nesvacumab (REGN910) / Regeneron, Sanofi - 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

Angiopoietin inhibitors: A review on targeting tumor angiogenesis. (PubMed, Eur J Pharmacol) - "Drugs studied in the article are selective as well as non-selective inhibitors of angiopoietin 2 like Trebananib (AMG 386), AMG 780, REGN 910, CVX 060, MEDI 3617 and dual inhibitors of angiopoietin 2 and VEGF like Vanucizumab and RG7716. The angiopoietin inhibitors show promising results alone and in combination with VEGF inhibitors in various malignancies."

Journal • Review • Immunology • Inflammation • Oncology

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

Study of Nesvacumab (REGN910/ SAR307746) (clinicaltrials.gov) - P1; N=53; Active, not recruiting; Sponsor: Regeneron Pharmaceuticals; N=72 -> 53

Enrollment change • Biosimilar • Oncology

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

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

Nesvacumab: "No significant differences in mean change in BCVA between combination of nesvacumab+aflibercept vs. IAI monotherapy" (Regeneron Pharmaceuticals) - Angiogenesis Conference 2018: "No significant differences in mean change in CRT between combination of nesvacumab+aflibercept vs. IAI monotherapy"

P2 data • Age-related Macular Degeneration • Ophthalmology

Nesvacumab: "Ocular and systemic safety consistent with IAI monotherapy" (Regeneron Pharmaceuticals) - Angiogenesis Conference 2018

P2 data • Diabetic Macular Edema • Ophthalmology

Nesvacumab: "Results suggest improvement in vision and retinal morphology" (Regeneron Pharmaceuticals) - ASRS 2017

P1 data • Age-related Macular Degeneration • Ophthalmology

Phase 1 first-in-human (FIH) study of nesvacumab (REGN910) a fully human and selective angiopoietin-2 (Ang2) monoclonal antibody (MAb): Results from hepatocellular carcinoma (HCC) cohort (ASCO 2014) - Presentation time: Sunday, Jun 1; 8:00 AM - 11:45 AM; Abstract #2540; P1, N=15; Sponsor: Regeneron Pharmaceuticals; NCT01271972; "No objective responses were observed. Two pts experienced a ≥ 50% decline in AFP (1 pt >90%). Nine of 15 pts achieved best response of SD (median duration 24 wks); 6 pts achieved SD for ≥ 20 wks. Notably, 5 of 8 pts treated at 20 mg/kg achieved best response of SD; median duration of 40 wks."

P1 data • Hepatocellular Cancer • Oncology

A phase I first-in-human study of REGN910 (SAR307746), a fully human and selective angiopoietin-2 (Ang2) monoclonal antibody (MAb), in patients with advanced solid tumor malignancies (ASCO 2013) - Presentation time: Tue, Jun 4, 8:00 AM - 12:00 PM; Abstract #2517; P1, N=37; NCT01271972; Sponsor: Regeneron; "No DLTs were reported, and a MTD was not reached...Across all dose levels, REGN910 pharmacokinetics appeared linear and dose-proportional. The PK profile was characterized by an initial distribution and a single mono-exponential elimination phase"

P1 data • Oncology

A phase 1b study of combined angiogenesis blockade with nesvacumab, a selective monoclonal antibody (MAb) to angiopoietin-2 (Ang2) and ziv-aflibercept in patients with advanced solid malignancies (ASCO 2014) - Presentation time: Friday, May 30; 1:00 PM - 4:00 PM; Abstract #2522; P1, N=30; Sponsor: Regeneron Pharmaceuticals; NCT01688960; "Two pts achieved PR: 1 pt with CRC previously treated with bevacizumab (32+ wk) and 1 pt with OvCa (19 wks);15 patients achieved disease control with median duration of 29 wks; 7 pts experienced SD ≥16 wks. Across all dose levels, the PK and resulting systemic exposures of both N and Z were not affected by co-administration of the 2 agents."

P1 data • Oncology

Innovative therapies for neovascular age-related macular degeneration. (PubMed, Expert Opin Pharmacother) - "Expert opinion: Long-acting anti-VEGF agents have demonstrated promising results in phase 3 studies, and include Brolucizumab, a single-chain antibody fragment, and Abicipar, a designed ankyrin repeat protein (DARPin). Other unique anti-VEGF agents in current trials include Conbercept - a fusion protein of the VEGF receptor domains, KSI-301 - an anti-VEGF antibody biopolymer conjugate, and OPT-302 - an inhibitor of VEGF-C/D. Strategies to activate the Tie-2 receptor, some in combination with VEGF inhibition, are of interest, with recent trials of Faricimab, ARP-1536, and nesvacumab. Topical anti-VEGF ± anti-PDGF agents, such as pazopanib, squalamine lactate, regorafenib, and LHA510 have shown limited efficacy and/or have not been advanced, although PAN-90806 continues to advance with promising initial results. Sustained-release anti-VEGF treatments, to address treatment burden, include the ranibizumab Port Delivery System, GB-102, NT-503, hydrogel depot,..."

Journal

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