Genentech announced preliminary data from the extension phase of an open-label Phase Ib/II randomized, single-agent study with the investigational anti-angiogenesis product, Lucentis (ranibizumab), formerly known as rhuFab V2, for patients with the wet form of age-related macular degeneration (AMD). Lucentis is a humanized, therapeutic antibody fragment that is designed to bind to and inhibit VEGF (vascular endothelial growth factor), a protein that is believed to play a critical role in angiogenesis, the formation of new blood vessels and in regulating vascular permeability.
"The data from this study appear to indicate that most patients not only continued to maintain vision, but improved their vision when Lucentis therapy was extended to six months and beyond," said Hal Barron, FACC, Genentech's vice president, Medical Affairs. "Furthermore, patients initially showing a decline in visual acuity in the usual care group experienced an improvement in visual acuity upon crossing over to receive Lucentis. The fact that visual acuity continued to improve during extended Lucentis treatment suggests that a patient's response can be durable, an important potential benefit for patients with this normally progressive disease."
In the first treatment period (98 days), 64 patients with minimally classic and predominantly classic wet AMD were entered into the single-agent, multi-center trial. Patients were treated every four weeks for four doses (either 300 or 500 micrograms) of Lucentis (n=53) or with usual care of observation or photodynamic therapy (n=11). After Day 98, patients in the usual care group were permitted to cross over to receive Lucentis. All patients were monitored for safety and visual acuity, which is defined as the total number of letters read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart. Stable vision is defined as losing or gaining fewer than 15 letters on the ETDRS chart compared with the baseline.
Of the 53 patients who received Lucentis during the first treatment period, 42 patients continued with Lucentis for the second treatment period with 40 patients completing the study through Day 210. The visual acuity at Day 98 in patients who continued with treatment improved by an average of 7.4 letters (n=20) in the 300 microgram group and 12.6 letters (n=22) in the 500 microgram group. At Day 210, their visual acuity improved further to an average gain of 12.8 letters (n=19) in the 300 microgram group and 15.0 letters (n=21) in the 500 microgram group compared with the baseline.
While patients receiving usual care demonstrated an average loss in visual acuity of 5.1 letters (n=11) at Day 98, those who crossed over to Lucentis improved on the average by 7.3 letters (n=4) and 3.2 letters (n=5) at Day 210 compared with the baseline in the 300 and 500 microgram groups, respectively. Of the 40 patients who were treated with Lucentis for six months and completed the study through Day 210, 97.5 percent (n=39) of patients had stable or improved vision at Day 210, of which 45 percent (n=18) improved 15 letters or more on the ETDRS chart.
The most common side effects from treatment with Lucentis were mild transient, reversible inflammation. Adverse events were similar in the first and extended treatment periods. There were three serious adverse events of endophthalmitis (infection), recurrent uveitis (inflammation) and central retinal vein occlusion, all of which were successfully treated or resolved.