Wednesday, Oct 4, 2006
South San Francisco, Calif. -- October 4, 2006 --Genentech, Inc. (NYSE: DNA) announced today the publication of data from the two randomized, controlled pivotal Phase III clinical trials of LUCENTIS (ranibizumab injection) in the New England Journal of Medicine. The published findings include two-year efficacy and safety data from the MARINA trial and one-year efficacy and safety data from the ongoing ANCHOR trial. Based on these studies, LUCENTIS was granted U.S. Food and Drug Administration (FDA) approval on June 30, 2006 for the treatment of patients with the neovascular (wet) form of age-related macular degeneration (AMD), a leading cause of blindness in people over 55.
The MARINA and ANCHOR clinical trials met the primary efficacy endpoint of maintaining vision (defined as a loss of less than 15 letters in visual acuity) at one year in patients with wet AMD. In these studies, nearly all patients (approximately 95 percent) treated with LUCENTIS maintained or improved vision at one year compared with 62 percent of patients in the MARINA control group and 64 percent of patients in the ANCHOR control group. Importantly, up to 40 percent of patients experienced an improvement in vision of three lines (15 letters) or more on the study eye chart compared with 5 percent and 6 percent of patients in the MARINA and ANCHOR control groups, respectively. The improvement in visual acuity endpoints among patients treated with LUCENTIS in the MARINA study was maintained at year two, while patients in the control group continued to decline.
"The results of these Lucentis studies have changed the way we approach the treatment of wet AMD by demonstrating, for the first time, improvements in vision in more than one-third of patients treated,"said David Brown, M.D., lead author for the ANCHOR study and retina specialist at Vitreoretinal Consultants, The Methodist Hospital in Houston, Texas.
"What makes this publication particularly significant is that the visual acuity benefits after one year of treatment in the MARINA study were maintained through two years and associated with anatomic improvements consistent with the changes in visual acuity observed," said Philip J. Rosenfeld, M.D., Ph.D., professor of ophthalmology, Bascom Palmer Eye Institute in Miami and lead author for the MARINA study. "In this study, Lucentis had a favorable safety profile and did not appear to put patients at an additional risk for systemic adverse events and the ocular adverse event rates were similar to what we would expect among people in this age group who receive an injection in the eye."
Patients treated with LUCENTIS in these studies, on average, experienced an improvement over the control groups of three lines or more on the study eye chart. In both studies, up to 40 percent of patients treated with LUCENTIS achieved vision of 20/40 or better at one year compared with 11 percent of patients in the MARINA control group and 3 percent of patients in the ANCHOR control group. At two years, 42 percent of patients treated with LUCENTIS in the MARINA study achieved vision of 20/40 or better compared with 6 percent of patients in the control group. Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart, the standard method of quantifying visual acuity.
"The publication of these two studies represents nearly a decade of rigorous clinical study of Lucentis that has led to a new era in the treatment of wet AMD,"said Hal Barron, M.D., Genentech senior vice president, Development and chief medical officer. "We have already begun to expand on the findings of these studies to better understand optimal treatment regimens for patients with wet AMD, as well as explore the potential for Lucentis to meet other unmet medical needs in ophthalmology."
LUCENTIS was specifically developed for intraocular use in the eye to treat the underlying cause of wet AMD by targeting the molecular pathway that controls the formation of new blood vessels. LUCENTIS is 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 0.5 mg is recommended for intravitreal injection once a month. If monthly injections are not feasible, treatments can be reduced to one injection every three months after the first four monthly injections. Compared to continued monthly dosing, dosing every three months will lead to an approximate five-letter (one-line) loss of visual acuity benefit, on average, over the following nine months. Patients should be evaluated regularly.
Caption: Mean change in visual acuity over time for the Phase III MARINA ("Study 1) and the Phase III ANCHOR ("Study 2) studies of LUCENTIS (ranibizumab injection).
About the Pivotal Studies
MARINA (Minimally classic/occult trial of the Anti-VEGF antibody Ranibizumab In the treatment of Neovascular AMD) was a Phase III randomized, multi-center, double-masked, sham-controlled study of 716 patients in the United States with minimally classic or occult wet AMD who were randomized 1:1:1 to receive intravitreal LUCENTIS injections (0.3 mg or 0.5 mg) or a control regimen once a month for two years. 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.
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 verteporfin (Visudyne®) photodynamic therapy (PDT) in 423 patients with predominantly classic wet AMD in the United States, Europe and Australia. Patients were randomized 1:1:1 to receive intravitreal LUCENTIS injections (0.3 mg or 0.5 mg) once a month or PDT every three months for two years.
LUCENTIS Safety Profile
In clinical trials, the most common adverse reactions among patients treated with LUCENTIS (reported in at least 6 percent more patients than in the control groups in at least one study) included conjunctival hemorrhage, eye pain, vitreous floaters, increased intraocular pressure and intraocular inflammation. Although there was a low rate (less than 4 percent) of arterial thromboembolic events (ATEs) observed in the LUCENTIS clinical trials that was not statistically different between the LUCENTIS and control groups, there is a theoretical risk of ATEs following intravitreal use of inhibitors of VEGF. Serious adverse events related to the injection procedure occurred in less than 0.1 percent of intravitreal injections, including endophthalmitis, retinal detachments and traumatic cataracts. Other serious ocular adverse events observed among LUCENTIS-treated patients (that occurred in less than 2 percent of patients) included intraocular inflammation and increased intraocular pressure. LUCENTIS is contraindicated in patients with hypersensitivity and ocular or periocular infections.
LUCENTIS (ranibizumab injection) (0.5 mg) is approved for the treatment of patients with neovascular (wet) AMD. LUCENTIS is a recombinant humanized IgG1 kappa isotype therapeutic antibody fragment developed for intraocular use. LUCENTIS binds to and inhibits the biologic activity of human 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). VEGF-A has been shown to lead to wet AMD disease progression and central vision loss. LUCENTIS was 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 Novartis has exclusive commercial rights for the rest of the world. For LUCENTIS prescribing information, please call 1-866-LUCENTIS or visit http://www.lucentis.com.
AMD is a major cause of painless central vision loss and is a leading cause of blindness in people over 55. The National Eye Institute estimates that there are 1.7 million people with the advanced form of 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 process 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's Commitment to Patient Access
Genentech is committed to assisting eligible patients in accessing our therapies for approved indications, regardless of their ability to pay. Although Genentech's products are covered by most government and private insurance, Genentech established the Genentech® Access to Care Foundation (GATCF) in 1990 for its marketed products, and donates free product to eligible uninsured patients in the United States, except for Pulmozyme® (dornase alfa, recombinant), which is covered by the Genentech Endowment for Cystic Fibrosis. In 2005 alone, GATCF supported over 18,000 patients by providing approximately $200 million of free product. Genentech recently donated more than $25 million to several independent public charities that provide financial assistance to eligible patients who cannot access needed medical treatment due to co-pay costs. To learn more about these independent, public charities and potential financial assistance options, patients can speak with an Alternative Funding Specialist from Genentech's Single Point of Contact (SPOC) group by calling 866-724-9394 or visiting http://www.SPOConline.com.
Founded 30 years ago, 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 a forward-looking statement regarding the potential for Lucentis to meet other unmet medical needs in ophthalmology. Such statement is a prediction and involves risks and uncertainties such that the actual result may differ materially. Among other things, Lucentis' potential could be affected by unexpected safety, efficacy or manufacturing issues, need for additional clinical studies, discussions with the FDA or FDA actions, failure to receive or maintain FDA approval, competition, reimbursement or coverage, pricing, the ability to supply product, product withdrawal, new product approvals and launches, intellectual property or contract rights, and achieving sales revenue consistent with internal forecasts. 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 statement in this press release.