Tuesday, Feb 28, 2006
South San Francisco, Calif. -- February 28, 2006 --Genentech, Inc. (NYSE: DNA) announced today that the U.S. Food and Drug Administration (FDA) has accepted the Biologics License Application (BLA) for the use of Lucentis (ranibizumab) in the treatment of neovascular wet age-related macular degeneration (AMD). As part of the BLA filing, Genentech requested and has been granted a six-month Priority Review.
The FDA grants Priority Review to products that are considered to be potentially significant therapeutic advancements over existing approved therapies in the treatment, diagnosis or prevention of a disease. The FDA has six months from the submission date, or by the end of June 2006, to take action on the filing. The BLA was received by the FDA on December 30, 2005.
In addition, Genentech announced today that preliminary two-year data from the Phase III MARINA study showed that the improvement in the Lucentis groups at year one was maintained at year two as measured by visual acuity endpoints, while there was further deterioration of vision among patients in the control group. The difference between mean visual acuity in the Lucentis arms and the control arm increased at year two compared to year one. At least 90 percent of patients treated with Lucentis maintained (defined as a loss of less than 15 letters in visual acuity) or improved (defined as a gain of more than 15 letters in visual acuity) vision compared to approximately 53 percent of those treated in the control arm at year two [p0.0001].
"The FDA's decision to grant Priority Review underscores the potential significant advancement of Lucentis in the treatment of wet AMD and puts us one step closer to making available a therapy that may change outcomes for people with this devastating disease," said Hal Barron, M.D., Genentech's senior vice president of Development and chief medical officer. "The new two-year Phase III MARINA results provide us with additional important data from an ongoing rigorous clinical trial program that has consistently shown Lucentis improved or maintained vision for the majority of patients who otherwise may have faced blindness."
Consistent with year-one safety findings, common side effects that occurred more frequently in the Lucentis groups than in the control group at year two were mild to moderate and included conjunctival hemorrhage, increased intraocular pressure and vitreous floaters. Serious ocular adverse events in the MARINA study that occurred more frequently in the Lucentis-treated arms were uncommon and included endophthalmitis (cumulative 1.3 percent or less over two years) and intraocular inflammation (cumulative 1.7 percent or less over two years). Among non-ocular serious adverse events, the combined cumulative rate of cerebral vascular events and myocardial infarctions at two years was 3 percent (7/236) in the sham injection group, 4.6 percent (11/238) in the 0.3 mg Lucentis group and 4.2 percent (10/239) in the 0.5 mg group.
Genentech will submit two-year data from the Phase III MARINA study to the FDA. These data will be presented during the Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO) to be held in May 2006 in Fort Lauderdale, Fla.
The Genentech BLA submission for Lucentis was based on one-year clinical efficacy and safety data from two pivotal Phase III trials, ANCHOR and MARINA, as well as one-year clinical data from the Phase I/II FOCUS trial. Data from these studies demonstrate that Lucentis is the first investigational therapy to have improved vision in patients with wet AMD in two pivotal Phase III clinical trials. In addition, Lucentis is the first investigational therapy to have demonstrated a clinical benefit compared to verteporfin (Visudyne®) photodynamic therapy (PDT) in a head-to-head clinical study (ANCHOR).
MARINA (Minimally classic/occult trial of the Anti-VEGF antibody Ranibizumab In the treatment of Neovascular AMD) is a Phase III study of 716 patients in the United States with minimally classic or occult wet AMD who were randomized 2:1 to receive intravitreal Lucentis injections or a control regimen. The control regimen consisted of a sham injection, meaning the treating physician prepares and anesthetizes the patient's eye but does not perform an injection. Patients treated with Lucentis were further randomized to receive either a 0.3 mg or 0.5 mg dose of Lucentis once a month for two years. In October 2005, Genentech announced that patients in the sham arm of the MARINA study would be crossed over to active treatment with Lucentis.
In July 2005, Genentech presented positive preliminary one-year results from MARINA in which nearly 95 percent of patients treated with Lucentis maintained or improved vision at 12 months. Additional one-year results include:
Earlier this year, Genentech announced positive preliminary one-year Phase III data on Lucentis from ANCHOR, a study comparing two different doses of Lucentis to verteporfin (Visudyne®) photodynamic therapy (PDT) in 423 patients with predominantly classic wet 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 PDT. Data from the ANCHOR study also 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.
An analysis of 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).
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 were offered Lucentis for the remainder of the study.
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. The one-year study is 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.
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 1.7 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.
First Year Lucentis Safety Profile from Phase III Clinical Program
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 at one year). 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 at one year. 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).
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, Calif., 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 within the meaning of the Private Securities Litigation Reform Act of 1995 regarding Lucentis as a potential therapy. Actual results may differ materially. Among other things, Lucentis as a potential therapy could be affected by unexpected safety, efficacy or manufacturing issues, discussions with the FDA, FDA actions or delays, the failure to receive FDA approval, competition, pricing, reimbursement or the ability to supply product. 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.