Saturday, Jan 14, 2006
New York -- January 14, 2006 --Genentech, Inc. (NYSE: DNA) announced today positive one-year results from its second pivotal Phase III study of the investigational drug Lucentis (ranibizumab) in patients with wet age-related macular degeneration (AMD). Data from the ANCHOR study comparing Lucentis to verteporfin (Visudyne®) photodynamic therapy (PDT) showed a difference in mean change in visual acuity of 18 letters for patients treated with 0.3 mg of Lucentis and 21 letters for patients treated with 0.5 mg of Lucentis from study entry compared to those treated with PDT at 12 months. In the first year of this two-year study, patients treated with Lucentis gained an average of 8.5 letters in the 0.3 mg dose group and 11 letters in the 0.5 mg dose group compared to patients treated with PDT, who lost an average of 9.5 letters. All visual acuity outcomes were measured by the Early Treatment of Diabetic Retinopathy (ETDRS) eye chart. In November 2005, Genentech announced that the Phase III ANCHOR study met its primary efficacy endpoint of maintaining vision (defined as a loss of less than 15 letters in visual acuity) in patients with wet AMD. One-year data from the ANCHOR study were presented today during Macula 2006, a medical symposium held in New York and sponsored by the Manhattan Eye, Ear & Throat Hospital.
"Lucentis is the first investigational therapy that has shown improved vision, not just a slowing of vision loss, in patients with all types of wet AMD," said Peter K. Kaiser, M.D., director, Clinical Research Center, The Cleveland Clinic Cole Eye Institute, who presented the data today. "As a result, physicians may be one step closer to being able to set a new expectation for the future treatment of this condition."
An analysis of the one-year data showed that adverse events were similar to those seen in earlier trials of Lucentis. Common ocular adverse side effects that occurred more frequently in the Lucentis arms than in the control group were mild to moderate and included conjuctival hemorrhage, increased intraocular pressure, eye pain and vitreous floaters. Serious ocular adverse events that occurred more frequently in the Lucentis-treated arms were uncommon and included endophthalmitis and intraocular inflammation (each reported in less than 1 percent of patients per group). Among non-ocular serious adverse events, the frequency of cerebral vascular events was less than 1 percent of patients per group. The frequency of myocardial infarctions was slightly higher in patients treated with 0.5 mg of Lucentis (2.1 percent) than in the other two arms (0.7 percent).
Additional key clinically meaningful study findings include:
"Through the extensive clinical study program for Lucentis we have now shown a significant improvement in vision compared to Visudyne and in patients with all types of wet AMD," said Hal Barron, Genentech senior vice president, Development and chief medical officer. "We look forward to working with the FDA on our BLA submission and Priority Review request. Given the existing unmet medical need for patients with wet AMD, we are providing access to Lucentis for eligible patients through SAILOR, a Phase IIIb safety study."
In December 2005, Genentech announced that it had submitted a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for the use of Lucentis in the treatment of neovascular wet AMD. The BLA submission, which included a request for Priority (six-month) Review, is based on one-year clinical data on the efficacy and safety of Lucentis from two pivotal Phase III trials, ANCHOR and MARINA, as well as one-year clinical data from the Phase I/II FOCUS trial.
About the Study
ANCHOR (ANti-VEGF Antibody for the Treatment of Predominantly Classic CHORoidal Neovascularization in AMD) is a Phase III randomized, two-year, 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 Diabetic Retinopathy Study (ETDRS) chart, the standard method of quantifying visual acuity. The study is ongoing in the United States, Europe and Australia. Based on the one-year results, patients in the PDT alone arm of the study will have access to Lucentis for the remainder of the study.
Additional Phase III Studies
In November 2005, Genentech began enrollment in a Phase IIIb study, SAILOR, to make Lucentis available to eligible patients. 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 re-treatment criteria. The study will be conducted at more than 100 sites in the United States and will enroll up to 5,000 patients. Those interested in additional information about the study can call toll-free 1-888-662-6728.
In July 2005, Genentech announced positive preliminary one-year results from the pivotal Phase III MARINA study (Minimally classic/occult trial of the Anti-VEGF antibody Ranibizumab In the treatment of Neovascular AMD), a randomized, two-year, 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 wet AMD. Nearly 95 percent of patients treated with Lucentis maintained or improved vision at 12 months. Additional one-year results include:
In October 2005, Genentech announced that patients in the sham arm of the MARINA study would be crossed over to active treatment with Lucentis. Additional one-year data from the MARINA study will be presented at the Macula Society Meeting in February.
Genentech is also conducting PIER (A Phase IIIb, Multi-center, 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) 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 second quarter of 2006.
Lucentis Safety Profile
In clinical trials to date, the most common side effects that occurred more frequently in the Lucentis arms (0.3 mg and 0.5 mg) than in the control arms 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 and intraocular inflammation (less than 1 percent for each). Among non-ocular serious adverse events, cerebral vascular events and myocardial infarctions were observed in all three arms of both the Phase III MARINA and ANCHOR studies. The combined rate of these events in these two studies with monthly dosing was similar in the control and the 0.3 mg Lucentis arms (1.3 percent and 1.6 percent respectively) and slightly higher in the 0.5 mg Lucentis arm (2.9 percent).
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.
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 for diseases or disorders of the eye. Genentech retains commercial rights in the United States and Canada, and Novartis has exclusive commercial rights for the rest of the world.
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 and licenses several additional products to other companies. The company has headquarters in South San Francisco, California and is listed 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 Lucentis as a potential therapy and the expected time frame for the PIER trial results. Such statements are just predictions and involve risks and uncertainties such that actual results may differ materially. Among other things, the time frame for the PIER 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 or FDA actions; and Lucentis as a potential therapy could be affected by all of the forgoing and the failure to receive FDA approval, competition, pricing and the ability to supply product or a product withdrawal. Please also refer to Genentech's periodic reports filed with the Securities and Exchange Commission. Genentech disclaims, and does not undertake, any obligation to update or revise the forward-looking statements in this press release.