A single-masked Phase I/II clinical study of the investigational drug Lucentis ( Ranibizumab ) met its primary efficacy endpoint of maintaining vision in patients with wet age-related macular degeneration ( AMD ) when used in combination with Verteporfin ( Visudyne ) photodynamic therapy ( PDT ).

Approximately 90 percent of patients maintained or improved vision ( defined as a loss of less than 15 letters in visual acuity ) when treated with the combination of Lucentis and PDT compared to approximately 68 percent of those treated in the control arm of PDT alone ( p = 0.0003 ).
Patients treated with Lucentis plus PDT at 12 months had, on average, a significant improvement in visual acuity compared to visual acuity at study entry, an important secondary endpoint, while the PDT-alone group demonstrated a decrease in mean visual acuity from baseline to 12 months.

A preliminary analysis of the data showed there was an increased risk of the serious ocular adverse event uveitis in patients treated with Lucentis in combination with PDT compared to patients treated with PDT alone.
An amendment to the study protocol was made after data safety monitoring identified this imbalance. After uveitis, endophthalmitis was the second most common ocular serious adverse event occurring in patients treated with Lucentis.
Among non-ocular serious adverse events, the frequency of cerebral vascular events was slightly higher in those treated with Lucentis, while the frequency of myocardial infarctions was slightly higher in the PDT-alone arm. In both cases, the difference between groups was not statistically significant.

Genentech and Novartis Pharma recently announced top-line positive results from the Phase III MARINA study.
A preliminary analysis of the MARINA 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 in the MARINA study.

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

The FOCUS ( RhuFab V2 Ocular Treatment Combining the Use of Visudyne to Evaluate Safety ) trial is a Phase I/II randomized, single-masked study evaluating the safety, tolerability and efficacy of Lucentis in combination with PDT in 162 patients with predominantly classic subfoveal wet age-related macular degeneration.

In this study, patients were randomized 2:1 to receive PDT followed by either 0.5 mg injections of Lucentis or sham injections for 23 months. To perform a sham injection, the treating physician prepares and anesthetizes the patient's eye but does not perform an injection. The FOCUS study was conducted at 25 sites in the United States.

Source: Genentech, 2005

XagenaMedicine2005