Wednesday, Sep 7, 2005
South San Francisco, Calif. -- September 7, 2005 --Genentech, Inc. (NYSE: DNA) announced today plans to file a complete Biologics License Application (BLA) for the investigational drug Lucentis (ranibizumab) in December 2005. In addition, the company announced that it is in discussion with the U.S. Food and Drug Administration (FDA) regarding plans to initiate a Phase IIIb clinical study of Lucentis for patients with wet age-related macular degeneration (AMD). The study is anticipated to begin before the end of 2005. One-year Phase III data from the MARINA study presented at the annual meeting of the American Society of Retina Specialists in July showed Lucentis improved vision in patients with wet AMD.
"We recognize the significant unmet medical needs of those with wet AMD and hope to make Lucentis available to patients by seeking FDA approval as quickly as possible," said Hal Barron, M.D., Genentech senior vice president, development and chief medical officer. "We are encouraged by the magnitude of the benefit observed in the one-year Lucentis MARINA data and are excited about this new Phase IIIb trial, which will help provide more information about the safety profile of Lucentis and the treatment regimen for this chronic disease."
The Phase IIIb SAILOR (Safety Assessment of Intravitreal Lucentis for AMD) study is being designed to evaluate the safety of two different doses (0.3 mg and 0.5 mg) of Lucentis in a broad wet AMD population. Patients will receive Lucentis once a month for three months with criteria-based re-treatment options. Genentech anticipates that patients with wet AMD who have not received prior treatment for their disease or who continue to have active disease despite treatment with FDA-approved therapies may be eligible to enroll in SAILOR. The study will be conducted at more than 100 sites in the United States and enroll approximately 5,000 patients.
Genentech has also recently been notified that the FDA did not grant the company's request for fast-track designation, which allows for a rolling BLA submission. The FDA's decision will not affect the timing for BLA submission in December or the potential to obtain priority review for Lucentis.
Phase III MARINA Results
In July, Genentech announced positive preliminary Phase III data on Lucentis from a study of 716 patients with wet AMD. In addition to meeting the study's primary efficacy endpoint of maintaining vision in patients with wet AMD, 25 percent (59/238) of patients treated with 0.3 mg of Lucentis and 34 percent (81/240) treated with 0.5 mg of Lucentis improved vision by a gain of 15 letters or more compared to approximately 5 percent (11/238) of patients in the control group as measured by the Early Treatment of Diabetic Retinopathy (ETDRS) eye chart. Nearly 40 percent (188/478) of Lucentis-treated patients achieved a visual acuity score of 20/40 or better at 12 months compared to 11 percent (26/238) in the control group. At 12 months, patients treated with Lucentis gained an average of seven letters in visual acuity compared to study entry, while those in the control group lost an average of 10.5 letters.
An analysis of the one-year data showed that adverse events were similar to those seen in earlier trials of Lucentis. Common side effects occurring 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 uncommon (1 percent) and included uveitis and endophthalmitis. There appeared to be no imbalance in serious non-ocular adverse events.
Ongoing Phase III Studies
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 in patients 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. One-year results from this study are expected in the first half of 2006.
Genentech is enrolling 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 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 vision 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-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 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.