BA9101 (aflibercept biosimilar) / Luye Group, Ocumension Therap - LARVOL DELTA

Phase IB study of ziv-aflibercept plus pembrolizumab in patients with advanced solid tumors. (PubMed, J Immunother Cancer) - P1 | "The combination of ziv-aflibercept and pembrolizumab demonstrated an acceptable safety profile with antitumor activity in solid tumors. The combination is currently being studied in sarcoma and anti-PD-1-resistant melanoma."

IO biomarker • Journal • P1 data • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Hypertension • Immune Modulation • Inflammation • Lung Cancer • Melanoma • Mesothelioma • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Renal Disease • Sarcoma • Solid Tumor • CD40LG • CD8 • PD-L1

In vitro and in ovo experimental study of two anti-VEGF agents used in ophthalmology. (PubMed, Rom J Morphol Embryol) - "Treatment with anti-VEGF drugs like Bevacizumab (Avastin®) and Aflibercept has proven optimistic results in various malignant diseases. In both cases, the only notable change was the appearance of a slight vascular coagulation. The viability of the embryos after application was good, they survived more than 24 hours after testing the compounds on the CAM."

Journal • Preclinical • Melanoma • Oncology • Ophthalmology • Solid Tumor

Retrospective Analysis of the Pharmaco-Utilization of VEGF Inhibitors and Health Care Costs among Patients with Wet Age-Related Macular Degeneration and Other Ocular Diseases in Italy. (PubMed, Int J Environ Res Public Health) - "Across January 2010-December 2017, patients aged ≥50 years with a prescription of intravitreal anti-VEGFs were included as "wAMD" patients [by wAMD hospitalization or intravitreal injections] or as "other ocular diseases" patients [by hospitalization for other ocular disorders or intravitreal injections, with concomitant diabetes diagnosis or dexamethasone treatment]...Overall, 2646 patients were enclosed; 85.9% were treated with Ranibizumab, 13.5% with Aflibercept, and 0.6% with Pegaptanib. During the follow-up, the mean/annual anti-VEGF prescription [3.3 (first-year)-0.5 (third-year)] and the total cost [7196.83 € (first-year)-5162.68 € (third-year)] decreased. This observational study highlighted a decline in anti-VEGF prescriptions over time in both cohorts, suggesting a trend of under-treatment that could worsen the patients' clinical outcomes and increase health care resource consumption."

HEOR • Journal • Retrospective data • Age-related Macular Degeneration • Diabetes • Macular Degeneration • Metabolic Disorders • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Brolucizumab for the treatment of diabetic macular edema. (PubMed, Curr Opin Ophthalmol) - "Results from recent phase III trials showing the efficacy and safety of brolucizumab presents an additional therapeutic option in the DME treatment landscape. It can reduce treatment burden in DME with increased inter-treatment intervals while conferring efficacy in both functional and anatomical outcomes. Caution should be taken regarding the risks of intraocular inflammation, retinal vasculitis, and retinal vascular occlusion."

Journal • Diabetic Macular Edema • Immunology • Inflammation • Ocular Inflammation • Ophthalmology • Retinal Vein Occlusion • Vasculitis

Final Outcomes from the Randomized RECOVERY Trial of Alfibercept for Retinal Nonperfusion in Proliferative Diabetic Retinopathy. (PubMed, Ophthalmol Retina) - "Through year 2 of RECOVERY, both treatment arms experienced significant increases in RNP. Despite expansion of RNP area in nearly all subjects, 82% demonstrated an improvement in DRSS levels from baseline with no subject experiencing worsening in DRSS."

Clinical • Journal • Diabetic Retinopathy • Retinal Disorders

A Comparison of Folinic Acid, Fluorouracil and Irinotecan (FOLFIRI) plus Bevacizumab and FOLFIRI plus Aflibercept as Second-line Treatment for Metastatic Colorectal Cancer. (PubMed, Clin Oncol (R Coll Radiol)) - "FOLFIRI plus bevacizumab and FOLFIRI plus aflibercept had similar anti-tumour activities and toxicity profiles when used as second-line therapy in mCRC patients. Based on these data, both aflibercept and bevacizumab are suitable anti-angiogenic agents when used in combination with FOLFIRI for mCRC."

Journal • Colorectal Cancer • Gastrointestinal Cancer • Hypertension • Oncology • Solid Tumor

Short-Term Efficacy in Polypoidal Choroidal Vasculopathy Patients Treated With Intravitreal Aflibercept or Conbercept. (PubMed, Front Med (Lausanne)) - "A relatively high proportion of polyp regression was observed in the IVA group (63%) compared with the IVC group (55%) via OCTA. Visual and anatomic outcomes were significantly improved in both IVA and IVC groups, but the results suggest a potentially superior short-term response in the IVA group."

Journal • Age-related Macular Degeneration

Long-term outcomes of anti-VEGF treatment of macular oedema due to retinal vein occlusions. (PubMed, Eur J Ophthalmol) - "the results demonstrate that anti-VEGF treatment of RVO benefits vision for up to 5 years. Our findings are the first to suggest that compared to ranibizumab, fewer aflibercept injections may be required over five years follow up. Prospective randomised trials are needed to confirm this, alongside further attention to OCT scan features and the effect of patient demographics on treatment outcomes."

Journal • Macular Edema • Ophthalmology • Retinal Vein Occlusion

Efficacy and safety of aflibercept plus chemotherapy in metastatic colorectal cancer: A systematic review and PRISMA-Compliant single-arm Meta-Analysis of noncomparative clinical studies and randomized controlled trials. (PubMed, J Clin Pharm Ther) - "Analysis of data from randomized controlled trials(RCT) and single-arm clinical trials confirmed the good efficacy of aflibercept plus chemotherapy in mCRC, while the safety of the treatment is concerning."

Journal • Retrospective data • Review • Colorectal Cancer • Gastrointestinal Cancer • Hematological Disorders • Hypertension • Mucositis • Neutropenia • Oncology • Renal Disease • Solid Tumor • Stomatitis

Effect Modification by Indication to the Risks of Major Thromboembolic Adverse Events in Patients Receiving Intravitreal Anti-Vascular Endothelial Growth Factor Treatment: A Population-Based Retrospective Cohort Study. (PubMed, BioDrugs) - "Patients treated with aflibercept or ranibizumab for different indications may be associated with varying risk of TAEs. The findings provide evidence to support treatment selection, taking indications and TAE risk into consideration."

Adverse events • Journal • Retrospective data • Age-related Macular Degeneration • Cardiovascular • Coronary Artery Disease • Diabetic Macular Edema • Heart Failure • Hematological Disorders • Ischemic stroke • Macular Degeneration • Ophthalmology • Pulmonary Embolism • Respiratory Diseases • Retinal Disorders • Venous Thromboembolism • Wet Age-related Macular Degeneration

Outcomes after switching eyes that were stable on aflibercept to ranibizumab versus continuing aflibercept in neovascular age-related macular degeneration. (PubMed, Graefes Arch Clin Exp Ophthalmol) - "nAMD eyes that were stable or improving on aflibercept but were switched to ranibizumab worsened, while those in a comparable group maintained on aflibercept remained fairly stable, suggesting a potential efficacy difference between the two drugs."

Journal • Age-related Macular Degeneration • Immunology • Inflammation • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Switching from aflibercept to brolucizumab for the treatment of refractory neovascular age-related macular degeneration. (PubMed, Jpn J Ophthalmol) - "Switching to brolucizumab in eyes refractory to aflibercept conferred favorable outcomes in controlling exudative changes. However, IOI and the regulation of the treatment interval to at least 8 weeks during the maintenance phase disrupted the continuation of brolucizumab treatment."

Journal • Age-related Macular Degeneration • Immunology • Inflammation • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

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

Anti-VEGF Drugs Dynamics: Relevance for Clinical Practice. (PubMed, Pharmaceutics) - "Fixed q8 ranibizumab, q8 bevacizumab, q12 aflibercept, or q10 brolucizumab regimens may produce adequate intraocular VEGF inhibition."

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

Epimacular brachytherapy for previously treated neovascular age-related macular degeneration: month 36 results of the MERLOT randomised controlled trial. (PubMed, Br J Ophthalmol) - P4 | "EMB does not reduce the number of anti-vascular endothelial growth factor (VEGF) injections, either within or outside of a trial setting, and is associated with worse BCVA than anti-VEGF monotherapy."

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

Electrophysiological evaluation and 18-month follow-up of two regimens with aflibercept for neovascular age-related macular degeneration. (PubMed, Doc Ophthalmol) - "After 18 months, both treatments arms have received a similar number of injections at comparable intervals. Electrophysiological evaluation shows no signs of toxicity concerning cone function. But ffERGs for the combined and isolated rod response have declined, possibly reflecting either toxic effects of the drug to rods or the natural course of the disease itself."

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

VEGF-Trap Modulates Retinal Inflammation in the Murine Oxygen-Induced Retinopathy (OIR) Model. (PubMed, Biomedicines) - "VEGF-Trap (Aflibercept, AFL), a recombinant decoy receptor recognizing ligands of both VEGFR-1 and -2, was recently reported to be highly efficient in improving visual acuity and preserving retinal anatomy in individuals affected by diabetic macular edema...We show that AFL administration during the hypoxic period of OIR leads to an increased number of ramified Iba1 microglial cells/macrophages while subsequently limiting the accumulation of these cells in particular retinal layers. Our results suggest that, beyond its well-documented beneficial effects on microvascular regeneration, AFL might exert important modulatory effects on post-ischemic retinal inflammation."

Journal • Preclinical • Diabetic Macular Edema • Diabetic Retinopathy • Immunology • Inflammation • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinopathy of Prematurity • FLT1 • VEGFA

Mid-Term Impact of Anti-Vascular Endothelial Growth Factor Agents on Intraocular Pressure. (PubMed, J Clin Med) - "These were treatment-naïve patients who had received at least three injections of the same treatment (aflibercept, bevacizumab, or ranibizumab) in one eye only, and had IOP measurements before and after the injections. Ranibizumab was associated with a higher rate of increase in clinically significant IOP at 6 months (p = 0.03). Our study confirms that anti-VEGF injections constitute a relatively safe treatment regarding their impact on IOP."

Journal

The Effectiveness of Brolucizumab and Aflibercept in Patients with Neovascular Age-Related Macular Degeneration. (PubMed, Int J Environ Res Public Health) - "The analysis consisted of 40 patients diagnosed with neovascular age-related macular degeneration, with 20 patients receiving aflibercept (Eylea, Bayer) at a dose of 2 mg/50 µL into the vitreous chamber at the following intervals-3 doses, 4 weeks apart, followed by a fourth dose after 8 weeks. We found a higher effectiveness of brolucizumab therapy compared to aflibercept in patients with nAMD during an observations period lasting 20 weeks. Our observations are significant, although they require further research."

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

Competition law and pricing among biologic drugs: the case of VEGF therapy for retinal diseases. (PubMed, J Law Biosci) - "Currently, treatment options include three originator biologics with approvals for neovascular AMD (aflibercept, ranibizumab, and brolucizumab-dbll) and one biologic that is commonly used off-label for the condition (bevacizumab). We propose mechanisms for anticipating and facilitating the market introduction of biosimilars, as well as changes to the pricing model in Medicare that can promote use of cost-effective therapies. Reforms such as empowering Medicare to negotiate drug prices may help ensure that introduction of new biologics and biosimilars for AMD will lower spending and increase patient access."

Journal • Pricing • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

The sterility, stability and efficacy of repackaged ziv-aflibercept for intravitreal administration. (PubMed, Sci Rep) - "However, the concentration of ziv-aflibercept decreased less than the minimum expected concentration of 8 ng/mL after 60 days at 4 °C and after 30 days at 25.8 °C. The repackaged anti-VEGF drug ziv-aflibercept does not lose stability or efficacy and remains uncontaminated if prepared under sterile conditions and stored at 4 °C for up to 60 days or stored at 25.8 °C for up to 30 days."

Journal

Update on Management of Non-proliferative Diabetic Retinopathy without Diabetic Macular Edema; Is There a Paradigm Shift? (PubMed, J Ophthalmic Vis Res) - "In addition, recent randomized trials (PANORAMA and Protocol W) have revealed that early intervention with intravitreal aflibercept in eyes with moderately severe to severe NPDR is associated with significant improvement in DRSS and reduced vision-threatening complications of DR...The cost-benefit ratio is also a challenge. Herein, we look at different aspects of early anti-VEGF application and discuss its pros and cons in the process of treating NPDR."

Journal • Review • Diabetic Macular Edema • Diabetic Retinopathy • Ophthalmology • Retinal Disorders

Novel volumetric imaging biomarkers for assessing disease activity in eyes with PCV. (PubMed, Sci Rep) - "In this prospective study we enrolled participants with treatment-naïve PCV who followed a treat-and-extend protocol using intravitreal aflibercept (IVA) monotherapy...PED-related volumetric parameters have an additional predictive value to traditional biomarkers of disease activity in eyes with PCV undergoing anti-VEGF monotherapy. With increasingly precise quantification, PEDs can be a crucial biomarker in addition to traditional parameters and may aid in retreatment decisions."

Biomarker • Journal • Diabetic Retinopathy • Retinal Disorders

Comparison of Fluorescein Angiography Findings in Stage 3 Retinopathy of Prematurity in Zone II Treated With or Without Anti-VEGF. (PubMed, Eur J Ophthalmol) - "Vascular abnormalities in the peripheral retina are likely due to the ROP itself. Although these abnormalities were detected by FA imaging in both treated and untreated infants with ROP, they were significantly less frequent in patients treated with anti-VEGF, indicating that anti-VEGF treatments have a partially positive effect on the retinal vascularization process."

Journal • Retinal Disorders • Retinopathy of Prematurity

"Yes! I recently saw this with intravitreal Aflibercept" (@DerekSLarson)