Impact of Modifying Abicipar Manufacturing Process in Patients with Neovascular Age-Related Macular Degeneration: MAPLE Study Results.

Purpose: To evaluate the impact of modifying the abicipar pegol (abicipar) manufacturing process on the safety and treatment effect of abicipar in patients with neovascular age-related macular degeneration (nAMD).

Methods: A new process for manufacturing abicipar was developed to reduce host cell impurities. In a prospective, Phase 2, multicenter, open-label, 28-week clinical trial, patients (n=123) with active nAMD received intravitreal injections of abicipar 2 mg at baseline (day 1) and weeks 4, 8, 16, and 24.

Effect of Anti-VEGF Therapy on the Disease Progression of Neovascular Age-Related Macular Degeneration: A Systematic Review and Model-Based Meta-Analysis.

Anti-vascular endothelial growth factor (VEGF) therapy is used to slow the disease progression of neovascular age-related macular degeneration. Due to the treatment burden of frequent intravitreal injections, anti-VEGFs are often used on treat and extend protocols rather than the labeled frequency. The current goal of anti-VEGF drug development is to minimize treatment burden by reducing the number of intravitreal injections.

A Mechanistic and Translational Pharmacokinetic-Pharmacodynamic Model of Abicipar Pegol and Vascular Endothelial Growth Factor Inhibition.

Abicipar pegol (abicipar) is a novel DARPin therapeutic and highly potent vascular endothelial growth factor (VEGF) inhibitor intended for the treatment of neovascular age-related macular degeneration (nAMD). Here we develop a translational pharmacokinetic/pharmacodynamic (PK/PD) model for abicipar to guide dosing regimens in the clinic. The model incorporated abicipar-VEGF binding kinetics, VEGF expression levels, and VEGF turnover rates to describe the ocular and systemic PK data collected from the vitreous, aqueous humor (AH), choroid, retina, and serum of rabbits after a 1-mg abicipar intravitreal (IVT) dose.

Intracameral Sustained-Release Bimatoprost Implant Delivers Bimatoprost to Target Tissues with Reduced Drug Exposure to Off-Target Tissues.

Purpose: To explore the ocular distribution of bimatoprost after intracameral administration of a biodegradable sustained-release bimatoprost implant (Bimatoprost SR) versus repeated topical administration of bimatoprost 0.03% ophthalmic solution in dogs. Bimatoprost SR and topical bimatoprost 0.

Lipid-soluble 3-pyridinol antioxidants spare alpha-tocopherol and do not efficiently mediate peroxidation of cholesterol esters in human low-density lipoprotein.

Because alpha-tocopherol (alpha-TOH) mediates the peroxidation of cholesterol-esterified lipids in human low-density lipoprotein (LDL) in vitro and has displayed disappointing results against the onset and development of atherosclerosis, it may not be appropriate for use as a therapeutic in the prevention and/or treatment of the disease. Herein are described the experimental results demonstrating that 3-pyridinols spare alpha-TOH, do not efficiently mediate lipid peroxidation, and protect lipoprotein tryptophan residues in human LDL.

Identification and analysis of products formed from phospholipids in the free radical oxidation of human low density lipoproteins.

Phospholipids reside in the surface layer of LDLs and constitute approximately 20-25% of the particle by weight. We report a study of the primary products generated from the most abundant molecular species of phosphatidylcholines present in LDL during in vitro free radical oxidations. The 13-hydroperoxides of 1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphocholine (PLPC) and 1-stearoyl-2-linoleoyl-sn-glycero-phosphocholine (SLPC) and the 15-hydroperoxides of 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphocholine (PAPC) and 1-stearoyl-2-arachidonoyl-sn-glycero-phosphocholine (SAPC) were found to increase in a time-dependent manner and in significant amounts even in the presence of alpha-tocopherol.

Liquid chromatography coordination ion-spray mass spectrometry (LC-CIS-MS) of docosahexaenoate ester hydroperoxides.

Coordination ion-spray mass spectrometry (CIS-MS) is a useful tool in the detection and identification of complex mixtures of cholesterol ester and phospholipid hydroperoxides. The methyl ester, cholesterol ester, and phospholipid hydroperoxides of docosahexaenoic acid were analyzed by LC-CIS-MS and their elution orders were identified. Their corresponding alcohols were also identified.

Analysis of unsaturated compounds by Ag+ coordination ionspray mass spectrometry: studies of the formation of the Ag+/lipid complex.

Coordination ionspray mass spectrometry (CIS-MS) is a useful tool in the detection and identification of cholesterol ester and phospholipid hydroperoxides and diacyl peroxides. Extensive studies of a series of cholesterol esters using CIS-MS revealed the following: (1) Cholesterol esters with equal number of double bonds as the internal standard showed a linear relative response in the mass spectrometer while compounds with non-equal numbers of double bonds gave a nonlinear relative response. (2) Complex adducts containing cholesterol ester, silver ion, AgF, AgBF(4), and 2-propanoxide form when silver is in molar excess of cholesterol esters, reducing the [M + Ag](+) signal.