Monday, Nov 7, 2005
South San Francisco, Calif. -- November 7, 2005 --Genentech, Inc. (NYSE: DNA) announced today that a second Phase III clinical study of the investigational drug Lucentis (ranibizumab), ANCHOR, met its primary efficacy endpoint of maintaining vision in patients with the wet form of age-related macular degeneration (AMD). Approximately 94 percent of patients treated with 0.3 mg of Lucentis and 96 percent of those treated with 0.5 mg of Lucentis maintained or improved vision (defined as a loss of less than 15 letters in visual acuity) compared to approximately 64 percent of those treated with verteporfin (Visudyne®) photodynamic therapy (PDT) [p0.0001] during the first year of the two-year study. The Lucentis treatment groups further demonstrated a statistically significant difference from the control arm in an important secondary endpoint: mean change in visual acuity from baseline to month 12. On average, patients treated with Lucentis improved, while patients treated with PDT declined. One-year data from the ANCHOR study will be presented at an upcoming medical meeting.
Preliminary safety findings were consistent with those observed in the other Phase III pivotal study of Lucentis, MARINA. Data from both Phase III studies will be submitted to the U.S. Food and Drug Administration (FDA) as part of the Biologics License Application (BLA) for Lucentis that the company plans to file in December 2005. Genentech will request Priority Review designation at the time of submission.
"Lucentis is the first potential therapy for wet AMD to improve vision in two pivotal Phase III trials and demonstrate a clinical benefit over PDT in a head-to-head study," said Hal Barron, M.D., Genentech senior vice president, Development and chief medical officer. "Based on these compelling results and current unmet medical need, all patients in the ANCHOR study will have access to Lucentis during the remainder of the trial."
ANCHOR (ANti-VEGF Antibody for the Treatment of Predominantly Classic CHORoidal Neovascularization in AMD) is a Phase III randomized, multi-center, double-masked, active-treatment controlled study comparing two different doses of Lucentis to PDT in 423 patients with predominantly classic wet AMD. Patients were randomized 2:1 to receive intravitreal Lucentis injections (0.3 mg or 0.5 mg dose) once a month or PDT every three months for two years. Exclusion criteria included prior subfoveal laser treatment, 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. The study is ongoing in the United States, Europe and Australia.
Common ocular adverse side effects that occurred more frequently in the Lucentis arms than in the control group were mild to moderate and included conjunctival hemorrhage, eye pain, increased intraocular pressure and vitreous floaters. Serious ocular adverse events that occurred more frequently in the Lucentis-treated arms were uncommon and included endophthalmitis (approximately 1 percent). Among non-ocular serious adverse events, the frequency of cerebral vascular events was equal across all three arms. The frequency of myocardial infarctions was slightly higher in patients treated with 0.5 mg of Lucentis than in the other two arms, although this difference was not statistically significant.
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).
Additional Phase III Studies
SAILOR (Safety Assessment of Intravitreal Lucentis for AMD) is a Phase IIIb clinical study of Lucentis for patients with all subtypes of new or recurrent active subfoveal wet AMD. It is a one-year study designed to evaluate the safety of two different doses (0.3 mg and 0.5 mg) of Lucentis administered once a month for three months and thereafter as needed based on criteria-based re-treatment options. The study will be conducted at more than 100 sites in the United States and will enroll approximately 5,000 patients. Enrollment in the SAILOR study began in November 2005.
Genentech is also conducting PIER (A Phase IIIb, Multicenter, Randomized, Double-Masked, Sham Injection-Controlled Study of the Efficacy and Safety of Ranibizumab in Subjects with Subfoveal Choroidal Neovasularization with or without Classic CNV Secondary to Age-Related Macular Degeneration) with 184 patients in the United States. In this trial, Lucentis is administered once per month for the first three months followed thereafter by doses once every three months for a total of 24 months. Enrollment in this study is complete and preliminary results are expected in the first half of 2006.
Earlier this year, Genentech announced positive preliminary one-year Phase III data on Lucentis from MARINA (Minimally classic/occult trial of the Anti-VEGF antibody Ranibizumab In the treatment of Neovascular AMD), a two-year study of 716 patients with minimally classic or occult wet AMD. Nearly 95 percent of patients treated with Lucentis maintained or improved vision at 12 months. Additional one-year results include:
In October, Genentech announced that patients in the sham arm of the MARINA study would be crossed over to active treatment with Lucentis.
An analysis of the one-year data showed that adverse events were similar to those seen in earlier trials of Lucentis. Common side effects that occurred more frequently in the Lucentis arms 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 infrequent (1 percent) and included uveitis and endophthalmitis. There appeared to be no imbalance in serious non-ocular adverse events.
Lucentis (ranibizumab) is a humanized therapeutic antibody fragment developed at Genentech and designed to bind and inhibit VEGF-A, a protein that is believed to play 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 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.
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-A protein is believed to play 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 http://www.gene.com.
This press release contains forward-looking statements regarding the expected time frame for the Lucentis BLA filing and the PIER trial results. Actual results could differ materially. Among other things, the time frame for the trial results could be affected by unexpected safety or efficacy issues, additional time requirements to achieve study endpoints or for data analysis, or discussions with the FDA; and the time frame for the BLA filing could be affected by all of the foregoing and additional time requirements for BLA preparation, the need for additional clinical studies, or FDA actions or delays. Genentech disclaims any obligation and does not undertake to update or revise the forward-looking statements in this press release.