Astrazeneca Plc · LSE:AZN
Astrazeneca — American Society of Nephrology Kidney Week 2019
43 slides from Astrazeneca's conference presentation, Nov 10, 2019
Slide 1: Investor science call: American Society of Nephrology Kidney Week 2019
Investor science call: American Society of Nephrology Kidney Week 2019 Conference call for investors and analysts 10 November 2019
Slide 2: Forward-looking statements
Forward-looking statements In order, among other things, to utilise the 'safe harbour' provisions of the US Private Securities Litigation Reform Act 1995, we are providing the following cautionary statement: this document contains certain forward-looking statements with respect to the operations, pe
Slide 3: Agenda
Agenda Unmet medical need Roxadustat Phase III OLYMPUS and ROCKIES trials Roxadustat Phase III ‘pooled’ safety and efficacy Commercial opportunity Q&A 3
Slide 4: 2019: a very busy year for the pipeline
2019: a very busy year for the pipeline Investor science events in each therapy area Oncology Cardiovascular, renal Respiratory and metabolism (and immunology) American Society of European Society of American College of Clinical Oncology (Jun) Cardiology (Sep) Rheumatology (Nov) • Meet AZN managemen
Slide 5: Presenters
Presenters Elisabeth Bjork John Houghton Joris Silon Senior Vice President, Global Medicines Leader, Senior Vice President, BioPharmaceuticals R&D, BioPharmaceuticals R&D, BioPharmaceuticals Business Unit, CVRM roxadustat CVRM Dr Steven Fishbane Dr Robert Provenzano Zucker School of Medicine at Asso
Slide 6: Agenda
Agenda Unmet medical need Roxadustat Phase III OLYMPUS and ROCKIES trials Roxadustat Phase III ‘pooled’ safety and efficacy Commercial opportunity Q&A 6
Slide 7: 200 million adult patients have chronic kidney disease
Anaemia can be a serious medical condition; it is associated with increased risk of hospitalisation, cardiovascular (CV) complications and death Past 200 million adult patients have chronic kidney disease (CKD) worldwide 7
Slide 8: Roxadustat is a first in class HIF-PH inhibitor
Roxadustat is a first in class hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor CKD anaemia is currently characterised as erythropoietin (EPO) and iron deficiency Past Patients receive EPO supplements and extra iron to encourage erythrocyte production Patients were previously treated w
Slide 9: Roxadustat has the potential to revolutionise the treatment paradigm
Treating CKD anaemia enables the body to stimulate complete erythropoiesis Future Roxadustat has the potential to revolutionise the treatment paradigm of patients with anaemia from CKD 9
Slide 10: Agenda
Agenda Unmet medical need Roxadustat Phase III OLYMPUS and ROCKIES trials Roxadustat Phase III ‘pooled’ safety and efficacy Commercial opportunity Q&A 10
Slide 11: Roxadustat Phase III ROCKIES trial
Roxadustat Phase III ROCKIES trial 11
Slide 12: Design: Phase 3, Randomized, Open Label, Active Controlled
Design: Phase 3, Randomized, Open Label, Active Controlled Patients with Dose titrated to Oral roxadustat TIW anemia of CKD Hb 11±1 g/dL R on hemo- or 1:1 peritoneal Dosed per Parenteral epoetin alfa dialysis prescribing information Week –6 2 20 EOT EOS Visits Screening 1st wk Every 2nd wk Every 4th
Slide 13: Patient Disposition
Patient Disposition Patients enrolled Patients randomized N=2941 N=2133 Roxadustat Epoetin alfa Excluded from Excluded from analysis due to n=1068 n=1065 analysis due to GCP violations GCP violations n=17 Received Tx Received Tx n=10 n=1048 n=1053 Discontinued Tx n=352 Study withdrawal n=69 Disconti
Slide 14: Primary Efficacy Endpoint for US: Hb Change from Baseline
Primary Efficacy Adverse Events inEndpoint for US: Hb Change from the Population* Baseline to Average Hb in Weeks Roxadustat 28–52 (N=1048) Epoetin alfa (N=1053) AE category N pts w/ N per N pts w/ N per % % event 100 P-Y event 100 P-Y Any AE 891 85.0 P=0.036 168.2 890 84.5 132.5 Any AE leading 0.9
Slide 15: Adverse Events in the Population
Adverse Events in the Population* Roxadustat (N=1048) Epoetin alfa (N=1053) AE category N pts w/ N per N pts w/ N per % % event 100 P-Y event 100 P-Y Any AE 891 85.0 168.2 890 84.5 132.5 Any AE leading to 57 5.4 3.1 26 2.5 1.2 discontinuation of drug Any serious AE 604 57.6 49.2 606 57.5 43.5 All-ca
Slide 16: Common AEs and SAEs in the Population
Common AEs and SAEs in the Population* Roxadustat (N=1048) Epoetin alfa (N=1053) AE category N pts w/ N per N pts w/ N per % % event 100 P-Y event 100 P-Y Most reported AEs Diarrhea 117 11.2 6.8 107 10.2 5.5 Hypertension 92 8.8 5.3 94 8.9 4.8 Pneumonia 91 8.7 5.1 101 9.6 5.0 Headache 82 7.8 4.7 57 5
Slide 17: Roxadustat Phase III OLYMPUS trial
Roxadustat Phase III OLYMPUS trial 17
Slide 18: Design: Phase 3, Double-Blind, Randomized
Design: Phase 3, Double-Blind, Randomized Hb <10 g/dL with Started at 70 mg TIW, Stage 3, 4 or 5 R Oral roxadustat titrated to Hb 10–12 g/dL CKD not 1:1 Oral placebo on dialysis Week –6 2 20 52 EOT EOS Visits Screening 1st wk Every 2nd wk Every 4th wk Every 8th wk Period Screening Treatment (up to 4
Slide 19: Patient Disposition
Patient Disposition Patients enrolled Patients randomized N=5222 n=2781 Roxadustat Placebo Excluded from Excluded from analysis due to n=1393 n=1388 analysis due to GCP violations GCP violations n=9 Received Tx Received Tx n=11 n=1384 n=1376 Discontinued Tx n=499 Study withdrawal n=84 Discontinued T
Slide 20: Primary Efficacy Endpoint for US: Change in Hemoglobin
Primary Efficacy Endpoint for US: Change in Hemoglobin from Baseline to the Average Over Weeks 28–52 P<0.001 2.0 1.75 Adjusted LSM change 1.8 1.6 in Hb (g/dL) 1.4 1.2 1.0 0.8 0.6 0.40 0.4 0.2 0.0 Roxadustat (n=1334) Placebo (n=1330) Intent-to-treat analysis set. Error bars are 95% confidence interva
Slide 21: Adverse Events (ITT)
Adverse Events (ITT*) Roxadustat (N=1384) Placebo (N=1377) OLYMPUS Events N pts % N per N pts % N per w/ event 100 P-Y† w/ event 100 P-Y† Any AE 1243 89.8 182.9 1216 88.3 171.9 Any AE leading to 78 5.6 2.8 57 4.1 2.1 discontinuation of drug Any serious AE 795 57.4 42.1 749 54.4 40.0 All-cause mortal
Slide 22: Common Adverse Events (ITT)
Common Adverse Events (ITT*) Roxadustat (N=1384) Placebo (N=1377) AE category N pts % N per N pts % N per w/ event 100 P-Y† w/ event 100 P-Y† Most reported AEs End stage renal disease 209 21.0 11.7 282 20.5 11.8 Urinary tract infection 177 12.8 6.8 110 8.0 4.2 Pneumonia 165 11.9 6.2 130 9.4 4.9 Hype
Slide 23: Conclusions for both trials
Conclusions for both trials ROCKIES OLYMPUS • Compared with epoetin alfa, roxadustat: • Compared with placebo, roxadustat treatment: • Increased Hb at least as effectively in dialysis patients • Significantly increased Hb levels with anaemia • regardless of iron-repletion • Increased Hb more effecti
Slide 24: Agenda
Agenda Unmet medical need Roxadustat Phase III OLYMPUS and ROCKIES trials Roxadustat Phase III ‘pooled’ safety and efficacy Commercial opportunity Q&A 24
Slide 25: Roxadustat Phase III 'pooled' safety and efficacy
Roxadustat Phase III ‘pooled’ safety and efficacy 25
Slide 26: Roxadustat NDD and DD Program
Roxadustat NDD and DD Program Phase 3 CKD non-dialysis-dependent (NDD) Pool D5740C00001 FGCL-4592-060 1517-CL-0608 NDD Pooled OLYMPUS ANDES ALPS Number of patients: 4277 AstraZeneca FibroGen Astellas Roxa Placebo N=2761 N=922 N=594 N=2391 N=1886 Patient exposure years: 6194 1.62 1.23 R 1:1 R 2:1 R 2
Slide 27: Roxadustat NDD Program: Evaluation of Anemia Therapy in a Broad Range of Patients
Roxadustat NDD Program: Evaluation of Anemia Therapy In A Broad Range ofwith Scatter plot Patients NotBaseline correlation between Included In Prior CKD Anemia Trials eGFR & HB Baseline NDD Studies 11.0 10.5 Roxadustat NDD Patient Features 10.0 Advanced CKD: 42% CKD 5 9.5 Low Iron stores: 40% non-ir
Slide 28: NDD Efficacy: Met Primary Efficacy Endpoint
NDD Efficacy: Met Primary Efficacy Endpoint Roxadustat is superior to placebo, regardless of iron-repletion Primary efficacy endpoint (change in Hb from baseline to Hb averaged over Weeks 28–52) was met in individual studies and pooled analyses Hb change from baseline to Week 28–52 NDD (N=4277): Mea
Slide 29: DD: Roxadustat Efficacious, Larger Hb Increase Than EPO
DD: Roxadustat Efficacious, Larger Hb Increase Than EPO in Individual Studies & In Pooled Analysis Primary efficacy endpoint (change in Hb from baseline to Hb averaged over Weeks 28 to 52): Roxadustat achieved larger Hb increase over epoetin alfa in individual studies & in pooled DD Hb (g/dL) change
Slide 30: NDD Pool: Cardiovascular Safety Endpoints
NDD Pool: Cardiovascular Safety Endpoints MACE, MACE+, All-cause Mortality Risks of MACE, MACE+, or all-cause mortality in roxadustat patients were comparable to placebo in NDD patients* Proportion of Patients Without MACE** Time to event endpoints using Cox model, ITT analysis** 1.0 NDD (OLYMPUS, A
Slide 31: DD Pooled: Cardiovascular Safety Endpoints
DD Pooled: Cardiovascular Safety Endpoints • Risk of MACE and all cause mortality in roxadustat patients were not increased compared to epoetin alfa in DD patients* • Roxadustat patients had a lower risk of MACE+ than epoetin alfa patients Time to event endpoints using Cox model, on-treatment analys
Slide 32: Incident Dialysis Pool: Cardiovascular Safety Endpoints
Incident Dialysis Pool: Cardiovascular Safety Endpoints Roxadustat had 30% lower risk of MACE and 34% lower risk of MACE+ than epoetin alfa* and with a trend towards lower all-cause mortality relative to epoetin alfa, in incident dialysis patients Time to event endpoints using Cox model Proportion o
Slide 33: Conclusions: Efficacy
Conclusions: Efficacy • Roxadustat efficacy was demonstrated – Achieved primary efficacy endpoint (change in Hb) in individual studies and pooled analyses • NDD: roxadustat was superior to placebo and efficacious regardless of iron-repletion • DD: roxadustat achieved larger mean Hb increase than epo
Slide 34: Conclusions: Roxadustat CV Safety
Conclusions: Roxadustat CV Safety • CV safety was demonstrated in all study populations – Non-dialysis: Risk of MACE, MACE+, and all-cause mortality in roxadustat patients were comparable to placebo in NDD patients – Incident dialysis: Roxadustat had 30% lower risk of MACE and 34% lower risk of MACE
Slide 35: Agenda
Agenda Unmet medical need Roxadustat Phase III OLYMPUS and ROCKIES trials Roxadustat Phase III ‘pooled’ safety and efficacy Commercial opportunity Q&A 35
Slide 36: How does roxadustat compare to currently approved treatments for anaemia from CKD?
How does roxadustat compare to currently approved treatments for anaemia from CKD in NDD or DD patients? 36
Slide 37: How do you see roxadustat fitting into the CKD treatment paradigm?
How do you see roxadustat fitting into or potentially changing the CKD treatment paradigm? 37
Slide 38: What factors will enable more patients to benefit from roxadustat?
What factors will enable more patients, who require treatment of anaemia from CKD in NDD or DD, to benefit from roxadustat in the future? 38
Slide 39: Chronic kidney disease: prevalence of anaemia increases as disease progresses
Chronic kidney disease The prevalence of anaemia increases as the disease progresses 100 United States1 30 million 2 19 million 2 80 US prevalence of patients US prevalence of patients with CKD with CKD (Stage 3-5) % of patients 60 4 million 2 million 40 20 2 2 0 US diagnosed patients with US treate
Slide 40: US regulatory submission in Q4 2019
Demonstrated CV safety in pooled analysis8-9 Consistent Hb control across all patients1-6 Effect is US regulatory independent of underlying inflammation1, 7 Roxadustat submission in Q4 2019 Reduces the potential need for IV iron administration3 Source: 1. Provenzano R, et al. Am J Kidney Dis 2016;67
Slide 41: Agenda
Agenda Unmet medical need Roxadustat Phase III OLYMPUS and ROCKIES trials Roxadustat Phase III ‘pooled’ safety and efficacy Commercial opportunity Q&A 41
Slide 42: Q&A
Q&A
Slide 43: Use of AstraZeneca conference call, webcast and presentation slides
Use of AstraZeneca conference call, webcast and presentation slides The AstraZeneca webcast, conference call and presentation slides (together the ‘AstraZeneca Materials’) are for your personal, non-commercial use only. You may not copy, reproduce, republish, post, broadcast, transmit, make availabl
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