{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:23:04Z","timestamp":1792628584607,"version":"4.5.0"},"reference-count":37,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2023,4,1]],"date-time":"2023-04-01T00:00:00Z","timestamp":1680307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,4,1]],"date-time":"2023-04-01T00:00:00Z","timestamp":1680307200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Ocular Pharmacology and Therapeutics"],"published-print":{"date-parts":[[2023,4,1]]},"abstract":"<jats:sec>\n                    <jats:title>Purpose:<\/jats:title>\n                    <jats:p>\n                      Bevacizumab-bvzr (Zirabev\n                      <jats:sup>\u00ae<\/jats:sup>\n                      ), a recombinant humanized monoclonal antibody targeting vascular endothelial growth factor and a biosimilar to bevacizumab, is approved for intravenous administration for various indications worldwide. The objectives of this study were to evaluate the ocular toxicity, systemic tolerability, and toxicokinetics (TKs) of bevacizumab-bvzr following repeat intravitreal (IVT) injection to cynomolgus monkeys.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Male monkeys were administered saline, vehicle, or bevacizumab-bvzr at 1.25\u2009mg\/eye\/dose once every 2 weeks (3 doses total) for 1 month by bilateral IVT injection, followed by a 4-week recovery phase to evaluate the reversibility of any findings. Local and systemic safety was assessed. Ocular safety assessments included in-life ophthalmic examinations, tonometry (intraocular pressure, IOP), electroretinograms (ERGs), and histopathology. In addition, concentrations of bevacizumab-bvzr were measured in serum and in ocular tissues (vitreous humor, retina, and choroid\/retinal pigment epithelium) and ocular concentration-time profiles and serum TKs were evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Bevacizumab-bvzr was tolerated locally and systemically, with an ocular safety profile comparable to the saline or vehicle control group. Bevacizumab-bvzr was observed in both serum and in the evaluated ocular tissues. There were no bevacizumab-bvzr-related microscopic changes or effects on IOP or ERGs. Bevacizumab-bvzr-related trace pigment or cells in vitreous humor (in 4 of 12 animals; commonly associated with IVT injection) and transient, nonadverse, mild ocular inflammation (in 1 of 12 animals) were noted upon ophthalmic examination and fully reversed during the recovery phase.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Bevacizumab-bvzr was well tolerated via biweekly IVT administration in healthy monkeys, with an ocular safety profile comparable to saline or its vehicle control.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/jop.2022.0059","type":"journal-article","created":{"date-parts":[[2023,3,7]],"date-time":"2023-03-07T09:50:56Z","timestamp":1678182656000},"page":"215-224","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Ocular Safety and Toxicokinetics of Bevacizumab-bvzr (Zirabev), a Bevacizumab Biosimilar, Administered to Cynomolgus Monkeys by Intravitreal Injection"],"prefix":"10.1177","volume":"39","author":[{"given":"Marjorie A.","family":"Peraza","sequence":"first","affiliation":[{"name":"Drug Safety Research and Development, Pfizer Inc., Cambridge, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Hurst","sequence":"additional","affiliation":[{"name":"Biomedicine Design, Pharmacokinetics, Dynamics, and Metabolism, Pfizer Inc., Groton, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhu","family":"Huang","sequence":"additional","affiliation":[{"name":"Drug Safety Research and Development, Pfizer Inc., San Diego, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard S.","family":"Buetow","sequence":"additional","affiliation":[{"name":"Drug Safety Research and Development, Pfizer Inc., San Diego, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Lickteig","sequence":"additional","affiliation":[{"name":"Charles River Laboratories, Inc., Reno, Nevada, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Dan","family":"Lavach","sequence":"additional","affiliation":[{"name":"Charles River Laboratories, Inc., Reno, Nevada, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denzil F.","family":"Frost","sequence":"additional","affiliation":[{"name":"Charles River Laboratories, Inc., Reno, Nevada, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret E.","family":"Collins","sequence":"additional","affiliation":[{"name":"Charles River Laboratories, Inc., Reno, Nevada, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rani S.","family":"Sellers","sequence":"additional","affiliation":[{"name":"Drug Safety Research and Development, Pfizer Inc., Pearl River, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Matsumoto Smith","sequence":"additional","affiliation":[{"name":"Drug Safety Research and Development, Pfizer Inc., San Diego, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2023,4,4]]},"reference":[{"key":"e_1_3_7_2_2","unstructured":"European Medicines Agency. 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