Ranibizumab is a recombinant, humanized, IgG1 monoclonal antibody fragment
(Fab) that neutralizes all active forms of vascular endothelial growth factor
A (VEGF-A), and it is indicated for the treatment of neovascular age-related
macular degeneration (AMD). It consists of a nonbinding human sequence
and a high-affinity binding epitope (Fab fragment) derived from the mouse. The
full-length RhuMab VEGF (bevacizumab) was launched previously by Genentech
for the treatment of colorectal cancer. Both the antibody fragment and the
full-length antibody bind to and inhibit all active forms of VEGF-A and are
derived from the same mouse monoclonal antibody. However, ranibizumab has
been genetically engineered through a process of selective mutation to increase
its affinity for binding and inhibiting the growth factor.
Ranibizumab, sold under the brand name Lucentis among others, is a monoclonal antibody fragment (Fab) created from the same parent mouse antibody as bevacizumab. It works by keeping new blood vessels from forming under the retina (a sensory membrane that lines the inside of the eye). In people with certain types of eye disorders, new blood vessels grow under the retina where they leak blood and fluid.
Ranibizumab was developed by Genentech and marketed by them in the United States, and elsewhere by Novartis, under the brand name Lucentis. Ranibizumab (Lucentis) was approved for medical use in the United States in June 2006, and in the European Union in January 2007.
Ranibizumab, a humanized antigen binding portion of a murine anti- VEGF monoclonal antibody with a mature high affinity for all VEGF isoforms, has been approved as an intravitreal treatment for neovascular AMD and is the first such treatment to improve visual acuity (VA) in neovascular AMD.
CRUISE is multicenter, randomized, double-masked, sham injectioncontrolled Phase III study of 392 participants designed to assess the efficiency and safety profile of ranimizumab for macular edema associated to CRVO. The month 6 result showed that 46.2% (61/132) of patients received 0.3 mg of ranimizumab and 47.7% (62/130) received 0.5 mg of ranimizumab had their vision improved by 15 letters or more compared to 16.9% (22/130) of patients receiving sham injections and mean gain was observed beginning at day seven with an 8.8 and 9.3 letter gain in the 0.3 mg and 0.5 mg study arms of ranimizumab, respectively, compared with 1.1 letters in the sham injection arm.
antiangiogenic monoclonal antibody macular degeneration therapy
Studies in monkeys demonstrates that after a single intravitreal administration, Ranibizumab can distribute rapidly to the retina (6–24h). Ranibizumab can rapidly penetrate through the retina to reach the choroid, just 1h after intravitreal administration in rabbits[1].In a study comparing the pharmacokinetics of 0.5mg of intravitreal Ranibizumab with 1.25mg of intravitreal Bevacizumab in the rabbit, the vitreous half-life of Ranibizumab is 2.88 days, shorter than the Bevacizumab half-life of 4.32 days. Peak concentrations in the aqueous humor of the treated eye at 3 days following treatment are 37.7μg/ml for Bevacizumab and 17.9μg/ml for Ranibizumab, respectively[1].
