Ziv-aflibercept in Ocular Disease Requiring Anti-VEGF Injection

Summary

Background/aims: Aflibercept is an approved therapy for neovascular macular degeneration (AMD), diabetic macular edema (DME), retinal vein occlusion and other retinal conditions. Ziv-aflibercept is also approved by FDA and is extremely cost-effective relative to the expensive same molecule aflibercept. In vitro and in vivo studies did not detect toxicity to the retinal pigment epithelium cells using the approved cancer protein, ziv-aflibercept. Ziv-aflibercept had no loss of anti-VEGF activity when kept at 4°C in polycarbonate syringes over 4 weeks. Similar to bevacizumab, compounded ziv-aflibercept would yield a tremendous saving compared to aflibercept or ranibizumab. Phase I studies and case reports did not report any untoward toxic effects but attested to the clinical efficacy of the medication. Our purpose is to ascertain the long-term safety and efficacy in various retinal diseases of intravitreal ziv-aflibercept. Methods: Prospectively, consecutive patients with retinal disease that require aflibercept (AMD, DME, RVO, and others) will undergo instead the same molecule ziv-aflibercept intravitreal injection of 0.05 ml of fresh filtered ziv-aflibercept (1.25mg). Monitoring of best-corrected visual acuity, intraocular inflammation, cataract progression, and retinal structure by spectral domain OCT to be done initially, one month, 6 months, 1 year, and 2 years after injections. Anticipated Results: Analyze signs of retinal toxicity, intraocular inflammation, or change in lens status, together with best corrected visual acuity and central foveal thickness at 1 month, 6 months, 1 year and 2 year. Anticipated Conclusions: Off label use of ziv-aflibercept improves visual acuity without ocular toxicity and offers a cheaper alternative to the same molecule aflibercept (or lucentis), especially in the third world similar to bevacizumab.

Timeline

Start

2015-03

Primary completion

2019-05

Completion

2019-12

Publications

• Background de Oliveira Dias JR, Xavier CO, Maia A, de Moraes NS, Meyer C, Farah ME, Rodrigues EB. Intravitreal injection of ziv-aflibercept in patient with refractory age-related macular degeneration. Ophthalmic Surg Lasers Imaging Retina. 2015 Jan;46(1):91-4. doi: 10.3928/23258160-20150101-17.
• Results Mansour AM, Al-Ghadban SI, Yunis MH, El-Sabban ME. Ziv-aflibercept in macular disease. Br J Ophthalmol. 2015 Aug;99(8):1055-9. doi: 10.1136/bjophthalmol-2014-306319. Epub 2015 Feb 12.
• Results Mansour AM, Chhablani J, Antonios RS, Yogi R, Younis MH, Dakroub R, Chahine H. Three-month outcome of ziv-aflibercept for exudative age-related macular degeneration. Br J Ophthalmol. 2016 Dec;100(12):1629-1633. doi: 10.1136/bjophthalmol-2015-308319. Epub 2016 Mar 30.
• Mansour AM, Ashraf M, El Jawhari KM, Farah M, Souka A, Sarvaiya C, Singh SR, Banker A, Chhablani J. Intravitreal ziv-aflibercept in diabetic vitreous hemorrhage. Int J Retina Vitreous. 2020 Jan 14;6:2. doi: 10.1186/s40942-019-0204-9. eCollection 2020.
• Mansour AM. Regression of Inflamed Pterygia by Frequent High-Dose Intralesional Ziv-Aflibercept. Cornea. 2017 Aug;36(8):1002-1005. doi: 10.1097/ICO.0000000000001251.

Drugs

Indications