Daiichi Sankyo Company, Limited · TSE:4568

Daiichi Sankyo — Technical Presentation (November 2014)

16 slides from Daiichi Sankyo's technical presentation, Nov 4, 2014

  1. Slide 1: Edoxaban in Atrial Fibrillation

    Edoxaban in Atrial Fibrillation Glenn Gormley, MD, PhD Senior Executive Officer and Global Head of R&D, Daiichi Sankyo Co., Ltd Nov. 4, 2014 Tuesday

  2. Slide 2: Background

    Background  Based on the results of ENGAGE AF-TIMI 48, Daiichi Sankyo submitted a New Drug Application on January 8th, 2014 and is currently seeking approval from the FDA for the use of Edoxaban to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation  Du

  3. Slide 3: Roles of Advisory Committee

    Roles of Advisory Committee  The FDA regularly seeks the advice of its advisory committees as it reviews New Drug Applications (NDA)  Purpose of the Advisory Committee meeting is to discuss any issues requested by FDA  Advisory Committee makes a recommendation to FDA on whether the NDA should be

  4. Slide 4: Outcome of the Meeting on Oct

    Outcome of the Meeting on Oct 30  CRD Advisory Committee voted 9 to 1 to recommend approval of once-daily Edoxaban for the reduction in risk of stroke and systemic embolic events (SEE) in patients with non-valvular atrial fibrillation (NVAF)  Daiichi Sankyo will work with the FDA during continued

  5. Slide 5: Features of ENGAGE AF-TIMI 48

    Features of ENGAGE AF-TIMI 48  Largest NOAC trial (21,105 patients)  Longest follow-up (2.8 years)  Best follow-up (1 patient without vital status)  Highest TTR (68.4%)  4-fold dose range (15 mg - 60 mg)  Once-daily dosage 4

  6. Slide 6: ENGAGE AF-TIMI 48 Trial Results

    ENGAGE AF-TIMI 48 Trial Results  ENGAGE met the primary efficacy endpoint of non- inferiority for stroke and SEE and superiority for the principal safety endpoint of major bleeding  ENGAGE demonstrated significant benefit of Edoxaban compared with warfarin across all key secondary outcomes and pre

  7. Slide 7: Edoxaban 60/30 mg vs Warfarin: Primary Endpoints Risk Differences

    Edoxaban 60/30 mg vs Warfarin Risk Differences for 10,000 Patients per Year Primary Endpoints—mITT On-Treatment 0 -5 Events/10,000 patients/year -6 -10 -15 -20 -25 -23 *** -30 -35 -32 * Stroke Hemorrhagic stroke Ischemic or SEE stroke * p < 0.05 6 *** p ≤ 0.001

  8. Slide 8: Edoxaban 60/30 mg vs Warfarin: Secondary Endpoints Risk Differences

    Edoxaban 60/30 mg vs Warfarin Risk Differences for 10,000 Patients per Year Secondary End Points—ITT Overall 0 Events/10,000 patients/year 0 -10 -5 -20 -30 -40 -36 -50 -60 -51 * -56 * -70 Stroke CV death All death Myocardial Fatal SEE infarction MI a death aFatal MI were 9 in 60/30 group and 9 in wa

  9. Slide 9: Focus of FDA Advisory Committee Subgroup Analyses

    Focus of FDA Advisory Committee Subgroup Analyses  A test for heterogeneity was used to evaluate whether observed treatment effects were consistent across various subgroups  2 out of 20 different subgroups evaluated demonstrated a significant interaction for efficacy ̶ Protocol defined analysis by

  10. Slide 10: Stroke or SEE by Baseline CrCL (pre-specified)

    Stroke or SEE by Baseline CrCL mITT On-Treatment Pre specified subgroup analysis (defined in Protocol) Edoxaban 60/30 mg vs warfarin  Edoxaban Warfarin  Creatinine clearance HR (95% CI) 60/30 mg better better 30 - ≤ 50 mL/min Warfarin Edoxaban 60/30 mg 0.88 (0.58, 1.32) > 50 mL/min Warfarin Edoxab

  11. Slide 11: Stroke or SEE by Baseline CrCL (exploratory)

    Stroke or SEE by Baseline CrCL mITT On-Treatment Exploratory subgroup analysis (not pre specified) Edoxaban 60/30 mg vs warfarin  Edoxaban Warfarin  HR (95% CI) 60/30 mg better better Moderate (30 - 50) 0.88 (0.58, 1.32) Mild (> 50 - < 80) 0.53 (0.40, 0.70) Normal (≥ 80) 1.41 (0.97, 2.06) 0.25 0.5

  12. Slide 12: NOAC Stroke or SEE Rates in Contemporary Trials

    NOAC Stroke or SEE Rates in Contemporary Trials Normal Renal Function Subgroup (CrCL ≥ 80 mL/min) FDA Briefing Document, table 65, page 156 1.4 NOAC stroke or SEE rate 1.2 Average NOAC event rate = 1.1 %/yeara 1.27 1.0 1.06 0.8 0.99 0.6 0.73 0.4 0.2 0.0 RE-LY ARISTOTLE ENGAGE ROCKET AF dabigatran ap

  13. Slide 13: Warfarin Stroke or SEE Rates in Contemporary Trials

    Warfarin Stroke or SEE Rates in Contemporary Trials Normal Renal Function Subgroup (CrCL ≥ 80 mL/min) FDA Briefing Document Table 65, p 156 1.6 Warfarin stroke or SEE rate 1.4 1.42 1.2 Average warfarin event rate = 1.1 /yra 1.0 1.12 1.03 0.8 0.6 0.76 0.4 0.2 0.0 RE-LY ARISTOTLE ENGAGE ROCKET AF Warf

  14. Slide 14: Stroke or SEE by CrCL Quintiles

    Adapted from FDA briefing document, table 2, p. 18 Stroke or SEE by CrCL Quintiles mITT On-Treatment Post-hoc subgroup analysis by CrCL quintiles 30 mg dose reduced 60-mg dosea 3.0 2.5 Event rate, %/yr (95%CI) Edoxaban Stroke or SEE 2.0 Warfarin 1.5 36/1434 1.0 20/1357 0.5 1.7 1.96 1.1 2.3 0.9 1.7 1

  15. Slide 15: Summary

    Summary  ENGAGE met the primary efficacy endpoint of non-inferiority for stroke and SEE and superiority for major bleeding  ENGAGE demonstrated significant benefit of Edoxaban compared with warfarin across all key secondary outcomes and predefined composite measures of net clinical outcome  In pa

  16. Slide 16: Conclusion

    Conclusion  The use of the Edoxaban 60/30 mg dose regimen for the proposed indication is safe and effective across the entire population of patients studied, including patients with normal renal function, and should be approved to reduce the risk of stroke and systemic embolism in patients with non

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