RANIBIZUMAB

by Dr. Hasan Usmani

Introduction

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)

Method

·         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

Inclusion Criteria:

·         Minimally classic (approximately 1/3 of total) or occult CNV (approximately 2/3 of total)

·         VA 6/12 – 6/96

Exclusion criteria

·         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

Primary endpoint

·         Proportion of subjects losing less than 15 ETDRS letters at one year.

Secondary endpoint

·         Change in VA from baseline

Results

·         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

Adverse Effects

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:

o        Minor

·         Subconjunctival hemorrhage

·         Eye pain

·         Vitreous floaters.

o        Serious

·         Uveitis (<1% )

·         Endophthalmitis (<1%)

·         Serious non-ocular adverse events:

o        no significant difference in treated vs. controls

Further reading

·         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.