US are affected1

• Patients enrolled have a broad range of eGFR and disease severity

• Patients enrolled are representative of the AS population, as defined by new classification system

Study Patient PopulationeGFR Range

(mL/min/1.73 m2)N ∆eGFR (mL/min1.73 m2)

CARDINAL Ph2 Alport syndrome 30 – 90 30 13.4 (p<0.001)1

PHOENIX ADPKD 30 – 90 31 9.3 (p<0.001)1

PHOENIX IgAN 30 – 90 26 8.0 (p<0.001)1

PHOENIX T1D CKD 30 – 90 28 5.5 (p=0.02)1

PHOENIX FSGS 30 – 90 18 7.8 (p=0.003)1

TSUBAKI T2D CKD 15 – 59 124 6.6 (p=0.008 vs PBO)2

BEACON T2D CKD 15 – 29 2185 6.4 (p<0.001 vs PBO)2

BEAM T2D CKD 20 – 45 227 8.6 (p<0.001 vs PBO)2

402-C-0902 T2D CKD 15 – 45 131 6.5 (p<0.001)1

Selected trials listed; 1 Change in eGFR vs. baseline; 2 Change in eGFR vs. placebo

0

5

10

15

20

-3 -2 -1 0 1

Me

an

S

E e

GF

R D

iffe

ren

ce

fro

m

CA

RD

INA

L I

nit

iati

on

(ml/

min

)

Years Prior to Study EntryCARDINAL

Initiation

-4.2 ml/min per year (n=22)

CARDINAL Historical Average eGFR Decline Bard

Week 48 ΔeGFR

+10.4 ml/min

n=25, p<0.0001

ParameterPhase 2 Phase 3

All

(N=30)

All

(N=157)

Adult

(N=134)

Pediatric

(N=23)

Age (years), Mean ± SD 43.6 ± 12.6 39.2 ± 15.3 43.3 ± 12.5 15.3 ± 1.4

Age <18 (n,%) 2 (7) 23 (15) 0 23 (100)

Sex (Female; n,%) 18 (60) 91 (58) 87 (65) 4 (17)

Race (n,%)

White (Caucasian) 26 (87) 119 (76) 110 (82) 9 (39)

Asian 1 (3) 26 (17) 19 (14) 7 (30)

Black or African American 3 (10) 5 (3) 2 (2) 3 (13)

Other 0 7 (4) 3 (2) 4 (17)

Weight (kg), Mean ± SD 83.5 ± 19.9 75 ± 18 77.4 ± 17.7 61.1 ± 13.7

Body Mass Index (kg/m2), Mean ± SD 29.6 ± 6.8 27 ± 5.9 27.5 ± 5.8 21.1 ± 3.0

<30 kg/m2, n (%) 17 (57) 115 (73) 92 (69) 23 (100)

≥30 kg/m2, n (%) 13 (43) 42 (27) 42 (31) 0

Systolic Blood Pressure (mmHg), Mean ± SD 120 ± 16 120 ± 13 121 ± 13 114 ± 11

Diastolic Blood Pressure (mmHg), Mean ± SD 76 ± 9 73 ± 10 75 ± 10 65 ± 8

Baseline eGFR (mL/min/1.73 m2), Mean ± SD 54 ± 24 63 ± 18 61 ± 18 70 ± 16

eGFR ≥ 60 mL/min/1.73 m2 12 (35) 92 (59) 73 (54) 19 (83)

eGFR 45 to 59 mL/min/1.73 m2 2 (7) 33 (21) 32 (24) 1 (4)

eGFR <45 mL/min/1.73 m2 11 (37) 32 (20) 29 (22) 3 (13)

Albumin to Creatinine Ratio (mg/g), Geometric mean ± SE 148 ± 50 141 ± 24 130 ± 24 231 ± 96

<30 mg/g, n (%) 8 (27) 39 (25) 36 (27) 3 (13)

30 to ≤ 300 mg/g, n (%) 10 (33) 46 (29) 39 (29) 7 (30)

>300 to ≤ 1000 mg/g, n (%) 7 (23) 36 (23) 31 (23) 5 (22)

>1000 mg/g, n (%) 5 (17) 36 (23) 28 (21) 8 (35)

Age at Alport Syndrome Diagnosis (years), Mean ± SD 29.3 ± 19.6 29.7 ± 17.9 33.0 ± 17.2 10.5 ± 5.1

Confirmed Genetic Diagnosis of Alport Syndrome, n (%) 28 (93) 148 (94) 128 (96) 20 (87)

Mode of Inheritance, n (%)

X-linked 23 (82) 98 (66) 84 (66) 14 (70)

Autosomal (Recessive or Dominant) 5 (18) 48 (32) 42 (33) 6 (30)

Unknown 0 2 (1) 2 (2) 0

Genotype, n (%)

COL4A3 mutation 3 (11) 19 (13) 16 (13) 3 (15)

COL4A4 mutation 7 (25) 35 (24) 31 (24) 4 (20)

COL4A5 mutation 22 (79) 100 (68) 86 (67) 14 (70)

ACE-inhibitor/ARB Treatment, n (%) 25 (83) 122 (78) 105 (78) 17 (74)

https://rarediseases.org/rare-diseases/alport-syndrome/

Safety and Efficacy of Bardoxolone Methyl in Patients with Rare Chronic Kidney Diseases

• Chronic kidney disease (CKD) develops

due to multiple pathogenic processes that

cause injury to cells, disruption of

structure, and reduction in function,

eventually leading to end-stage kidney

disease (ESKD)1-3

• Despite diverse etiology, inflammation is

a common mechanism underlying the

development and progression of CKD3

BACKGROUND

PEP, GBA and CW are consultants to Reata Pharmaceuticals.

GAB, CJM, MPC, MOG and AG are employees of Reata Pharmaceuticals.

GBA, LAI, DVR, and ALS receive research funding from Reata Pharmaceuticals.

DISCLOSURES

FP117

B

BARDOXOLONE METHYL

• Bardoxolone methyl (Bard) is an investigational small-molecule drug that, by activation of

Nrf2, promotes resolution of inflammation, reduction of oxidative stress, and improved

mitochondrial function4

• Bard increases GFR acutely by reducing inflammatory signaling and restoring Kf in

animal models5,6

• Bard increases GFR chronically by reducing remodeling and fibrosis in animal models of

hyperfiltration, hypertension, diabetes, lupus, and protein overload7-11

• In 11 clinical trials, Bard increased measured or estimated GFR (eGFR)12-20

• Bard reduced markers of vascular inflammation and injury, including angiotensin II,

circulating endothelial cells (CECs), IFNγ and vascular adhesion molecules21,22

• Increases in eGFR have been durable for up to two years on-treatment and

improvements post-withdrawal have been observed for up to 8 weeks after

withdrawal14-18

Bard Analog RTA dh404 Restored Nrf2 Activation and Suppressed Inflammation,

Remodeling, and Fibrosis in 5/6 Nephrectomy Model of Hyperfiltration

Nrf2 TGF-β FibrosisNF-κB

BASELINE CHARACTERISTICS

• PHOENIX enrolled 103 patients who had lost roughly one-half of their kidney function prior

to study entry

• Patients had progressive loss of eGFR despite optimized RAASi therapy and low UACR

SAFETY: ADVERSE EVENTS

Preferred Term Total (n=103)

Muscle spasms 44 (43%)

Headache 14 (14%)

Fatigue 12 (12%)

Summary of Adverse Events*

*AEs reported in >10% patients

• 92/103 (89%) patients completed treatment

through Week 12

• Bard generally well-tolerated with only 7 (6.8%)

patients permanently discontinuing due to

adverse events (AE)

• AE profile consistent with prior trials

• Most common AE reported was muscle spasms,

which were not associated with increases in

creatine kinase or evidence of muscle toxicity23

• No Bard or fluid-related serious AEs (SAE)

URINARY ALBUMIN TO CREATININE RATIO

• Patients optimized on available

therapies upon study entry as

evidenced by low urinary protein

within international treatment guideline

goals (<1,000 mg/g)

• Bard treatment did not significantly

increase UACR in any cohort

• Phase 2, open-label, multi-center, US-only trial (NCT03366337)

— Four separate cohorts of patients with ADPKD, IgAN, T1D CKD, or FSGS

— Targeted enrollment of 25 to 30 patients per cohort

• Primary endpoint: change in eGFR from baseline at Week 12

• Key eligibility: eGFR ≥ 30 to ≤ 90 mL/min/1.73 m2; 18-65 years old; urinary albumin to

creatinine ratio (UACR) ≤ 2500 mg/g

PHOENIX STUDY DESIGN

FUTURE DIRECTIONS

• Bard has demonstrated significant improvements in eGFR in patients with diverse etiologies of

CKD and across a broad range of kidney function

• Bard is also currently being studied in:

— CARDINAL: Phase 2/3 study in patients with Alport syndrome

— FALCON: Phase 3 placebo-controlled trial of Bard in patients with ADPKD

— AYAME: Phase 3 outcomes study in Japanese patients with diabetic CKD

• Bard significantly increased eGFR in patients in all four different rare forms of CKD

• No statistically or clinically significant increase in albuminuria in any cohort

• No increases in mean blood pressure or evidence of fluid overload in any cohort

• Bard was well-tolerated without any drug-related SAEs

CONCLUSION

EFFICACY: eGFR

• Bard significantly increased eGFR by 7.8 mL/min/1.73 m2 at Week 12

• eGFR increased in 88% of patients at Week 12

VITAL SIGNS

1. Lopez-Hernandez and Lopez-Novoa. Cell Tissue

Res. 2012, 347(1): 141-54.

2. Fogo and Kon. Int J Biochem Cell Biol. 2010 42(9):

1388-97.

3. Yamaguchi et al. F1000Res. 2015 4:1212.









REFERENCES



14. Pergola et al. N Engl J Med. 2011, 365(4):327-36









23. Block, et al. J Am Soc Nephrol. 2017, 28:B3 Abstract

Presented at ERA-EDTA, June 14, 2019; Budapest, HungaryBardoxolone methyl is an investigational drug. Safety and efficacy have not been established by any agency.

Pablo E. Pergola, MD, PhD; Anjali Acharya, MD; Gerald B. Appel, MD; Ahmed M. Awad, DO; Judith A. Betts, MD;

Geoffrey A. Block, MD; Melanie Chin, PhD; Angie Goldsberry, MS; Lesley A. Inker, MD; Colin J. Meyer, MD; Anjay

Rastogi, MD, PhD; Dana V. Rizk, MD; Kevin Schroeder, MD; Christoph Wanner, MD; Arnold L. Silva, MD, PhD

Systolic BPDiastolic BP

• Bard significantly reduced systolic and diastolic blood pressure at Week 12

• No changes in diuretic usage

• No correlation between changes in blood pressure and changes in eGFR

UACR Over Time

CharacteristicAll

(n=103)

ADPKD

(n=31)

IgAN

(n=26)

T1D-CKD

(n=28)

FSGS

(n=18)

Age, years (mean ± SD) 48 ± 10 47 ± 9 49 ± 10 49 ± 10 49 ± 13

Baseline eGFR, mL/min/1.73 m2 (mean ± SE) 53 ± 2 48 ± 2 46 ± 2 68 ± 3 52 ± 4

Baseline UACR, mg/g (geometric mean) 63.9 44.4 104.0 30.9 184.3

Receiving ACEi or ARB (n,%) 85 (83%) 24 (77%) 25 (96%) 19 (68%) 17 (94%)

Average yearly historical eGFR loss

(mL/min/1.73 m2)-2.8 -4.5 -1.2 -1.9 -2.6

*Defined as proportion of patients reaching Week 12 with eGFR values above

baseline at Week 12


(mL/min/1.73 m2)N ∆eGFR (mL/min/1.73 m2)

CARDINAL Alport syndrome 30 – 90 30 13.4 (p<0.001)1

PHOENIX ADPKD 30 – 90 31 9.3 (p<0.001)1

PHOENIX IgAN 30 – 90 26 8.0 (p<0.001)1

PHOENIX T1D CKD 30 – 90 28 5.5 (p=0.02)1

PHOENIX FSGS 30 – 90 18 7.8 (p=0.003)1




402-C-0902 T2D CKD 15 – 45 131 6.5 (p<0.001)1


eGFR Over Time

Distribution of eGFR

Changes

CohortWeek 12 Response

Rate*

ADPKD 96%

IgAN 91%

T1D-CKD 75%

FSGS 88%

All 88%

N=103 N=101 N=95 N=91

EFFICACY: eGFR

• Bard significantly increased eGFR by 7.8 mL/min/1.73 m2 at Week 12

• Increase represents recovery of three prior years of loss based on historical data

eGFR Over Time Distribution of eGFR Changes

-10

-5

0

5

10

15

20

25

30

35

We

ek 1

2 e

GF

RC

han

ge

(m

L/m

in/1

.73 m

2)

Safety and Efficacy of Bardoxolone Methyl in Patients with Focal Segmental GlomerulosclerosisPablo E. Pergola, MD, PhD; Anjali Acharya, MD; Ahmed M. Awad, DO; Geoffrey A. Block, MD; Melanie P.

Chin, PhD; Angie Goldsberry, MS; Colin J. Meyer, MD; Kevin Schroeder, MD; Arnold L. Silva, MD, PhD

• Etiology of primary focal segmental glomerulosclerosis (FSGS) is either unknown or

caused by mutations that result in podocyte injury and subsequent inflammation,

fibrosis, and progressive loss of kidney function

• One of the most common forms of chronic glomerular disease with approximately

40,000 patients in US1

• No approved therapies for FSGS

— Annual average decline of 2.4 mL/min/1.73 m2

— Increasingly common cause of end-stage kidney disease (ESKD)

FOCAL SEGMENTAL GLOMERULOSCLEROSIS

PEP is a consultant to Reata Pharmaceuticals.

GAB, CJM, MPC, MOG and AG are employees of Reata Pharmaceuticals.

ALS and PEP receive research funding from Reata Pharmaceuticals.

DISCLOSURES

FP152

B

BARDOXOLONE METHYL

• Bardoxolone methyl (Bard) is an investigational small-molecule drug that, through

activation of Nrf2, promotes resolution of inflammation, reduction of oxidative

stress, and improved mitochondrial function3

• Bard increases GFR acutely by reducing inflammatory signaling and restoring Kf in

animal models4,5

• Bard increases GFR chronically by reducing remodeling and fibrosis in animal

models of hyperfiltration, hypertension, diabetes, lupus, and protein overload6-10

• In 11 clinical trials, Bard increased measured or estimated GFR (eGFR)11-19

• Bard has been shown to reduce markers of vascular inflammation and injury,

including angiotensin II, circulating endothelial cells (CECs), IFNγ and vascular

adhesion molecules20,21

• Increases in eGFR have been durable for up to two years on-treatment and

improvements post-withdrawal have been observed for up to 8 weeks after

withdrawal13-17

Bard Analog RTA dh404 Restored Nrf2 Activation and Suppressed Inflammation,

Remodeling, and Fibrosis in 5/6 Nephrectomy Model of Hyperfiltration

Nrf2 TGF-β FibrosisNF-κB

BASELINE CHARACTERISTICS

CharacteristicTotal

(n=18)

Age, years (mean ± SD) 49 ± 13

Baseline eGFR, mL/min/1.73 m2 (mean ± SE) 52 ± 4

Baseline UACR, mg/g (geometric mean) 184.3

Receiving RAASi (n,%) 17 (94%)

Average yearly historical eGFR loss (mL/min/1.73 m2) -2.6

• PHOENIX enrolled 18 patients with biopsy-confirmed FSGS

• Historical eGFR data showed patients had progressive loss of eGFR despite

optimized RAASi therapy and low urinary albumin to creatinine ratio (UACR)

• Patients had lost roughly one-half of their kidney function prior to study entry

• Phase 2, open-label, multi-center, US-only trial (NCT03366337)

• Four separate cohorts of patients with ADPKD, IgAN, T1D CKD, or FSGS

• Primary endpoint: change in eGFR from baseline at Week 12

• Key eligibility: eGFR ≥ 30 to ≤ 90 mL/min/1.73 m2; 18-65 years old; UACR ≤ 2500 mg/g

PHOENIX STUDY DESIGN

CONCLUSION

• Bard significantly increased eGFR in patients with FSGS

• Bard did not increase albuminuria

• Bard was generally well-tolerated without any drug-related SAEs

• Additional studies are needed to assess the longer-term effects of Bard on eGFR in

patients with FSGS

1. Sim et al. Am J Kidney Dis. 2016, 68(4):533-544

2. Sim et al. Mayo Clin Proc. 2018, 93(2):167-178











REFERENCES13. Pergola et al. N Engl J Med. 2011, 365(4):327-36









22. Chertow et al. J Diabetes Complications 2018, 32(12):1113-

1117

23. Saha et al. J Biol Chem 2010, 285(52):40581-40592

24. Block, et al. J Am Soc Nephrol. 2017, 28:B3 Abstract

Presented at ERA-EDTA, June 14, 2019; Budapest, HungaryBardoxolone methyl is an investigational drug. Safety and efficacy have not been established by any agency.

URINARY ALBUMIN TO CREATININE RATIO

• Patients optimized on available

therapies upon study entry as

evidenced by low urinary protein within

international treatment guideline goals

(<1,000 mg/g)

• Unlike other FSGS trials, no minimum

level of proteinuria was required

• Baseline UACR levels were generally

low likely due to all but one patient

receiving RAASi upon study entry

• Bard treatment resulted in no significant

change in UACR

UACR Over Time

VITAL SIGNS• Blood pressure stable and within normal limits during treatment

• Consistent with prior studies, slight decreases in weight observed22, which is likely due to loss of

adiposity without loss of muscle mass22,23

BP Over Time Weight Over Time

SAFETY: ADVERSE EVENTS

Preferred TermTotal

(n=18)

Muscle spasms 9 (50%)

Constipation 3 (17%)

Nasopharyngitis 3 (17%)

*AEs reported in >15% patients

• 17/18 (94%) patients completed treatment

through Week 12

• Bard generally well-tolerated with only 1 (6%)

patient permanently discontinuing due to AEs

• AE profile consistent with prior trials

• Most common AE reported was muscle spasms,

which were not associated with increases in CK

or markers of muscle toxicity24

• No Bard or fluid-related SAEs

Summary of Adverse Events*

FUTURE DIRECTIONS

• Bard has demonstrated significant improvements in eGFR in patients with diverse etiologies of

CKD and across a broad range of kidney function

• Bard is also currently being studied in:

— CARDINAL: Phase 2/3 study in patients with Alport syndrome

— FALCON: Phase 3 placebo-controlled trial of Bard in patients with ADPKD

— AYAME: Phase 3 outcomes study in Japanese patients with diabetic CKD


(mL/min/1.73 m2)N ∆eGFR (mL/min/1.73 m2)

CARDINAL Alport syndrome 30 – 90 30 13.4 (p<0.001)1

PHOENIX ADPKD 30 – 90 31 9.3 (p<0.001)1

PHOENIX IgAN 30 – 90 26 8.0 (p<0.001)1

PHOENIX T1D CKD 30 – 90 28 5.5 (p=0.02)1

PHOENIX FSGS 30 – 90 18 7.8 (p=0.003)1




402-C-0902 T2D CKD 15 – 45 131 6.5 (p<0.001)1


N=18 N=18 N=17 N=16

fp179 baseline characteristics of the “cardinal” trial...conclusion baseline characteristics of...

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