Short-Term Safety Profile of Intravitreal Ziv-Aflibercept

Abstract

Single intravitreal injections of ziv-aflibercept into eyes with neovascular age-related macular degeneration appear to be safe through 1 month. Ziv-aflibercept could become a safe, low-cost therapy for macular diseases in developing countries and in those where intravitreal aflibercept (Eylea) is not available.

Three-month outcome of intravitreal ziv-aflibercept in eyes with diabetic macular oedema

“…The compounded ziv-aflibercept drug was stable for 4 weeks as shown indirectly by good clinical response in the current study and directly by VEGF assays showing no loss of VEGF blockade at 1-month storage 12. The current study was carried out using polycarbonate barrel syringes that have poor binding to protein and excellent safety profile 12…”

“…Several case reports and small case series dealing with age-related macular degeneration or central retinal vein occlusion8–13 experienced visual gains without change in the electroretinogram recordings. Electroretinogram analysis in 12 subjects with wet age-related macular degeneration revealed no alterations 1 month after a single intravitreal ziv-aflibercept injection 12. The only mention of the use of ziv-aflibercept in DME comes from one phase I study:9 two patients with DME were treated in one eye and examined 1 week postinjection: the first had a decrease in CMT of 64 μm from 508 to 443 μm with visual improvement from 20/800 to 20/100; the second had a decrease in CMT of 352 μm from 720 to 368 μm with visual improvement from 20/800 to 20/200 at 1 week.…”

“…Hence, we used ziv-aflibercept (Zaltrap, Regeneron Pharmaceuticals), United States Food and Drug Administration-approved (since 9 August 2012) aflibercept for oncology, as intravitreal therapy. We compounded it for use in patients who cannot afford the ophthalmic version of aflibercept (Eylea) on a compassionate basis after lack of toxicity in the laboratory and in case reports8–11 and phase I clinical studies, one involving DME 12 13…”

Flattening of a Treatment-Resistant Retinal Pigment Epithelial Detachment After a Single Intravitreal Injection of Ziv-Aflibercept

“…Short-term safety of intravitreal ziv-aflibercept has been reported in small case series, 7,8 and 1-month electroretinographic studies detected no postinjection abnormalities. 9 Flattening of neovascular PEDs with anti-VEGF therapy would seem to be a desirable morphologic effect, but the long-term advantages of this outcome remain unclear. Neither Chan 1 nor Khanani (subset analysis of HARBOR trial, ARVO 2015, E-abstract 5363) found a visual acuity benefit when 2.0-mg ranibizumab significantly decreased PED height compared with that achieved with 0.5-mg ranibizumab.…”

Investigational drugs for retinal vein occlusion

“…However, the difference in osmolarity between aflibercept and ziv-aflibercept may impair retinal function, and so the off-label use of zivaflibercept in RVO needs further assessment. It has been reported that off-label use of ziv-aflibercept improves VA without ocular toxicity and may offer a cheaper alternative to aflibercept, [43,44] in the same way that bevacizumab is cheaper than ranibizumab. Ziv-aflibercept is supplied at 25 mg/ml in single-use vials of 100 mg in 4 ml or 200 mg in 8 ml of 0.1% polysorbate 20, 100 mM sodium chloride, 5 mM sodium citrate, 5 mM sodium phosphate, and 20% sucrose in water for injection USP, pH 6.2.…”