A Phase III clinical trial of the drug Ranibizumab ( Lucentis ) met its primary efficacy endpoint of maintaining vision in patients with wet age-related macular degeneration (AMD ).

Approximately 95 percent of patients maintained or improved vision ( defined as a loss of less than 15 letters in visual acuity ) at one year when treated with Lucentis injections compared to approximately 62 percent of those treated in the control arm ( p<0.0001 ).
Patients treated with Lucentis for 12 months had, on average, a significant improvement in visual acuity compared to their visual acuity at study entry, an important secondary endpoint, while the control group demonstrated a substantial decrease in mean visual acuity from baseline to 12 months.

A preliminary analysis of the data showed that adverse events were similar to those seen in earlier trials of Lucentis.
Common side effects occurring in the Lucentis arms more frequently than in the control group were mild to moderate and included conjunctival hemorrhage, eye pain and vitreous floaters.
Serious ocular adverse events occurring more frequently in Lucentis-treated patients were rare ( <1% ) and included uveitis and endophthalmitis.
There appeared to be no imbalance in serious non-ocular adverse events.

Lucentis is a humanized antibody fragment developed at Genentech and designed to bind and inhibit Vascular Endothelial Growth Factor A ( VEGF-A ), a protein that is believed to play a critical role in angiogenesis.

MARINA is a Phase III study of 716 patients in the United States with minimally classic or occult wet AMD who were randomized 2:1 to receive intravitreal Lucentis injections or a control regimen.
The control regimen consisted of a sham injection, meaning the treating physician prepares and anesthetizes the patient’s eye but does not perform an injection.
Patients treated with Lucentis were further randomized to receive either a 0.3 mg or 0.5 mg dose of Lucentis once a month for two years.

Exclusion criteria included prior subfoveal laser treatment, Verteporfin photodynamic therapy ( PDT ) or experimental treatments for wet AMD.
Visual acuity was measured using the Early Treatment of Diabetic Retinopathy ( ETDRS ) chart, the standard method of quantifying visual acuity.

Age-related macular degeneration ( AMD ) is a major cause of painless central visual loss and is the leading cause of blindness for people over the age of 60.
The National Eye Institute estimates that there are 1.6 million people with AMD in the United States alone and that this prevalence will grow to 2.95 million by 2020.
AMD occurs in two forms: dry and wet.
The dry form is associated with atrophic cell death of the central retina or macula, which is required for fine vision used for activities such as reading, driving or recognizing faces.
The wet form is caused by growth of abnormal blood vessels also known as choroidal neovascularization ( CNV ) or ocular angiogenesis under the macula.
These vessels leak fluid and blood and cause scar tissue that destroys the central retina. This results in a deterioration of sight over a period of months to years.

Source: Genentech, 2005


XagenaMedicine2005