lampalizumab (RG7417) / Roche - LARVOL DELTA

Oral Antioxidant and Lutein Supplements are not Associated with Geographic Atrophy Progression in Age-related Macular Degeneration (ARVO 2025) - P3 | "Purpose To investigate the effect of Age-Related Eye Disease Study (AREDS) vitamins or other antioxidants and lutein supplements on geographic atrophy (GA) progression in the Lampalizumab Chroma and Spectri clinical trials...Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details."

Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

Reading Performance in Geographic Atrophy: Comparison of Different Reading Speed Measures for Capturing Longitudinal Changes. (PubMed, Ophthalmol Sci) - P3 | "Analysis of data from Chroma (NCT02247479) and Spectri (NCT02247531), 2 identically designed, phase III, double-masked, randomized controlled clinical trials for lampalizumab...All reading speed measures also showed an expected progressive decline over time, but they only showed a weak correlation with GA growth. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article."

Clinical • Journal • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

Deep Learning Approaches to Predict Geographic Atrophy Progression Using Three-Dimensional OCT Imaging. (PubMed, Transl Vis Sci Technol) - P=N/A, P3 | "The study used OCT volumes of GA patients/eyes from the lampalizumab clinical trials (NCT02247479, NCT02247531, NCT02479386); 1219 and 442 study eyes for model development and holdout performance evaluation, respectively...EZ and RPE layers appear to contain the majority of information related to the prediction. Our study provides important insights on the utility of 3D OCT images for GA disease progression predictions."

Journal • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

Visual Loss in Geographic Atrophy: Learnings From the Lampalizumab Trials. (PubMed, Ophthalmology) - P=N/A, P3 | "BCVA and GA area at baseline did not correlate with BCVA loss, but faster GA growth rates appeared to be associated with faster BCVA loss. GA foveal involvement and focality correlated with the rate of BCVA loss with subfoveal lesions at high risk of vision loss over time, especially when the GA lesion was unifocal."

Journal • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

Complement Inhibitors for Geographic Atrophy in Age-Related Macular Degeneration-A Systematic Review. (PubMed, J Pers Med) - "Complement inhibitors may represent a useful therapy for GA in AMD, but a personalized approach to patient selection is necessary to optimize the outcomes."

Journal • Review • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

Intraocular Pressure Outcomes After Lampalizumab Injections in Patients With Geographic Atrophy. (PubMed, JAMA Ophthalmol) - P3 | "These results may be valuable in the design of future therapeutic trials considering this volume for injections particularly as more recently approved agents use volumes of 0.07 to 0.1 mL. ClinicalTrials.gov Identifiers: NCT02247479 and NCT02247531."

Journal • Age-related Macular Degeneration • Cardiovascular • Dry Age-related Macular Degeneration • Glaucoma • Macular Degeneration • Ophthalmology • Retinal Disorders

Machine learning to predict GA growth rate via clinical and derived autofluorescence imaging features (ARVO 2024) - P=N/A, P3 | " This retrospective analysis used macula-centered 30° FAF images (study eye/baseline visit/all treatment arms) from 1281 bilateral GA patients enrolled in lampalizumab Ph3 trials (NCT02247479; NCT02247531) and an observational study (NCT02479386)... To our knowledge, this work achieves the highest published mean CV r2 for predicting GA growth rate via FAF feature-based modeling. The modeling strategy with the highest r2 suggests complementary information provided by separate imaging feature sets. Further work is needed to sculpt the model to robustly identify the most important features, and we aim to understand how clinical and imaging features contribute to GA growth rate prediction.1 Spaide T et al."

Clinical • Machine learning • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Ophthalmology

Investigational drugs inhibiting complement for the treatment of geographic atrophy. (PubMed, Expert Opin Investig Drugs) - "FDA approval of intravitreal pegcetacoplan and avacincaptad pegol marks significant progress in the landscape of GA treatment. However, variable results from trials underscore the complex nature of GA and the importance of patient selection. Complement inhibition holds promise, but ongoing research is vital to refine treatment strategies and offer improved outcomes for GA patients."

Journal • Review • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

Macular Sensitivity Endpoints in Geographic Atrophy: Exploratory Analysis of Chroma and Spectri Clinical Trials. (PubMed, Ophthalmol Sci) - P3 | "Patients were randomized 2:1:2:1 to receive through 96 weeks intravitreal lampalizumab 10 mg every 4 weeks (LQ4W), every 6 weeks (LQ6W), or corresponding sham procedures...Although perilesional, responding, and mean macular sensitivity had weak correlation with GA lesion area, the number of absolute scotomatous points may provide additional information on the anatomic/functional correlation. Proprietary or commercial disclosure may be found after the references."

Clinical • Journal • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Complement inhibitors for age-related macular degeneration. (PubMed, Cochrane Database Syst Rev) - "Despite confirmation of the negative findings of intravitreal lampalizumab across all endpoints, local complement inhibition with intravitreal pegcetacoplan meaningfully reduces GA lesion growth relative to sham at one year. Inhibition of complement C5 with intravitreal avacincaptad pegol is also an emerging therapy with probable benefits on anatomical endpoints in the extrafoveal or juxtafoveal GA population. However, there is currently no evidence that complement inhibition with any agent improves functional endpoints in advanced AMD; further results from the phase 3 studies of pegcetacoplan and avacincaptad pegol are eagerly awaited. Progression to MNV or exudative AMD is a possible emergent adverse event of complement inhibition, requiring careful consideration should these agents be used clinically. Intravitreal administration of complement inhibitors is probably associated with a small risk of endophthalmitis, which may be higher than that of other intravitreal..."

Journal • Review • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ocular Infections • Ocular Inflammation • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

The Role of the Complement Pathway in Clinical Progression of Geographic Atrophy: Analysis of the Phase III Chroma and Spectri Trials. (PubMed, Ophthalmol Sci) - "Aqueous humor (AH) samples collected at baseline and week 24 visits from 81 patients with bilateral GA across all 3 treatment groups (intravitreal lampalizumab 10 mg every 6 weeks, every 4 weeks, or corresponding sham procedures) were tested, along with patient-matched plasma samples collected at baseline...This suggests that local complement activation as measured in AH does not appear to be related to GA lesion progression. Proprietary or commercial disclosure may be found after the references."

Journal • P3 data • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • CFB

Alternative Complement Pathway Inhibition by Lampalizumab: Analysis of Data From Chroma and Spectri Phase III Clinical Trials. (PubMed, Ophthalmol Sci) - "Lampalizumab inhibited the alternative complement pathway in the eyes of patients with GA; however, this did not translate into a measurable reduction in either classical or total complement activity, based on absence of changes in C4 and C3 processing, respectively. Proprietary or commercial disclosure may be found after the references."

Journal • P3 data • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • CFB

Visual function loss in geographic atrophy: learnings from lampalizumab trial data (ARVO 2023) - P=N/A, P3 | "Also, the diseased areas that grew faster were linked to faster sight loss. This information could be useful for doctors to predict how quickly a patient’s eyesight may get worse, which may help when deciding on suitable treatment."

Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

Predicting geographic atrophy growth rate with clinical and derived imaging features (ARVO 2023) - P=N/A, P3 | "Methods This study used FAF images (study eye, baseline visit, all treatment arms) from 1281 patients with bilateral GA enrolled in lampalizumab phase 3 trials (NCT02247479/NCT02247531), and an observational study (NCT02479386)...Our study shows that both the eye images and other features of the patients’ disease are useful to predict the rate of diseased region expansion. This could be valuable information when designing future clinical trials."

Clinical • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

Deep learning to predict future region of growth of geographic atrophy from fundus autofluorescence images (ARVO 2023) - P=N/A, P3 | "Methods A retrospective analysis was performed on study eyes of patients enrolled in lampalizumab trials (NCT02247479, NCT02247531, NCT02479386)...We found that our models could predict the future expansion of GA areas in images with good accuracy. This novel technology could help identify patients at higher risk of worsening GA and help researchers/healthcare providers make more informed decisions regarding patient management."

Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

Visual Function Loss in Geographic Atrophy (GA): Learnings from Lampalizumab Trial Data (Macula 2023) - P=N/A, P3 | "Over three-quarters of eyes with GA will have lost 5 letters of BCVA within 2 years. Baseline factors except lesion focality did not impact on time-to-BCVA loss. GA lesion growth rate analysis showed that more rapid rate of BCVA loss is seen with higher growth rate as compared with lower."

Age-related Macular Degeneration • Dry Age-related Macular Degeneration

Deep Learning to Predict Geographic Atrophy Area and Growth Rate from Multi-modal Imaging (90 characters; max 135 characters). (PubMed, Ophthalmol Retina) - P=N/A, P2, P3 | "We show the feasibility of using baseline FAF images and/or OCT volumes to predict individual GA area and growth rates using a multi-task deep learning approach. The deep learning- based growth rate predictions could be used for covariate adjustment to increase power of clinical trials."

Journal • Age-related Macular Degeneration • Dry Age-related Macular Degeneration

Novel approach to antiangiogenic factors in age-related macular degeneration therapy. (PubMed, Cent Eur J Immunol) - "Among the directions in dry AMD treatment, the most promising are complement cascade inhibitors and complement cascade targeted gene therapy. In the article we outline the main directions in up-to-date experimental and practical approaches to wet and dry AMD therapy with the emphasis on antiangiogenic factors and gene therapy focused on the inhibition of pathological angiogenesis."

Journal • Review • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Gene Therapies • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Development and validation of prognostic models to increase power of clinical trials for geographic atrophy (GA) (ARVO 2022) - P=N/A, P2, P3 | " This study was performed using data from patients in the lampalizumab program... These findings suggest that the FAF-based imaging model, using a single image at baseline, is robust and shows a higher prognostic performance than models with simple features derived at baseline and during a run-in phase. These results suggest that the imaging models can significantly improve trial power and decision making."

Clinical • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Ophthalmology

Already seen [Google Translation] (Retina Today) - "When Retina Today launched 15 years ago, the anti-VEGF era was in its infancy, with the first intraocular agent, pegaptanib...gaining approval just 2 years prior...Everyone who was practicing at the time will never forget the excitement-and relief-we felt to finally have access to approved therapies that made a real difference for our patients with macular degeneration."

Media quote

An Update on Investigational Agents for the Treatment of Geographic Atrophy (Ophthalmology Management) - "Age-related macular degeneration (AMD) is the leading cause of blindness among individuals 50 years and older in many countries including the United States....GA is a devasting disease process, exerting a tremendous toll on afflicted patients independence and quality of life. Genetic and immunohistochemical research has strongly implicated the complement cascade in the pathophysiology of GA, and multiple pharmacotherapies targeting this cascade are in human clinical trials. These therapeutics hold promise for a clinically effective therapy to emerge for GA patients in the future."

Online posting

[VIRTUAL] Multi-modal Geographic Atrophy Lesion Growth Rate Prediction using Deep Learning (ARVO 2021) - " This study was performed retrospectively on study eyes of patients with bilateral GA enrolled in the lampalizumab clinical trials... These findings show the feasibility of using baseline FAF and/or OCT images to predict individual GA growth rate with a multi-task deep learning approach and that a multi-modal approach could improve performance. This work can potentially be useful for clinical trial adjustment, stratification and/or enrichment. Meanwhile, further validation in additional datasets is needed to confirm robust performance."

Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Ophthalmology

Late-Stage Failures of Monoclonal Antibody Drugs: A Retrospective Case Study Analysis. (PubMed, Pharmacology) - "By learning from previous mistakes and adhering to the principles and recommendations provided, it is possible to avoid these common pitfalls, increasing the likelihood of success in phase III clinical trials, and thus securing regulatory approval."

Journal • Retrospective data • Review

[VIRTUAL] Deep learning approach to predict geographic atrophy growth rate from fundus autofluorescence images (EURETINA 2020) - P3 | "Setting: A retrospective analysis was performed using FAF images (study eye, baseline visit, all treatment arms) of patients (n = 640) with bilateral GA enrolled in the negative lampalizumab phase 3 trial, SPECTRI (NCT02247531)... These findings suggest that CNNs can be used to predict GA growth rate from baseline FAF images. The next step is to improve the CNN performance by combining with other imaging modalities (e.g., infra-red and optical coherence tomography) and/or relevant clinical variables."

Age-related Macular Degeneration • Complement-mediated Rare Disorders • Dry Age-related Macular Degeneration

Roche starts trials for vision loss condition drug in Scotland (PBR) - "Roche has started enrolling patients into phase III trials of lampalizumab in Scotland to treat geographic atrophy (GA), an advanced form of age-related macular degeneration (AMD) that leads to a progressive loss of vision."

Enrollment status • Age-related Macular Degeneration • Complement-mediated Rare Disorders • Ophthalmology