Monday, Jul 18, 2005
Montreal -- July 18, 2005 --Genentech, Inc. (NYSE: DNA) announced today positive preliminary results from a single-masked Phase I/II clinical study of the investigational anti-VEGF drug Lucentis (ranibizumab) in combination with verteporfin (Visudyne®) photodynamic therapy (PDT) compared to PDT alone in 162 patients with wet age-related macular degeneration (AMD). In addition to meeting the study's primary efficacy endpoint of maintaining vision in patients with wet AMD, secondary endpoint results show there was a 13 letter difference in mean change in visual acuity from study entry between the two treatment groups as measured by the Early Treatment of Diabetic Retinopathy (ETDRS) eye chart. At 12 months, patients treated with Lucentis and PDT gained an average of five letters in visual acuity compared to study entry, while those in the control group lost an average of eight letters. Twenty-four percent (25/105) of patients treated with Lucentis in combination with PDT versus 5 percent (3/56) of patients treated with PDT alone improved vision by 15 letters or more compared to study entry. One-year data from the study were presented at the 23rd Annual Meeting of the American Society of Retina Specialists (ASRS), in Montreal, Canada.
"In this study, patients treated with Lucentis not only experienced an improvement in vision, but were significantly less likely to require retreatment with PDT during the first year of study," said Hal Barron, M.D., Genentech senior vice president, development and chief medical officer.
An analysis of the one-year 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 higher in those treated with Lucentis, while the frequency of myocardial infarctions was higher in the PDT-alone arm. In both cases, the difference between groups was not statistically significant. Severe vision loss (defined as a loss of 30 letters or more) was uncommon (1/105) among those treated with Lucentis and PDT compared with 9 percent (5/56) for those treated with PDT alone.
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 (the formation of new blood vessels). Earlier this month, Genentech announced it has requested a fast-track designation for the Lucentis development program in wet AMD. If granted by the U.S. Food and Drug Administration (FDA), this could enable Genentech to begin a rolling Biologics License Application filing by the end of 2005.
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. The FOCUS study was conducted at 25 sites in the United States.
In this study, 162 patients with predominantly classic subfoveal wet AMD 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 the injection. All patients received initial treatment with PDT but were only retreated at the treating physician's discretion based on the Visudyne package insert.
Ongoing Phase III Studies
Genentech and Novartis Pharma AG recently announced positive results from the Phase III MARINA (Minimally classic/occult trial of the Anti-VEGF antibody RhuFab V2 In the treatment of Neovascular AMD) study, 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. Nearly 95 percent (452/478) of patients treated with Lucentis lost fewer than 15 letters compared to baseline, compared with 62 percent (148/238) for the sham injection control group.
An 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 uncommon (1 percent) and included uveitis and endophthalmitis. There appeared to be no imbalance in serious non-ocular adverse events in the MARINA study.
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 quarter of 2006.
Genentech recently began enrollment in the HORIZON Phase III open-label extension study, which allows eligible patients who have completed participation in certain other Lucentis clinical studies to continue to receive the investigational drug.
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 in the United States and Canada. 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. In Canada, the Foundation Fighting Blindness estimates that more than 800,000 people are affected by the disease.
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.
This press release contains forward-looking statements regarding the expected time frame for results from the Phase III ANCHOR and PIER trials and for filing a Biologics License Application (BLA) for Lucentis, and actual results could differ materially. Among other things, the timing of the trial results could be affected by additional time requirements for data analysis or discussions with the FDA, and the timing for the BLA filing could be affected by all of the foregoing and by additional time requirements for BLA preparation, need for additional clinical studies, or FDA actions or delays.