new molecules in the treatment of diabetic macular …...new molecules in the treatment of diabetic...
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New molecules in the treatment of diabetic macular edemaandupdate on screening of diabeticretinopathyPentalfa 6 december 2018Julie Jacob MD, PhDMedische retina UZ Leuven
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New molecules in thetreatment of diabeticmacular edema
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Diabetic macular edema• Anti-VEGF A
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Diabetic macular edema• Differences in anti-VEGF agents
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Diabetic macular edema• DRCRnet: different patient populations
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Categorisation of OCT thickness improvement of at least 20% from baseline (n=288) (1 step reduction of logOCT)Early and consistent Early but
inconsistentSlow and variable Non-responder
Improved at the 16-week study visit andwas sustained at the32-week and 1-year study visits
Improved at the 16 week study visit but not at both the 32-week and 1-year study visits
Did not improve at the 16-week studyvisit but did improveat the 32-week and/or 1-year studyvisits
Did not improved at the 16-week, 32-week, or 1-year study visit
N=143 (49,7%) N=43 (14,9%) N=36 (12,5%) N=66 (25,9%)
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Diabetic macular edema• Future treatment of diabetic eye disease
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Next generation anti-VEGF-A drugs
• brolucizumab• abicipar pegol• conbercept
Combination drugs
• RG7716• nesvacumab +
aflibercept• OPT 302• ALG-1001• KVD001
Suprachoroidal corticosteroid
• CLS-TA
Subcutaneous Tie2 activator
• AKB-9778
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brolucizumab
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• Targets VEGF-A, small molecule• AMD study, DME trials ongoing
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brolucizumab
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DARPin (abicipar pegol)
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• Designed ankyrin repeat protein, antibody mimetic products• PALM study fase 2:
o Non inferiority of abicipar pegol every 8 or 12 weeks compared to monthly ranibizumab for functional and anatomical outcomes
o Patients treated with abicipar pegol 2 mg required fewer injections than those treated with ranibizumab over a period of 28 weeks
o Cave: up to 15% of patients developed inflammation!
Hassan TS. A multicenter, double masked phase 2 clinical trial evaluating abicipar pegol for diabeticmacular edema. Paper presented at: AAO 2016
Presentation Pr a Loewenstein – Euretina 2018
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Conbercept: Lumitin
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• Fully humanized fusion protein: VEGF R1 domain 2, VEGF R2 domain 3,4 and Fc of human IgG
• Inhibits VEGF-A, VEGF-B and PlGF• Fase 2 trials show improvement in VA and decreases in RT on
OCT in DME patients• Additional trials in DME are being planned
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Diabetic macular edema• Future treatment of diabetic eye disease
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Next generation anti-VEGF-A drugs
• brolucizumab• abicipar pegol• conbercept
Combination drugs
• RG7716• nesvacumab +
aflibercept• OPT 302• ALG-1001• KVD001
Suprachoroidal corticosteroid
• CLS-TA
Subcutaneous Tie2 activator
• AKB-9778
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RG7716 = faricimab
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• Ang2 en VEGF are key drivers of angiogenesis• Angiopoietin/Tie2 axis modulates endothelial cell stabilization
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RG7716 = faricimab
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RG7716 = faricimab
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Nesvacumab + aflibercept
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• Anti-Ang2 • Anti-VEGF A, B en PlGF
o Coformulationo 1 injectiono Fase 2: no differentiation
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OPT-302 + anti-VEGF-A
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• Anti-VEGF-C and Do Blocks VEGFR2 & 3o Trap molecule: binds and neutralizes activity of VEGF-C and Do Fase 1 and 2 trials evaluating OPT 302 in combination with
aflibercept
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ALG-1001
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• Integrin peptide therapy• Fase 2 DEL MAR study: pt resistant to anti-VEGF A monotherapy responded
best to sequential therapy with anti-VEGF followed by ALG-1001
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KVD001
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• Protease inhibitor• Targets plasma kallikrein, VEGF-independent mediator of DME• Fase 2 study ongoing
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Diabetic macular edema• Future treatment of diabetic eye disease
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Next generation anti-VEGF-A drugs
• brolucizumab• abicipar pegol• conbercept
Combination drugs
• RG7716• nesvacumab +
aflibercept• OPT 302• ALG-1001• KVD001
Suprachoroidal corticosteroid
• CLS-TA
Subcutaneous Tie2 activator
• AKB-9778
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CLS-TA
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• Triamcinolone acetonide into the suprachoroidal space• Fase 1 HULK trial: CLS-TA ± aflibercept: signs of increased efficacy
and durability• Fase 2 TYBEE: CLS-TA+aflibercept vs aflibercept
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Diabetic macular edema• Future treatment of diabetic eye disease
24
Next generation anti-VEGF-A drugs
• brolucizumab• abicipar pegol• conbercept
Combination drugs
• RG7716• nesvacumab +
aflibercept• OPT 302• ALG-1001• KVD001
Suprachoroidal corticosteroid
• CLS-TA
Subcutaneous Tie2 activator
• AKB-9778
![Page 23: New molecules in the treatment of diabetic macular …...New molecules in the treatment of diabetic macular edema and update on screening of diabetic retinopathy Pentalfa 6 december](https://reader034.vdocuments.us/reader034/viewer/2022042310/5ed86f88b7394006ce603144/html5/thumbnails/23.jpg)
AKB-9778
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• Tie2 activator• Aim: prevent development of DME• Self-administered subcutaneously
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Update on screening fordiabetic retinopathy
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Screening for DRP
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• Prevalence of DR is increasing• Repetitive screening is cost-effective but is also costly and strenuous• National screening programs in UK and Singapore• Automated retinal image analysis? (ARIA)
o Sophisticated algorithms utilizing advanced mathematical modelingo 2 systems
• Disease/no disease• Disease severity, need of referral
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Future of DR screening
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TelemedicineBetter imaging technologies
Automatic assessment of fundus photographs
Individualized risk assessment:- Type and duration of diabetes- Presence and grade of retinopathy- Systolic blood pressure- Gender- Blood glucose level (HbA1c)
Multi-technology and customizedDR screening