ANALYSIS OF RETINAL FLUID AND VISION OUTCOMES IN THE ARCHWAY PHASE 3 TRIAL OF THE PORT DELIVERY SYSTEM WITH RANIBIZUMAB (PDS) IN PATIENTS WITH NAMD PRESENTED AT EURETINA 2021

Y Tế - Sức Khỏe - Y khoa - Dược - Y dược - Sinh học Analysis of Retinal Fluid and Vision Outcomes in the Archway Phase 3 Trial of the Port Delivery System With Ranibizumab (PDS) in Patients With nAMD Presented at EURETINA 2021 Arshad M. Khanani, MD1; Steven Blotner, MS2; Shamika Gune, MD2; and Merce Morral, MD3 1 Sierra Eye Institute, Reno, NV; 2 Genentech, Inc., South San Francisco, CA; 3 F. Hoffmann-La Roche Ltd., Basel, Switzerland  Financial Disclosures AMK: Consultant, Honoraria: 4DMT, Adverum, Aerpio, Alcon, Allergan, Broadwing Bio, Dutch Ophthalmic Research Center, Gemini, Genentech, Inc., Graybug, Gyroscope, Iveric Bio, Kato, Kodiak, Novartis, Opthea, Oxurion, PolyPhotonix, Recens Medical, Regenxbio; Research Support: Adverum, Alkahest, Allegro, Allergan, Annexon, Gemini, Genentech, Inc., Gyroscope, Iveric Bio, Kodiak, NGM Pharmaceuticals, Novartis, Opthea, Ophthotech, Oxurion, Recens Medical, Regenxbio; Speaker: Allergan, Genentech, Inc., Novartis SB, SG: Employee: Genentech, Inc. MM: Employee: F. Hoffmann-La Roche Ltd.  Study Disclosures PDS is an investigational medicine that is being studied for the treatment of neovascular age-related macular degeneration. Its efficacy and safety profile have not been established and it has not been approved by the health authorities This study includes research conducted on human subjects Institutional Review Board approval was obtained prior to study initiation Funding was provided by Genentech, Inc., a member of the Roche Group, for the study and third-party writing assistance, which was provided by Dionne Turnbull, PhD, of Envision Pharma Group Disclosures 2 The Port Delivery System With Ranibizumab (PDS) Continuous Intravitreal Delivery of a Customised Formulation of Ranibizumab  PDS was non-inferior and equivalent to monthly ranibizumab for BCVA change from baseline at weeks 3640, and remained non-inferiord through 2 refill-exchange intervals at weeks 4448  Observed vision and anatomic results were comparable with monthly ranibizumab through week 72  > 90 of PDS patients did not receive supplemental treatmentc before each refill-exchange procedure  93 of PDS patients preferred the PDS over intravitreal injections at week 40  AEs related to the PDS procedures are well understood, manageable and are continually being analysed to optimise patient outcomes Patients with nAMD responsive to any anti-VEGF treatmenta N = 415b Intravitreal ranibizumab 0.5 mg Q4W n = 167 PDS with ranibizumab 100 mgmL Q24Wc n = 248 Randomised 3:2 Weeks 36 and 40: primary endpoint Week 96: final visit Archway Study Design Archway Results a nAMD in study eye diagnosed within 9 months of screening; ≥ 3 intravitreal injections of any anti-VEGF agent within previous 6 months. b Efficacy- and safety-evaluable population. 418 total patients were enrolled, with 251 and 167 patients randomised to the PDS 100 mgmL Q24W and intravitreal ranibizumab 0.5 mg Q4W arms, respectively; 3 patients in the PDS arm did not receive study treatment and were excluded from the efficacy- and safety-evaluable population. c Supplemental intravitreal ranibizumab 0.5 mg injections were available at the 2 visits preceding each refill-exchange procedure if the following protocol-specified disease activity criteria were met: decrease of ≥ 15 letters from the best-recorded BCVA in the study OR increase of ≥ 150 μm in CST on SD-OCT from the lowest CST measurement in the study OR increase of ≥ 100 μm in CST on SD-OCT from the lowest CST measurement in the study associated with a decrease of ≥ 10 letters from the best-recorded BCVA during the study. d Equivalence not assessed at weeks 44 and 48 per protocol. Archway, NCT03677934. AE, adverse event; BCVA, best-corrected visual acuity; CST, central subfield thickness; nAMD, neovascular age-related macular degeneration; PDS, Port Delivery System with ranibizumab; Q4W, every 4 weeks; Q24W, every 24 weeks; SD-OCT, spectral-domain optical coherence tomography; VEGF, vascular endothelial growth factor. 3  SD-OCT images from the Archway trial were subject to dual-read grading, with the entire macula reviewed for SRF and IRF, graded YESNO  If graded YES for SRFIRF, images were further reviewed for SRFIRF at the centre 1 mm SD-OCT Images From Archway Were Graded for SRFIRF Example images of SRF and IRF in participants from the HARBOR study. ETDRS, Early Treatment Diabetic Retinopathy Study; IRF, intraretinal fluid; SD-OCT, spectral-domain optical coherence tomography; SRF, subretinal fluid. ETDRS Grid SRF IRF 4 Percentage of Study Eyes With SRF andor IRF Was Similar Between Treatment Arms and Over Time IRF, intraretinal fluid; PDS, Port Delivery System with ranibizumab; Q4W, every 4 weeks; Q24W, every 24 weeks; SRF, subretinal fluid. 47.6 42.8 51.2 41.8 50.650.9 46.6 42.9 46.3 48.4 0 20 40 60 80 100 Baseline Week 20 Week 24 Week 28 Week 40 Percentage of Study Eyes With SRF andor IRF PDS 100 mgmL Q24W Intravitreal ranibizumab 0.5 mg Q4W 118 85 104 76 125 70 100 75 120 77n 5 BCVA, best-c...

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Analysis of Retinal Fluid and Vision

Outcomes in the Archway Phase 3 Trial of the Port Delivery System With Ranibizumab (PDS) in Patients With nAMD

Presented at EURETINA 2021

1Sierra Eye Institute, Reno, NV; 2 Genentech, Inc., South San Francisco, CA; 3F Hoffmann-La Roche Ltd., Basel, Switzerland

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 Financial Disclosures

Gemini, Genentech, Inc., Graybug, Gyroscope, Iveric Bio, Kato, Kodiak, Novartis, Opthea, Oxurion, PolyPhotonix, Recens Medical, Regenxbio; Research Support: Adverum, Alkahest, Allegro, Allergan, Annexon, Gemini, Genentech, Inc.,

Gyroscope, Iveric Bio, Kodiak, NGM Pharmaceuticals, Novartis, Opthea, Ophthotech, Oxurion, Recens Medical, Regenxbio; Speaker: Allergan, Genentech, Inc., Novartis

Its efficacy and safety profile have not been established and it has not been approved by the health authorities

which was provided by Dionne Turnbull, PhD, of Envision Pharma Group Disclosures

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The Port Delivery System With Ranibizumab (PDS)

Continuous Intravitreal Delivery of a Customised Formulation of Ranibizumab

2 refill-exchange intervals at weeks 44/48

ranibizumab through week 72

each refill-exchange procedure

are continually being analysed to optimise patient outcomes

Patients with nAMD responsive to

Weeks 36 and 40: primary endpoint

Week 96: final visit

anAMD in study eye diagnosed within 9 months of screening; ≥ 3 intravitreal injections of any anti-VEGF agent within previous 6 months bEfficacy- and safety-evaluable population 418 total patients were enrolled, with 251 and 167 patients randomised to the PDS 100 mg/mL Q24W and intravitreal ranibizumab 0.5 mg Q4W arms, respectively; 3 patients in the PDS arm did not receive study treatment and were excluded from the efficacy- and safety-evaluable population cSupplemental intravitreal ranibizumab 0.5 mg injections were available at the 2 visits preceding each refill-exchange procedure if the following protocol-specified disease activity criteria were met:decrease of ≥ 15 letters from the best-recorded BCVA in the study

OR increase of ≥ 150 µm in CST on SD-OCT from the lowest CST measurement in the study OR increase of ≥ 100 µm in CST on SD-OCT from the lowest CST measurement in the study associated with a decrease of ≥ 10 letters from the best-recorded BCVA during the study dEquivalence not assessed at weeks 44 and 48 per protocol Archway, NCT03677934 3

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 SD-OCT images from the Archway trial were subject to dual-read grading, with the entire macula reviewed for SRF and IRF, graded YES/NO

 If graded YES for SRF/IRF, images were further reviewed for SRF/IRF at the centre 1 mm SD-OCT Images From Archway Were Graded for SRF/IRF

Example images of SRF and IRF in participants from the HARBOR study.

ETDRS, Early Treatment Diabetic Retinopathy Study; IRF, intraretinal fluid; SD-OCT, spectral-domain optical coherence tomography; SRF, subretinal fluid.

ETDRS Grid

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Percentage of Study Eyes With SRF and/or IRF Was Similar Between Treatment Arms and Over Time

IRF, intraretinal fluid; PDS, Port Delivery System with ranibizumab; Q4W, every 4 weeks; Q24W, every 24 weeks; SRF, subretinal fluid.

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BCVA, best-corrected visual acuity; ETDRS, Early Treatment Diabetic Retinopathy Study; IRF, intraretinal fluid; PDS, Port Delivery System with ranibizumab; Q4W, every 4 weeks; Q24W, every 24 weeks; SRF, subretinal fluid.

Vision Outcomes Were Similar Between Treatment Arms Both With and Without SRF and/or IRF

PDS 100 mg/mL Q24W no fluidIntravitreal ranibizumab 0.5 mg Q4W no fluidPDS 100 mg/mL Q24W fluidIntravitreal ranibizumab 0.5 mg Q4W fluid

Treatment Arm/Fluid Status at Week 40

Mean Observed BCVA at Baseline

Intravitreal ranibizumab 0.5 mg Q4W no fluid (n = 81)75.7 (20/32)76.4 (20/32)Intravitreal ranibizumab 0.5 mg Q4W fluid (n = 77)75.3 (20/32)75.9 (20/32)

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IRF, intraretinal fluid; PDS, Port Delivery System with ranibizumab; Q4W, every 4 weeks; Q24W, every 24 weeks; SRF, subretinal fluid.

Fluid Dynamics in the Centre 1 mm Were Similar Between Treatment Arms

Relatively Few Patients Had Fluid Presence in the Centre 1 mm

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BCVA, best-corrected visual acuity; ETDRS, Early Treatment Diabetic Retinopathy Study; PDS, Port Delivery System with ranibizumab; Q4W, every 4 weeks; Q24W, every 24 weeks;SRF, subretinal fluid.

Vision Outcomes Were Similar Between Treatment Arms Both With and Without SRF in the Centre 1 mm

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BCVA, best-corrected visual acuity; ETDRS, Early Treatment Diabetic Retinopathy Study; IRF, intraretinal fluid; PDS, Port Delivery System with ranibizumab; Q4W, every 4 weeks;

Intravitreal ranibizumab 0.5 mg Q4W no fluid (n = 147)75.7 (20/32)76.7 (20/32)

Intravitreal ranibizumab 0.5 mg Q4W fluid (n = 11) 72.5 (20/40)69.0 (20/40)

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 In Archway, incidence of retinal fluid (SRF and/or IRF) was generally similar in the PDS Q24W and monthly ranibizumab treatment arms and remained consistent over time

 Vision outcomes on study were comparable, regardless of the overall presence or absence of SRF and/or IRF in either treatment arm

 The presence of IRF in the centre 1 mm was associated with worse vision outcomes, consistent with other trials

 Continuous delivery of ranibizumab with PDS Q24W maintained vision outcomes, regardless of the overall presence or absence of retinal fluid

IRF, intraretinal fluid; PDS, Port Delivery System with ranibizumab; Q24W, every 24 weeks; SRF, subretinal fluid. 10