by Dr. Hasan Usmani
Ranibizumab (Lucentis, Genentech) is a recombinant, humanised, monoclonal antibody fragment with a molecular weight of 48KD. It has been designed to bind to and inhibit all isoforms of VEGF-A (non-selective).
It was licensed in the United States in 2006 and in the EU and United Kingdom in Feb 2007
Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab
in the Treatment of Neovascular AMD (MARINA)
· Phase III, multi-centre, randomised, double masked, sham injection-controlled trial
· 716 patients, US
· Randomised 1:1:1 to Ranibizumab 0.3 or 0.5mg or sham once a month for 24 months
· Minimally classic (approximately 1/3 of total) or occult CNV (approximately 2/3 of total)
· VA 6/12 – 6/96
· Previously received
o subfoveal laser treatment
o verteporfin photodynamic therapy
o experimental treatments for wet AMD
· PDT therapy allowed if
o converted to predominantly classic disease while on the study
o had small, active minimally classic or occult lesions and lost 20 letters or more in visual acuity on two consecutive physician evaluations.
o 11 % (25/238) control group vs. 0.4 % (1/238) of patients in the 0.3 mg Ranibizumab group vs. 0% in 0.5 mg Ranibizumab group
· Proportion of subjects losing less than 15 ETDRS letters at one year.
· Change in VA from baseline
· Maintaining vision: patients losing fewer than 15 letters
o 95% (452/478) of treated vs. 62 % (148/238) of control group (p<.0001)
· Improving vision: patients gaining 15 letters or more
o 25% (59/238) of 0.3 mg Ranibizumab vs. 34 % (81/240) of 0.5 mg of Ranibizumab vs. 5 % (11/238) of controls
· Other findings:
o Difference between treated (both doses) and controls
· mean change in visual acuity from baseline = 17 letters
o Visual acuity > 6/12 at 12 months
· Nearly 40 % (188/478) of treated vs. 11 % (26/238) of controls
o Average number of letters gained or lost at 12 months
· 7 letters gained by treated vs. 10.5 letters lost by controls
Analysis of the one-year data:
· Adverse events were similar to those seen in earlier trials of Ranibizumab.
· Ocular side effects that were more common to the treatment arm vs. controls:
· Subconjunctival hemorrhage
· Eye pain
· Vitreous floaters.
· Uveitis (<1% )
· Endophthalmitis (<1%)
· Serious non-ocular adverse events:
o no significant difference in treated vs. controls
· Rosenfeld PJ, Brown DM, Heier JS, Boyer DS, Kaiser PK, Chung CY, Kim RY; MARINA Study Group, Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 2006 Oct 5;355(14):1419-31.