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Comprehensive biophysical and functional study of ziv-aflibercept: characterization and forced degradation.

ABSTRACT: Aflibercept (AFL) is an Fc fusion protein used in the treatment of colorectal cancers and different ophthalmological diseases. There are two medicines in which AFL is the active substance: Zaltrap and Eylea, referred as ziv-AFL and AFL respectively. No proper accelerated degradation studies were published on either AFL or ziv-AFL. These studies are essential during research, development and manufacturing stages. Here, we characterized ziv-AFL and submitted it to different stress conditions: light, 60?°C, freeze-thaw cycles, changes in pH, high hypertonic solution and strong denaturing conditions. We used an array of techniques to detect aggregation (SE-HPLC/DAD and DLS), changes in secondary structure (Far-UV circular dichroism), changes in conformation or tertiary structure (Intrinsic tryptophan fluorescence) and alterations in functionality (ELISA). Results indicate that aggregation is common degradation pathway. Two different types of aggregates were detected: dimers and high molecular weight aggregates attributed to ?-amyloid-like structures. Secondary structure was maintained in most of the stress tests, while conformation was altered by almost all the tests except for the freeze-thaw cycles. Functionality, evaluated by its immunochemical reaction with VEGF, was found to be stable but with decrease when exposed to light and with likely partial inactivation of the drug when pH was altered.

SUBMITTER: Hermosilla J

PROVIDER: S-EPMC7021693 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Comprehensive biophysical and functional study of ziv-aflibercept: characterization and forced degradation.

Hermosilla Jesús J Pérez-Robles Raquel R Salmerón-García Antonio A Casares Salvador S Cabeza Jose J Bones Jonathan J Navas Natalia N

Scientific reports 20200214 1

Aflibercept (AFL) is an Fc fusion protein used in the treatment of colorectal cancers and different ophthalmological diseases. There are two medicines in which AFL is the active substance: Zaltrap and Eylea, referred as ziv-AFL and AFL respectively. No proper accelerated degradation studies were published on either AFL or ziv-AFL. These studies are essential during research, development and manufacturing stages. Here, we characterized ziv-AFL and submitted it to different stress conditions: ligh ...[more]

PMID: 32060315

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Project description:BACKGROUND:Myopic choroidal neovascularization (CNV) is the most common sight-threatening complication associated with high myopia. The present study evaluated the efficacy and safety of the intravitreal injection of ziv-aflibercept in patients with myopic CNV. METHODS:This prospective interventional study was conducted on 20 eyes of 20 patients with active myopic CNV. Twelve patients were 40?years or older. This study was performed in the Ophthalmology Department of Tanta University Eye Hospital, Tanta University, Egypt. Optical coherence tomography (OCT) was performed for all patients at baseline and monthly after injection during the 6-month follow up period. The main outcome measures were changes in BCVA and CMT. The exploratory outcome measures were CNV size, IOP and the number of injections needed in each age group during the study period. RESULTS:Patients with myopic CNV younger than 40?years needed fewer injections (2.00?±?0.76) than patients older than 40?years (2.50?±?1.00), with no statistical significance detected between the two groups (p-value 0.246). CNV was smaller in the younger age group (p-value 0.209), best corrected visual acuity (BCVA) improved significantly in the younger and older age groups (p-values 0.001 and 0.028, respectively), and central macular thickness (CMT) decreased significantly after 6?months, from 242.88?±?23.83??m to 191.13?±?13.83??m in the younger age group and from 251.33?±?26.60??m to 197.08?±?17.64??m in the older age group (p =?0.001). No significant correlation was found between the final BCVA and either the spherical equivalent or central macular thickness after 6?months, with p-values of 0.135 and 0.145, respectively. No significant changes in IOP were detected in either group after the intravitreal injection. CONCLUSION:Ziv-aflibercept is a highly effective and safe drug in cases of active myopic CNV; however, a larger number of patients and a longer follow-up period are needed to confirm our results. This study was retrospectively registered at clinicaltrials.gov (ID: NCT04290195) on 26-2-2020.

Dataset Information

Comprehensive biophysical and functional study of ziv-aflibercept: characterization and forced degradation.

Publications

Comprehensive biophysical and functional study of ziv-aflibercept: characterization and forced degradation.

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