采視明 EYLEA Injection) 醫療科技評估報告

1 ( EYLEA Injection) - EYLEA aflibercept aflibercept 40 mg/ml, 1. ( 2mg aflibercept ) 2. ( H2O2 ) ( 2mg aflibercept ) (PCV) ( ) EYLEA wAMD ranibizumab 3 2 2mg aflibercept mL 12 4-12 102 CDR07012_ EYLEA 1/25 ranibizumab mg injection ranibizumab mg Phase III (VIEW-1 VIEW-2) aflibercept 2 mg injection ranibizumab mg injection 52 VIEW-1 VIEW-2 aflibercept ( ) (wAMD)

2 Ranibizumab PRN QALYs( ) 34,351 1) 2) aflibercept ranubizumab 1 EYLEA Lucentis / aflibercept /40mg/mL Ranibizumab/10mg/ml / 278 mcl/vial 165 mcl/syringe 102 CDR07012_ EYLEA 2/25 WHO/ATC S01LA05 S01LA04 (PCV) ( ) (1) ( ) (age-related macular degeneration, AMD) (2) (diabetic macular edema, DME) (3) ( ; branch or central retinal vein occlusion; BRVO CR O) 1. 2. 3. ~ 4. (1)50 ( ) (AMD) (101/5/1) I. 3 2 II.

3 FAG(fluorescein angiography) OCT(optical coherence tomography) polypoidal choroidal vasculopathy, PCV ICG (indocyanone green angiography) III. i. ii. AMD advanced geographic atrophy 102 CDR07012_ EYLEA 3/25 iii. (PCV) iv. (angioid streaks) AMD fovea Choroidal neovascularization CNV (101/5/1) (2) (diabetic macular edema, DME) (102/2/1) I. (central retinal thickness,CRT) 300 m II. (HbA1c) 10% III. 5 3 IV. i. FAG OCT (HbA1c) ii. 3 2 3 OCT (HbA1c) iii. ( HbA1c FAG OCT ) V.

4 I. (subfoveal) 102 CDR07012_ EYLEA 4/25 ii. AMD advanced geographic atrophy ( ) 33,467 mL ( ) ( )/ 12 1 3 AMD 5 Lucentis 1 1 3 100,401 ; 2 6 200,802 head-to-head comparison indirect comparison PBAC aflibercept ( EYLEA ) (fluorescein angiography) (AMD) (subfoveal) (choroidal 102 CDR07012_ EYLEA 5/25 neovascularization, CNV) optical coherence tomography OCT red free photography (March 2012) 8 ranibizumab ranibizumab aflibercept NICE SMC 2013 7 3 aflibercept ( EYLEA ) aflibercept ( EYLEA ) ( )

5 2013 8 15 CADTH/pCODR CADTH Canadian Agency for Drugs and Technologies in Health pCODR pan-Canadian Oncology Drug Review 2010 CADTH PBAC Pharmaceutical Benefits Advisory Committee NICE National Institute for Health and Care Excellence 102 CDR07012_ EYLEA 6/25 ( EYLEA ) : 102 8 27 42 (age-related macular degeneration, AMD) 55 65 AMD A E [1,2] 50 AMD (incidence) 1/100 65 75 (prevalence)

6 100/1,000 75 300 ~ 800/1,000[1] UK wet AMD 26,000 [8] 2004 AMD 50 1~2 [3] 2008 65 [15] 102 CDR07012_ EYLEA 7/25 AMD Amsler grid Fluorescein angiography Amsler grid grid grid Fluorescein angiography [1] AMD drusen drusen (retinal pigment epithelium, RPE) atrophic form macular degeneration ( dry type) exudative form ( wet type) ( ) AMD 90% AMD AMD 10% (choroidal neovascularization, CNV) AMD AMD [1] (anti-angiogenic agents) (argon photocoagulation) photodynamic therapy, PDT transpupillary thermotherapy, TTT (Phi-motion indocyanine green angiography) pulse-diode laser (radiation therapy) [3] anti-VEGF pegaptanib( Macugen) Verteporfin ( Visudyne) Ranibizumab ( Lucentis) 3 [4] (S01LA05) ATC code S01LA Sensory organs/ Ophthalmologicals / Ocular vascular disorder agents/ Antineovascularisation agents verteporfin (S01LA01) anecortave (S01LA02) pegaptanib 102 CDR07012_ EYLEA 8/25 (S01LA03) ranibizumab (S01LA04)

7 [5] verteporfin ranibizumab [6] ATC S01LA01 Verteporfin ( Visudyne) 1. 2. 3. 2 3 3 4. FAG S01LA03 pegaptanib( Macugen) <= >=50 S01LA04 Ranibizumab ( Lucentis) (1) ( ) (age-related macular degeneration, AMD) (2) (diabetic macular edema, DME) (3) ( ; branch or central retinal vein occlusion; BRVO CRVO) 1. 2. 3. ~ 4. (1) 50 ( ) (AMD) (101/5/1) I. 3 2 II. FAG (fluorescein angiography) OCT (optical coherence tomography) polypoidal choroidal 102 CDR07012_ EYLEA 9/25 vasculopathy, PCV ICG (indocyanone green angiography) III.

8 I. ii. AMD advanced geographic atrophy iii. (PCV) iv. (angioid streaks) AMD fovea choroidal neovascularization CNV (101/5/1) (2) (diabetic macular edema, DME) ( ) CADTH/pCODR PBAC NICE Cochrane/ Embase PBAC NICE CADTH/pCODR 2013 8 15 SMC/Cochrane/ Pubmed/ Embase 102 CDR07012_ EYLEA 10/25 ( ) PBAC [7] PBAC 2012 3 aflibercept ( EYLEA , solution for intravitreal injection, 40 mg per mL) PBAC ranibizumab ranibizumab cost-minimisation aflibercept 2 mg injection (AFT 2Q8) ranibizumab mg injection (R ) aflibercept ( EYLEA ) (fluorescein angiography) (AMD) (subfoveal choroidal neovascularization, CNV)

9 Optical coherence tomography OCT red free photography PBAC 2012 3 8 ranibizumab ranibizumab aflibercept ranibizumab mg Phase III (VIEW-1 VIEW-2) aflibercept 2 mg injection(AFT 2Q8) ranibizumab mg injection(R ) 52 VIEW-1 VIEW-2 / Phase 3 non- inferiority trials of two years 2,419 patients with active subfoveal, choroidal neovascularization (CNV) lesions (or juxtafoveal lesions with leakage affecting the fovea) comparing ranibizumab mg every month (R ) with three different treatment options of aflibercept ; mg every month The primary end point was noninferiority (margin of 10%) of the aflibercept regimens to ranibizumab in the proportion of patients maintaining vision at week 52 (losing <15 letters on Early Treatment All aflibercept groups were noninferior and clinically equivalent to monthly ranibizumab for the primary end point (the 2q4, , and 2q8 regimens were , , and , respectively, for VIEW 1, and , , and , respectively, for VIEW 2, whereas monthly ranibizumab was in both studies).)

10 The results of vision maintenance comparing aflibercept to ranibizumab across the direct 102 CDR07012_ EYLEA 11/25 secondary to AMD. (AFT ), 2 mg every month (AFT 2Q4) or 2 mg every second month (AFT 2Q8), following three initial monthly injections. Diabetic Retinopathy Study [ETDRS] chart). Other key end points included change in best-corrected visual acuity (BCVA) and anatomic measures. randomised trials showed that both ranibizumab and aflibercept resulted in a high proportion of subjects who maintained vision at week 52. The differences between aflibercept (AFT 2Q8) and ranibizumab (R ) were not statistically significant. The specified non-inferiority criteria was met in all aflibercept treatment arms in the per protocol analysis. The incidence of severe ocular treatment emergent adverse events (TEAEs) in VIEW 1 between R and AFT 2Q8 was significantly lower for AFT 2Q8. However the absolute difference was small and not replicated in VIEW 2.