New molecules in the treatment of diabetic macular edemaandupdate on screening of diabeticretinopathyPentalfa 6 december 2018Julie Jacob MD, PhDMedische retina UZ Leuven

New molecules in thetreatment of diabeticmacular edema

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%)

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

brolucizumab

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• Targets VEGF-A, small molecule• AMD study, DME trials ongoing

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

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

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

RG7716 = faricimab

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• Ang2 en VEGF are key drivers of angiogenesis• Angiopoietin/Tie2 axis modulates endothelial cell stabilization

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

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

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

KVD001

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• Protease inhibitor• Targets plasma kallikrein, VEGF-independent mediator of DME• Fase 2 study ongoing

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

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

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

AKB-9778

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• Tie2 activator• Aim: prevent development of DME• Self-administered subcutaneously

Update on screening fordiabetic retinopathy

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