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Magdalena G. Krzystolik, MD; Mehran A. Afshari, MD; Anthony P. Adamis, MD; Jacques Gaudreault, PhD; Evangelos S. Gragoudas, MD; Norman A. Michaud, MS; Wenjun Li, MS; Edward Connolly, BS; Charles A. O'Neill, PhD; Joan W. Miller, MD

Arch Ophthalmol. 2002;120:338-346.

Objective  To evaluate the safety and efficacy of intravitreal injections of an antigen-binding fragment of a recombinant humanized monoclonal antibody directed toward vascular endothelial growth factor (rhuFab VEGF) in a monkey model of choroidal neovascularization (CNV).

Methods  In phase 1 of the study, each animal received intravitreal injections, 500 µg per eye, of rhuFab VEGF in one eye (prevention eye), while the contralateral eye received rhuFab VEGF vehicle (control eye) at 2-week intervals. On day 21, laser photocoagulation was performed to induce CNV. In phase 2, the vehicle-treated eye was crossed over and both eyes received 500 µg of rhuFab VEGF beginning 21 days following laser-induced injury at days 42 and 56. The eyes were monitored by ophthalmic examinations, color photographs, and fluorescein angiography.

Results  rhuFab VEGF did not cause any ocular hemorrhages. All eyes treated with rhuFab VEGF developed acute anterior chamber inflammation within 24 hours of the first injection that resolved within 1 week, and this inflammation was less severe with subsequent injections. The incidence of CNV, defined angiographically, was significantly lower in the prevention eyes than the control eyes (P<.001). Subsequent treatments were associated with less leakage in eyes with established CNV that were crossed over from the control eyes to the treatment eyes (P = .001).

Conclusions  Intravitreal rhuFab VEGF injections prevented formation of clinically significant CNV in cynomolgus monkeys and decreased leakage of already formed CNV with no significant toxic effects.

Clinical Relevance  This study provides the nonclinical proof of principle for ongoing clinical studies of intravitreally injected rhuFab VEGF in patients with neovascular age-related macular degeneration.

From Retina Consultants, Providence, RI (Dr Krzystolik); Angiogenesis Laboratory and Laser Laboratory, Retina Research Institute, Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston (Drs Afshari, Adamis, Gragoudas, and Miller and Messrs Michaud, Li, and Connolly); and Pharmacological Sciences, Genentech, Inc, South San Francisco, Calif (Drs Gaudreault and O'Neill). This work was supported in part by Genentech, Inc.

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