Akebia Therapeutics, Inc. · NASDAQ:AKBA
Akebia Therapeutics — Investor Presentation (October 2020)
44 slides from Akebia Therapeutics's investor presentation, Oct 23, 2020
Slide 1: ASN Investor Briefing Webcast
Akebia THERAPEUTICS BETTERING THE LIVES OF PEOPLE IMPACTED BY KIDNEY DISEASE ASN Investor Briefing Webcast October 23, 2020
Slide 2: Forward-looking statements
Statements in this presentation regarding Akebia’s strategy, plans, prospects, the markets and communities in which we and our partners, collaborators, vendors expectations, beliefs, intentions and goals are forward-looking statements within and customers operate; manufacturing and quality risks; ri
Slide 3: Agenda
AGENDA Opening Remarks John P. Butler, President and Chief Executive Officer Review of INNO2VATE and PRO2TECT Global Phase 3 Data Presented at American Society of Nephrology Kidney Week 2020 Reimagined Glenn Chertow, M.D., M.P.H., Professor of Medicine, Chief of the Division of Nephrology at Sta
Slide 4: INNO2VATE Program: Phase 3 Trials in Dialysis-Dependent CKD
INNO2VATE Program Global Phase 3 Clinical Trials of Vadadustat for Treatment of Anemia in Patients With Dialysis- Dependent Chronic Kidney Disease
Slide 5: Introduction
Introduction Background • Vadadustat is an investigational oral HIF-PHI under development for the treatment of anemia of CKD1 – In phase 2 studies, vadadustat raised and maintained hemoglobin concentrations within target range in patients with non dialysis-dependent (NDD-) and dialysis-dependent (DD
Slide 6: INNO2VATE Study Design
INNO2VATE Study Design • Two randomized, phase 3, global, multicenter, open-label, sponsor-blind, active-controlled noninferiority trials in incident DD-CKD and prevalent DD-CKD patients with similar design Vadadustat (oral tablets) dosed starting with 300 mg once daily, Randomized with flexible tit
Slide 7: Primary Safety and Efficacy Endpoints
Primary Safety and Efficacy Endpoints Safety Analysis - Combined Across Both, the Incident DD-CKD and the Prevalent DD-CKD Trial (Event Driven) Primary Safety Endpoint • Time to first adjudicated MACE (all-cause mortality, nonfatal myocardial infarction, or nonfatal stroke) – Noninferiority margin:
Slide 8: Baseline Demographics
Baseline Demographics Incident DD-CKD (N=369) Prevalent DD-CKD (N=3554) Vadadustat Darbepoetin alfa Vadadustat Darbepoetin alfa (N=181) (N=188) (N=1777) (N=1777) Characteristic Age, y, mean (SD) 56.5 (14.8) 55.6 (14.6) 57.9 (13.9) 58.4 (13.8) Male, no. (%) 107 (59.1) 113 (60.1) 990 (55.7) 1004 (56.5
Slide 9: Primary and Key Secondary Safety Endpoints
Primary and Key Secondary Safety Endpoints Vadadustat Darbepoetin Treatment Comparison Safety Endpoint HR (95% CI) (n/N) Alfa (n/N) Vadadustat/Darbepoetin Alfa MACE 355/1947 377/1955 0.96 (0.83, 1.11) Expanded MACE 420/1947 449/1955 0.96 (0.84, 1.10) Cardiovascular MACE 225/1947 242/1955 0.95 (0.80,
Slide 10: Time to First MACE Across Pre-Specified Subgroups
Time to First MACE Across Pre-Specified Subgroups Treatment Comparison Subgroup n/N (%) Vadadustat/Darbepoetin Alfa HR (95% CI) All (n=3902) 3902/3902 (100.0%) 0.96 (0.833, 1.113) Baseline Hb Level Low (n=1422) 1422/3902 (36.4%) 1.04 (0.822, 1.313) High (n=2480) 2480/3902 (63.6%) 0.91 (0.759, 1.100)
Slide 11: Summary of TEAEs and TEAEs Occurring in >10% of Patients
Summary of TEAEs and TEAEs Occurring in >10% of Patients in Either Treatment Group Incident DD-CKD, No. (%) Prevalent DD-CKD, No. (%) Vadadustat Darbepoetin alfa Vadadustat Darbepoetin alfa (N=179) (N=186) (N=1768) (N=1769) Any TEAEs 150 (83.8) 159 (85.5) 1562 (88.3) 1580 (89.3) Any TEAEs, drug-rela
Slide 12: Primary and Key Secondary Efficacy Endpoint
Primary and Key Secondary Efficacy Endpoint Mean changea from baseline in Hb levels in randomized populations Incident DD-CKD Trial Prevalent DD-CKD Trial Mean (SEM) change Vadadustat Darbepoetin Difference Mean (SEM) change Darbepoetin Difference from baseline, g/dL alfa (vadadustat - darbepoetin a
Slide 13: Summary and Conclusions
Summary and Conclusions Outcomes: Vadadustat was noninferior to darbepoetin alfa with respect to cardiovascular safety and hematological efficacy in patients on dialysis. Strengths Limitations • Large sample size (N=3923); • Investigators and patients not blinded for mean FU > 1.5 yrs treatment assi
Slide 14: PRO2TECT Program: Phase 3 Trials in Non-Dialysis-Dependent CKD
PRO2TECT Program Global Phase 3 Clinical Trials of Vadadustat for Treatment of Anemia in Patients With Non–Dialysis- Dependent Chronic Kidney Disease
Slide 15: PRO2TECT Study Design
PRO2TECT Study Design • Two randomized, phase 3, global, multicenter, open-label, sponsor-blind, active-controlled noninferiority trials compared vadadustat with darbepoetin alfa in patients with NDD-CKD: – ESA-untreated patients (“Correction”) OR ESA-treated patients (“Conversion”) – Target Hb leve
Slide 16: PRO2TECT Key Eligibility Criteria
PRO2TECT Key Eligibility Criteria PRO2TECT: ESA-untreated PRO2TECT: ESA-treated NDD-CKD NDD-CKD Age ≥18 years RBC transfusions No RBC transfusions within 8 weeks before randomization 8.0-11.0 g/dL (inclusive) US Baseline Hb level <10.0 g/dL 9.0-12.0 g/dL (inclusive) Non-US Currently maintained on ES
Slide 17: PRO2TECT Primary Safety and Efficacy Endpoints
PRO2TECT Primary Safety and Efficacy Endpoints Safety Analysis - Combined Across Both, the ESA-untreated NDD-CKD and the ESA-treated NDD-CKD Trial (Event Driven) Primary Safety Endpoint • Time to first adjudicated MACE (all-cause mortality, nonfatal myocardial infarction, or nonfatal stroke) – Nonin
Slide 18: PRO2TECT Baseline Characteristics
PRO2TECT Baseline Characteristics PRO2TECT: ESA-untreated NDD-CKD PRO2TECT: ESA-treated NDD-CKD Vadadustat Darbepoetin alfa Total Vadadustat Darbepoetin alfa Total Characteristic (N=879) (N=872) (N=1751) (N=862) (N=863) (N=1725) Age, y, mean (SD) 65.2 (14.3) 64.9 (13.7) 65.0 (14) 67.3 (13.1) 66.5 (1
Slide 19: PRO2TECT MACE, Expanded MACE, and Other Safety Endpoints
PRO2TECT MACE, Expanded MACE, and Other Safety Endpoints Safety Endpoint Vadadustat Darbepoetin Treatment Comparison HR (95% CI) (n/N) Alfa (n/N) Vadadustat/Darbepoetin Alfa MACE 382/1739 344/1732 1.17 (1.01, 1.36) Expanded MACEa 451/1739 424/1732 1.11 (0.97, 1.27) All-cause mortality 319/1739 307/1
Slide 20: PRO2TECT MACE, Expanded MACE, and Other Safety Endpoints
PRO2TECT MACE, Expanded MACE, and Other Safety Endpoints Vadadustat Darbepoetin Treatment Comparison Safety Endpoint HR (95% CI) (n/N) Alfa (n/N) Vadadustat/Darbepoetin Alfa MACE 382/1739 344/1732 1.14 (0.99, 1.32) Expanded MACEa 451/1739 424/1732 1.09 (0.95, 1.24) All-cause mortality 319/1739 307/1
Slide 21: PRO2TECT MACE by Region
PRO2TECT MACE by Region Prespecified Subgroup Analysis: US (N=1723) Prespecified Subgroup Analysis: Non-US (N=1748) 0.5 0.5 0.4 0.4 Cumulative Incidence of MACE Cumulative Incidence of MACE 0.3 0.3 0.2 0.2 0.1 0.1 Vadadustat Darbepoetin Alfa Vadadustat Darbepoetin Alfa 0.0 0.0 0 8 16 24 32 40 48 56
Slide 22: PRO2TECT MACE by Region
PRO2TECT MACE by Region MACE HR (95% CI) US (N=1723) Non-US (N=1748) MACE 1.01 (0.83, 1.23) 1.29 (1.03, 1.60) Expanded MACEa 0.99 (0.83, 1.17) 1.23 (1.00, 1.51) All-cause mortality 0.86 (0.69, 1.07) 1.27 (1.01, 1.60) Cardiovascular MACEb 1.16 (0.89, 1.52) 1.08 (0.78, 1.49) Cardiovascular mortality 0
Slide 23: PRO2TECT Hemoglobin Change From Baseline
PRO2TECT Hemoglobin Change From Baseline Mean change from baseline in Hb levels in randomized populations ESA-untreated NDD-CKD ESA-treated NDD-CKD 3.5 3.0 2.5 3.0 Mean Change from Baseline (+/-SD) Mean Change from Baseline (+/-SD) 2.0 2.5 1.5 in Hb (g/dL) 2.0 1.0 in Hb (g/dL) 1.5 0.5 0.0 1.0 -0.5 0
Slide 24: PRO2TECT Treatment-Emergent Adverse Events
PRO2TECT Treatment-Emergent Adverse Events ESA-untreated NDD-CKD, No. of subjects (%) ESA-treated NDD-CKD, No. of subjects (%) Vadadustat Darbepoetin alfa Vadadustat Darbepoetin alfa (N=878) (N=870) (N=861) (N=862) Any TEAE 798 (90.0) 797 (91.6) 767 (89.1) 756 (87.7) Any TEAE, drug-related 95 (10.8)
Slide 25: PRO2TECT Conclusions
PRO2TECT Conclusions Cardiovascular Safety: • Vadadustat did not meet the prespecified noninferiority criterion compared to darbepoetin alfa with respect to cardiovascular safety in patients with anemia and NDD-CKD • Adjusting for age as a continuous variable, the hazard ratio and the upper bound of
Slide 26: INNO2VATE and PRO2TECT Global Phase 3 Safety Data
INNO2VATE and PRO2TECT Global Phase 3 Safety Data
Slide 27: First Major Adverse Cardiovascular Events (MACE) by Program
First Major Adverse Cardiovascular Events (MACE) by Program INNO2VATE Global Events PRO2TECT Global Events N (%) N (%) Vadadustat Darbepoetin Vadadustat Darbepoetin MACE 355 (18.2) 377 (19.3) 382 (22.0) 344 (19.9) Death (all-cause mortality) 253 (13.0) 253 (12.9) 284 (16.3) 274 (15.8) Non-fatal MI 7
Slide 28: Cardiovascular Safety: PRO2TECT – Global, US and Ex-US
Cardiovascular Safety: PRO2TECT – Global, US and Ex-US Region was a randomization stratification variable and a prespecified subgroup analysis Age as a dichotomous variable (<65, ≥65) in the prespecified Cox model US (N=1723) Ex-US (N=1748) Global (N=3471) (Hb target 10-11 g/dL) (Hb target 10-12 g/d
Slide 29: Cardiovascular Safety: PRO2TECT – Global, US and Ex-US
Cardiovascular Safety: PRO2TECT – Global, US and Ex-US Region was a randomization stratification variable and a prespecified subgroup analysis Age rescaled as a continuous variable in the prespecified Cox model US (N=1723) Ex-US (N=1748) Global (N=3471) (Hb target 10-11 g/dL) (Hb target 10-12 g/dL)
Slide 30: Cardiovascular Safety: PRO2TECT MACE by Region (US and Ex-US)
Cardiovascular Safety: PRO2TECT MACE by Region (US and Ex-US) Region was a randomization stratification variable and a prespecified subgroup analysis Prespecified Subgroup Analysis: US (N=1723) Prespecified Subgroup Analysis: Ex-US (N=1748) Hb target 10-11 g/dL Hb target 10-12 g/dL MACE is a composi
Slide 31: Cardiovascular Safety: INNO2VATE, PRO2TECT and Combined in US
Cardiovascular Safety: INNO2VATE, PRO2TECT and Combined in US Region was a randomization stratification variable and a prespecified subgroup analysis Hb target in US was 10-11 g/dL Age rescaled as a continuous variable in the prespecified Cox model US INNO2VATE – DD-CKD US PRO2TECT – NDD-CKD US INNO
Slide 32: Cardiovascular Safety: INNO2VATE, PRO2TECT and Combined in Ex-US
Cardiovascular Safety: INNO2VATE, PRO2TECT and Combined in Ex-US Region was a randomization stratification variable and was prespecified subgroup analysis Hb target in Ex-US was 10-12 g/dL Age rescaled as a continuous variable in the prespecified Cox model Ex-US INNO2VATE – DD-CKD Ex-US PRO2TECT – N
Slide 33: Cardiovascular Safety: PRO2TECT in Ex-US by Average Hb Achieved
Cardiovascular Safety: PRO2TECT in Ex-US by Average Hb Achieved during Primary Evaluation Period* Achieved Hb ≤ 11 g/dL during PEP (N=751) Achieved Hb > 11 g/dL during PEP (N=811) Hb target 10-12 g/dL Hb target 10-12 g/dL 369 324 284 262 239 219 199 179 159 135 120 102 87 67 48 31 19 12 2 0 400 341
Slide 34: Cardiovascular Safety: PRO2TECT in Ex-US by Average Hb Achieved
Cardiovascular Safety: PRO2TECT in Ex-US by Average Hb Achieved during Primary Evaluation Period* Age rescaled as a continuous variable in the prespecified Cox model Ex-US PRO2TECT (Hb Target 10-12 g/dL) Achieved Hb ≤ 11 g/dL during PEP (N=751) Achieved Hb > 11 g/dL during PEP (N=811) Event N Event
Slide 35: Thank You!
Thank You! We would like to extend our sincerest appreciation to our investigators and their staff for participating in the INNO2VATE and PRO2TECT programs. Most importantly, thank you to our patients who participated in these programs. Because of their commitment, we are a step closer to fulfilling
Slide 36: Appendix
Appendix 36
Slide 37: Author Affiliations
Author Affiliations Glenn M. Chertow,1 Pablo E. Pergola,2 Rajiv Agarwal,3 Susan Arnold4, Gabriel Bako5, Geoffrey A. Block,6 Steven Burke,7 Fausto P. Castillo,8 Youssef MK Farag,7 Alan G. Jardine,9 Zeeshan Khawaja,7 Mark J. Koury,10 Eldrin F. Lewis,10 Tim Lin,11 Wenli Luo,7 Bradley J. Maroni,7† Kunih
Slide 38: INNO2VATE Program: Phase 3 Trials in Dialysis-Dependent CKD
INNO2VATE Program Global Phase 3 Clinical Trials of Vadadustat for Treatment of Anemia in Patients With Dialysis- Dependent Chronic Kidney Disease
Slide 39: Disclosures
Disclosures Funding • Funding for this trials was provided by Akebia Therapeutics, Inc., and Otsuka Pharmaceuticals Co. Ltd.. Syneos Health, funded by Akebia supported the development of this presentation Potential conflicts of interest • Dr. Eckardt reports grants from Amgen, AstraZeneca, Bayer, Fr
Slide 40: The HIF Pathway (Nobel-Prize 2019)
The HIF Pathway (Nobel-Prize 2019) The body’s response to low-oxygen environments is to increase cellular HIF protein levels to induce an orchestrated response to hypoxia, including enhanced EPO production and iron utilization Normal oxygen Hydroxylated HIFα Degradation HIF-α O2 HIF-Prolylhydroxylas
Slide 41: Acknowledgments
Acknowledgments The authors would like to thank the study investigators and staff for the conduct of this study and the patients for volunteering to participate in the two trials. 41
Slide 42: PRO2TECT Program: Phase 3 Trials in Non-Dialysis-Dependent CKD
PRO2TECT Program Global Phase 3 Clinical Trials of Vadadustat for Treatment of Anemia in Patients With Non–Dialysis- Dependent Chronic Kidney Disease
Slide 43: Disclosures
Disclosures Funding • Funding for this study was provided by Akebia Therapeutics, Inc., and Otsuka Pharmaceutical Development & Commercialization, Inc. Potential conflicts of interest • Dr. Chertow reports personal fees from Akebia during the conduct of the study 43
Slide 44: Acknowledgments
Acknowledgments The authors would like to thank the study investigators and staff for the conduct of this study and the patients for volunteering to participate in the study. The authors thank Sarah Garber, PharmD, an employee of Akebia Therapeutics, Inc., for her support in development of the prese
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