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AAO Media Briefing

AAO Media Briefing. AMD Trials and Treatments: An Evolving Landscape. ABDHISH R. BHAVSAR, M.D. Chair. Financial Disclosures. Abdhish R. Bhavsar , MD Research support - clinical trials: DRCR, Regeneron , Genentech. Agenda. Abdhish R. Bhavsar , MD: Welcome/Introductions

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AAO Media Briefing

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  1. AAO Media Briefing AMD Trials and Treatments: An Evolving Landscape ABDHISH R. BHAVSAR, M.D. Chair

  2. Financial Disclosures • AbdhishR. Bhavsar, MD • Research support - clinical trials: DRCR, Regeneron, Genentech

  3. Agenda • Abdhish R. Bhavsar, MD: Welcome/Introductions • PravinDugel, MD: Fovista 2b clinical trial results • Q/A • Abdhish R. Bhavsar, MD: Update CATT and Eylea • Susan Bressler, MD: Cataract sugery/AMD - no inc risk • Paul Mitchell, MD: Cataract surgery/AMD – inc risk • Edwin Stone, MD: Update on genetic testing for AMD • Media Q & A

  4. Study Disclosures • This study does include research conducted on human subjects • IRB approval has been obtained for each of the studies discussed.

  5. Investigation of Efficacy and Safety of Intravitreal Aflibercept Injection in Wet Age-Related Macular Degeneration (AMD) Abdhish R. Bhavsar, MD VIEW 1 VIEW 1 Integrated VIEW 2

  6. Study Design Multi-center, active controlled, double masked trial VIEW 1 N=1217; VIEW 2 N=1240 Patients randomized 1:1:1:1 IntravitrealAflibercept Ranibizumab 2 mg q8 wks 0.5 mg q4 wks 0.5 mg q4 wks 2 mg q4 wks Primary endpoint: Maintenance of Vision Secondary endpoint: Mean change in BCVA Dosing through Week 52Modified quarterly dosing through Week 96 *After 3 initial monthly doses

  7. Study Endpoints • Proportion of patients who maintained BCVA (%) (losing <15 ETDRS letters from baseline) PRIMARYENDPOINT • Mean change in BCVA as measured by ETDRS letter score from baseline • Proportion of patients who gained at least 15 letters of BCVA from baseline • Central Retinal Thickness KEYSECONDARYENDPOINTS BCVA: Best-Corrected Visual Acuity ETDRS: Early Treatment Diabetic Retinopathy Study

  8. ResultsWeek 52 VIEW 1 VIEW 1 Integrated VIEW 2

  9. ResultsWeek 52 – Week 96 VIEW 1 VIEW 1 Integrated VIEW 2

  10. Treatment Schedule • Re-treatment Criteria – • 12 weeks since previous injection • New or persistent fluid on OCT • Increase in CRT of ≥100 μm compared to the lowest previous value • Loss of ≥5 ETDRS letters from the best previous score in conjunction with recurrent fluid on OCT • New onset classic neovascularization • New or persistent leak on FA • New macular hemorrhage Solid = Injection Outline = Sham Hatched = Modified Quarterly Dosing

  11. Safety VIEW 1 VIEW 1 Integrated VIEW 2

  12. Summary • Afliberceptnoninferior to ranibizumab • Safety and efficacy was similar amongst the treatment groups

  13. Comparison of AMD Treatments Trials (CATT): Two Year Results Supported by Cooperative Agreements from the National Eye Institute, National Institutes of Health, DHHS Abdhish R. Bhavsar, MD for the Comparison of AMD Treatments Trials (CATT) Research Group

  14. Objectives • To determine the relative efficacy and safety of intravitreal ranibizumab and bevacizumab for treatment of neovascular AMD • To determine if less than monthly dosing of either drug compromises long term visual outcomes - Designed as two-year study with primary outcome at one year

  15. CATT Clinical Sites • 1185 patients with neovascular AMD enrolled at 43 sites in the United States 48

  16. Enrollment Criteria More Inclusive than Previous AMD Trials • CNV not required to be subfoveal as long as center involved by some component such as SRF, PED, or blood. • Allowed RAP lesions, juxtafoveal, and extrafoveal CNV • Allowed eyes with VA 20/25-20/320 • No limit on size of lesion

  17. Enrollment Criteria More Inclusive than Previous AMD Trials • Allowed eyes with >50% blood. All other entry criteria had to be met (VA 20/320 or better and can identify CNV on FA and fluid on OCT) 50

  18. CATT Treatment (Months) Year 2 Year 1 15 14 13 0 1 2 3 4 5 6 7 8 9 10 11 12 16 17 18 19 20 21 22 23 24 ranibizumabMonthly bevacizumab Monthly ranibizumabPRN bevacizumab PRN } Retreat if fluid on OCT or other signs of active CNV PrimaryEndpoint Finalvisit

  19. Treatment in PRN Arms • Treat to a dry OCT – zero tolerance for intraretinal, subretinal, or sub-RPE fluid. • May also treat if there is other evidence of CNV activity • New subretinal or intraretinal hemorrhage • Leakage or increased lesion size on FA • Unexplained decrease in visual acuity with no obvious atrophy or subretinal fibrosis. • No retinal thickness threshold (100 microns) as used in many neovascular AMD treatment studies.

  20. CATT Study Drugs Ranibizumab supplied locally similar to patients outside of the study Bevacizumab supplied by CATT repackaged in glass vials under IND

  21. Mean Change in Visual Acuity All Groups

  22. Mean Change in Total Retinal Thickness Over Time All Groups

  23. Percent with No Fluid at 1 Year

  24. Year 1 Adverse Events • No difference between drugs in rates of death, stroke, or myocardial infarction • Imbalance in total SAE’s (mostly hospitalizations): 24%bevacizumabvs 19% ranibizumab (p=0.04) • SAEs broadly distributed across all organ systems with differences present in areas not previously identified as areas of concern in systemic bevacizumab trials.

  25. Questions at End of Year 1 • Would ranibizumab and bevacizumab remain equivalent for visual acuity in Year 2? • Would wider visual acuity differences emerge between monthly and PRN dosing in Year 2? • Would the fluid differences between treatments noted in year 1 impact visual acuity with longer follow-up? • Would switching to PRN dosing after one year of monthly treatment maintain or adversely effect vision? • Would important safety differences emerge with longer follow-up?

  26. Two Year Results

  27. Patients • 1107 patients alive who continued in Year 2 • All available monthly treated patients in Year 1 (n=549) were successfully randomized to monthly or PRN treatment in Year 2 • Masking remained robust in Year 2 with identity of assigned drug known to ophthalmologist in only 66 of 12,645 evaluations (11 patients)

  28. Visual Acuity ResultsSame Regimen for Two Years

  29. Mean Change in Visual Acuity Same Regimen for Two years

  30. Patients Without 15Letter DecreaseSame Regimen for 2 Years

  31. Anatomical ResultsSame Regimen for Two Years

  32. Percent with No Fluid on OCT Same Regimen for 2 Years

  33. Typical Amount of Residual Fluid

  34. Percent with Geographic Atrophy Same Regimen for 2 Years

  35. Effect of Switching to PRN after One Year of Monthly Dosing

  36. Mean Change in Visual Acuity after Week 52 Monthly Always and Switched to PRN

  37. Percent with No Fluid on OCT Monthly Always and Switched to PRN

  38. Percent with Geographic Atrophy Monthly Always and Switched to PRN

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