Tuesday, May 31, 2005
South San Francisco, Calif. -- May 31, 2005 --Genentech, Inc. (NYSE: DNA) announced today that 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. One-year data from the trial will be presented at the 23rd Annual Meeting of the American Society of Retina Specialists (ASRS), July 16 to 20 in Montreal, Canada.
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.
"We are excited to see a statistically significant improvement in vision for patients with wet AMD in a second trial in which patients were treated with Lucentis," said Hal Barron, M.D., Genentech's senior vice president, development and chief medical officer.
Genentech and Novartis Pharma AG 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 formation of new blood vessels).
About the Study
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 AMD. 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.
Ongoing Phase III Studies
The MARINA (Minimally classic/ occult trial of the Anti-VEGF antibody RhuFab V2 In the treatment of Neovascular AMD) study is a randomized, multi-center, double-masked, sham-injection controlled study evaluating the safety and efficacy of two different doses of Lucentis in 716 patients with minimally classic or occult subfoveal wet AMD.
Genentech and Novartis Pharma AG are conducting an additional Phase III study of Lucentis, ANCHOR (ANti-VEGF Antibody for the Treatment of Predominantly Classic CHORoidal Neovascularization in AMD). This is a randomized, multi-center, double-masked, active treatment controlled study comparing two different doses of Lucentis to PDT in 423 patients. The trial is ongoing in the United States, Europe and Australia with predominantly classic wet AMD. Results from this study are expected in the fourth quarter of 2005.
Genentech is conducting an additional Phase IIIb study, PIER (A Phase IIIb, Multicenter, Randomized, Double-Masked, Sham Injection-Controlled Study of the Efficacy and Safety of Ranibizumab in Subjects with Subfoveal Choroidal Neovascularization with or without Classic CNV Secondary to Age-Related Macular Degeneration), a randomized, double-masked, sham injection-controlled study comparing one of two doses of Lucentis to sham injections in 184 patients in the United States with wet AMD. In this trial, Lucentis is administered once per month for the first three doses followed thereafter by doses once every three months for two years. Results from this study are expected in the first half of 2006.
Lucentis (ranibizumab) is a humanized therapeutic antibody fragment developed at Genentech and designed to bind and inhibit VEGF-A, a protein that plays a critical role in angiogenesis (the formation of new blood vessels). Lucentis is designed to block new blood vessel growth and leakiness, which lead to wet AMD disease progression and vision loss.
Lucentis is being developed by Genentech and the Novartis Ophthalmics Business Unit. Genentech retains commercial rights for Lucentis in North America (United States, Canada and Mexico). Novartis has exclusive commercialization rights for the rest of the world.
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. 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.
Genentech is a leader in research and product development in the area of angiogenesis, the process by which new blood vessels are formed. In 1989, Napoleone Ferrara, M.D., and a team of scientists at Genentech conducted seminal work in the field, which resulted in the identification and cloning of a gene termed Vascular Endothelial Growth Factor (VEGF), now known as VEGF-A. The VEGF protein plays a critical role in angiogenesis, and serves as one of the key contributors to physiological or pathological conditions that can stimulate the formation of new blood vessels. The process of angiogenesis is normally regulated throughout development and adult life, and the uncontrolled growth of new blood vessels is an important contributor to a number of pathologic conditions, including wet AMD.
Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes biotherapeutics for significant unmet medical needs. A considerable number of the currently approved biotechnology products originated from, or are based on, Genentech science. Genentech manufactures and commercializes multiple biotechnology products directly in the United States and licenses several additional products to other companies. The company has headquarters in South San Francisco, Calif., and is traded on the New York Stock Exchange under the symbol DNA. For additional information about the company, please visit www.gene.com.
The statements made in this press release relating to the expected time frame for results from the Phase III ANCHOR and PIER trials are forward-looking and actual results could differ materially. Among other things, the timing could be affected by additional time requirements for data analysis or discussions with the FDA.