nesvacumab/aflibercept intravitreal (REGN 910-3) / Regeneron, Bayer - LARVOL DELTA

Intravitreal Nesvacumab (Anti-Angiopoietin-2) Plus Aflibercept in Neovascular AMD: Phase 2 ONYX Randomized Trial. (PubMed, J Vitreoretin Dis) - "Serious ocular adverse events were infrequent and comparable across groups. In nAMD, nesvacumab + aflibercept showed no additional BCVA or CST benefit over IAI monotherapy."

Journal • P2 data • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Longitudinal Quantitative Ultra-Widefield Fluorescein Angiography Dynamics in the RUBY DME Study. (PubMed, Ophthalmol Retina) - "Assessment of UWFA parameters demonstrates a significant improvement in panretinal leakage index, leakage area, and MA burden in eyes treated with IAI with or without nesvacumab. A numerical reduction in panretinal ischemic index and area was also noted. The analysis also shows the critical association of leakage with visual and OCT features. This highlights the potential role of UWFA in disease burden assessment, with leakage parameters serving as a primary endpoint."

Journal • Cardiovascular • Diabetic Macular Edema • Ophthalmology

Intravitreal Nesvacumab (Anti-Angiopoietin 2) Plus Aflibercept in Diabetic Macular Edema: The Phase 2 RUBY Randomized Trial. (PubMed, Retina) - "Nesvacumab+aflibercept demonstrated no additional visual benefit over IAI. Anatomic improvements with HD combo may warrant further investigation."

Journal • P2 data • Diabetic Macular Edema • Ophthalmology

The emerging role of the angiopoietin-Tie pathway as therapeutic target for treating retinal diseases. (PubMed, Expert Opin Ther Targets) - "We analyzed the novel, emerging drugs (ARP- 1536, the coformulation of aflibercept and nesvacumab, AXT107 and AKB-9778) that target the Ang/Tie pathway. Further clinical trials are necessary to define the role of agents targeting Ang/Tie in future clinical practice. Among the investigational drugs targeting the Ang/Tie pathway, faricimab has shown promising results in phase II/III trials and in the near future may represent a viable treatment option for the management of exudative macular diseases."

Journal • Age-related Macular Degeneration • Diabetic Macular Edema • Macular Degeneration • Ophthalmology • Retinal Disorders • Retinal Vein Occlusion • Wet Age-related Macular Degeneration

Assessment of Ellipsoid Integrity and Volumetric Fluid Features in the RUBY DME Study Using Machine Learning–Enhanced OCT Analysis (AAO 2021) - "Methods This was a post hoc analysis of the Phase 2 RUBY clinical trial that evaluated combined intravitreal nesvacumab+aflibercept and intravitreal aflibercept (IAI)...Conclusion Longitudinal assessment of fluid dynamics and EZ integrity demonstrates significant improvement in the RUBY trial. These parameters correlate with functional outcomes."

Diabetic Macular Edema • Ophthalmology

RUBY: Anti-vasculaR Endothelial Growth Factor plUs Anti-angiopoietin 2 in Fixed comBination therapY: Evaluation for the Treatment of Diabetic Macular Edema (clinicaltrials.gov) - P2; N=304; Completed; Sponsor: Regeneron Pharmaceuticals; Active, not recruiting ➔ Completed

Trial completion • Biosimilar • Diabetes • Diabetic Macular Edema • Metabolic Disorders • Ophthalmology

ONYX: Anti-angiOpoeitin 2 Plus Anti-vascular eNdothelial Growth Factor as a therapY for Neovascular Age Related Macular Degeneration: Evaluation of a fiXed Combination Intravitreal Injection (clinicaltrials.gov) - P2; N=360; Recruiting; Sponsor: Regeneron Pharmaceuticals

New P2 trial • Biosimilar • Complement-mediated Rare Disorders • Gene Therapies

Regeneron: The amazon of biotech? (SeekingAlpha) - "...Eylea/nesvacumab combo is in Phase 2, with results expected next year. Potentially important is that this Phase 2 program is both in wet AMD and in a diabetic eye disease; this likely reflects REGN's greater expectations for nesvacumab than rinucumab."

Anticipated P2 data • Age-related Macular Degeneration • Ophthalmology

Phase 1 Study of Combination Therapy With Nesvacumab and Aflibercept for Neovascular AMD and Diabetic Macular Edema (AAO 2016) - "Methods This was an open-label, dose-escalating, Phase 1 study of nesvacumab / aflibercept (REGN910-3), a coformulation providing both agents in a single intravitreal injection, and nesvacumab alone in patients with neovascular AMD (n = 10) and DME (n = 10). Visual and anatomic improvements were seen with intravitreal nesvacumab / aflibercept at all dose levels. Conclusion At all evaluated dose levels, combination therapy with nesvacumab / aflibercept did not result in DLT; visual and anatomic benefits were observed."

Clinical • Combination therapy • P1 data • Age-related Macular Degeneration • Biosimilar • Complement-mediated Rare Disorders • Diabetes • Diabetic Macular Edema • Gene Therapies • Ophthalmology

Tie-2/Angiopoietin pathway modulation as a therapeutic strategy for retinal disease. (PubMed, Expert Opin Investig Drugs) - "Areas covered: Faricimab, a bispecific antibody that inhibits VEGF-A and Ang-2, is in phase 3 trials for nAMD and DME. Nesvacumab is an Ang-2 inhibitor; when coformulated with aflibercept, it failed to show benefit over aflibercept monotherapy in achieving visual gains in phase 2 studies of nAMD and DME. ARP-1536 is an intravitreally administered VE-PTP inhibitor undergoing preclinical studies. AKB-9778 is a subcutaneously administered VE-PTP inhibitor that, when combined with monthly ranibizumab, reduced DME more effectively than ranibizumab monotherapy in a phase 2 study...AXT107, currently in the preclinical phase, promotes conversion of Ang-2 into a Tie-2 agonist and blocks signaling through VEGFR2 and other receptor tyrosine-kinases. Expert Opinion: Tie-2/Angiopoietin pathway modulators show promise to reduce treatment burden and improve visual outcomes in nAMD and DME, with potential to treat cases refractory to current treatment modalities."

Journal • Review