Biogen Idec And Genentech Submit A Supplemental Biologics License Application For FDA Review Of Rituxan For The Treatment Of Rheumatoid Arthritis

August 31, 2005 -- Biogen Idec, Inc. and Genentech, Inc. announced today that the companies submitted a supplemental Biologics License Application (sBLA) with the U.S. Food and Drug Administration (FDA) for a new indication for Rituxan� (Rituximab) in patients with active rheumatoid arthritis (RA) who inadequately respond to an anti-TNF therapy. The sBLA submission is based primarily on the 24-week results of a multi-center, randomized, double-blind, placebo-controlled Phase III study known as REFLEX. In the trial, patients who received a single course of two infusions of Rituxan with a stable dose of methotrexate (MTX) displayed a statistically significant improvement in symptoms measured at 24 weeks, compared to those receiving placebo and MTX. "We are pleased to be submitting these Rituxan RA data to the FDA and will work closely with the Agency throughout the review process," said Burt Adelman, M.D., executive vice president, development, Biogen Idec. "Rituxan may provide a potential new treatment approach for the RA patient population with the greatest unmet medical need," said Hal Barron, M. D., Genentech's senior vice president, development and chief medical officer. "This submission marks an important milestone in our ongoing efforts to develop novel therapies for B-cell-mediated diseases." The most common side effects in the Rituxan arm of REFLEX included headache, upper respiratory tract infection and nasopharyngitis. The reported rate of serious adverse events was comparable across treatment arms. Analysis of the REFLEX 24-week data did not reveal any unexpected safety signals, and the companies continue to monitor the long-term safety of Rituxan in all clinical trials. The results of the REFLEX trial will be presented at the American College of Rheumatology meeting in San Diego in November. About Rheumatoid Arthritis RA is a debilitating autoimmune disease that affects more than two million Americans1 and hinders the daily activities of sufferers. RA occurs when the immune system inappropriately attacks joint tissue, causing painful chronic inflammation and irreversible destruction of cartilage, tendons and bones, often resulting in disability. While RA has traditionally been considered a T-cell-mediated disease, emerging research suggests that other immune cells called B-cells may play multiple roles in the pathophysiology of RA, including autoantibody production, T-cell activation and cytokine production. Common RA symptoms include inflammation of the joints, swelling, fatigue, stiffness and pain. Additionally, since RA is a systemic disease, it can have effects in other tissues such as the lungs, eyes and bone marrow. About Rituxan Rituxan is a therapeutic antibody that targets and selectively depletes CD-20-positive B- cells without targeting stem cells or existing plasma cells. Rituxan is also being investigated in other autoimmune diseases, including lupus, multiple sclerosis and ANCA-associated vasculitis. Rituxan, discovered by Biogen Idec, received FDA approval in November 1997 for the treatment of relapsed or refractory low-grade or follicular, CD-20-positive, B-cell non-Hodgkin?s lymphoma (NHL). Recently, Genentech and Biogen Idec submitted a regulatory filing for FDA review of Rituxan for front-line treatment of intermediate grade or aggressive CD-20-positive B-cell NHL. It also was approved in the European Union under the trade name MabThera� in June 1998. Genentech and Biogen Idec co-market Rituxan in the United States, and Roche markets MabThera in the rest of the world, except Japan, where Rituxan is co-marketed with Zenyaku Kogyo Co. Ltd. Rituxan has been used to treat more than 730,000 patients worldwide. For a copy of the Rituxan full prescribing information, including Boxed Warning, please call 1-800-821-8590 or visit http://www.gene.com. Rituxan Safety Profile in NHL In NHL patients, the majority of patients experience infusion-related symptoms with their first Rituxan infusion. These symptoms include but are not limited to: flu-like fever, chills/rigors, nausea, urticaria, headache, bronchospasm, angioedema and hypotension. These symptoms vary in severity and generally are reversible with medical intervention. In rare instances, severe and fatal infusion-related reactions have occurred, nearly all of which have been associated with the first Rituxan infusion. These events appear as manifestations of an infusion-related complex and include hypoxia, pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, cardiogenic shock and tumor lysis syndrome. Patients who develop clinically significant infusion-related cardiopulmonary events should have their Rituxan infusion discontinued and receive medical treatment. In rare instances, severe mucocutaneous skin reactions have occurred that may be associated with Rituxan therapy. Many of these reactions have been described as paraneoplastic pemphigus and are known to be associated with various B-cell lymphomas, particularly NHL and chronic lymphocytic leukemia. Patients who develop a severe mucocutaneous skin reaction should have Rituxan discontinued and receive appropriate medical treatment, including a skin biopsy to guide therapy. Source: Genentech Press Release

South Korea Unveils First Dog Clone August 2005. Scientists in South Korea have produced the first dog clones, they report in Nature magazine this week. One of the puppies died soon after birth but the other, an Afghan hound named Snuppy, is still doing well after 16 weeks, the researchers say. Snuppy joins a host of other cloned animals including Dolly the sheep, CC the cat and Ralph the rat. Scientists hope dog clones will help them understand and treat a range of serious human diseases. The overall objective of this program is to learn about the root causes of diseases. "The dog has characteristics similar to human beings," said lead researcher Woo Suk Hwang of Seoul National University, South Korea. "Some of their diseases are almost the same as human diseases. "So [dog clones] could be very valuable in finding technologies useful for curing human diseases. This is our main research call." Snuppy, whose name stands for Seoul National University puppy, was made from a cell taken from the ear of a three-year-old male Afghan hound. Scientists took the genetic material from the ear cell and placed it into an empty egg cell. This egg was then stimulated to start dividing and develop into an embryo. Once growing, it was transferred to Snuppy's surrogate mother, a yellow labrador. The Afghan pup was born by caesarian section after a full 60 days of pregnancy. Although many other animals have been successfully cloned, dogs are notoriously difficult: the South Korean team only obtained three pregnancies from more than 1,000 embryo transfers into 123 recipients. Of these, one miscarried and one died soon after birth; only Snuppy remains. The hairy puppy, like other cloned animals, is generating a flurry of interest around the world. Some people are concerned about the ethical implications of this research. No one can deny that techniques that advance our understanding of diseases and their therapy are to be encouraged. But cloning of animals raises many ethical and moral issues that have still to be properly debated within the profession.

Preliminary Phase I/II Data Show Lucentis In Combination With Visudyne Maintained Or Improved Vision In Approximately 90 Percent Of Patients With Wet Age-Related Macular Degeneration

South San Francisco, Calif. -- May 31, 2005. Genentech, Inc. announced today that a single-masked Phase I/II clinical study of the investigational drug Lucentis™ (ranibizumab) met its primary efficacy endpoint of maintaining vision in patients with wet age-related macular degeneration (AMD) when used in combination with verteporfin (Visudyne®) photodynamic therapy (PDT). Approximately 90 percent of patients maintained or improved vision (defined as a loss of less than 15 letters in visual acuity) when treated with the combination of Lucentis and PDT compared to approximately 68 percent of those treated in the control arm of PDT alone (p = 0.0003). Patients treated with Lucentis plus PDT at 12 months had, on average, a significant improvement in visual acuity compared to visual acuity at study entry, an important secondary endpoint, while the PDT-alone group demonstrated a decrease in mean visual acuity from baseline to 12 months. One-year data from the trial will be presented at the 23rd Annual Meeting of the American Society of Retina Specialists (ASRS), July 16 to 20 in Montreal, Canada. A preliminary analysis of the data showed there was an increased risk of the serious ocular adverse event uveitis in patients treated with Lucentis in combination with PDT compared to patients treated with PDT alone. An amendment to the study protocol was made after data safety monitoring identified this imbalance. After uveitis, endophthalmitis was the second most common ocular serious adverse event occurring in patients treated with Lucentis. Among non-ocular serious adverse events, the frequency of cerebral vascular events was slightly higher in those treated with Lucentis, while the frequency of myocardial infarctions was slightly higher in the PDT-alone arm. In both cases, the difference between groups was not statistically significant. "We are excited to see a statistically significant improvement in vision for patients with wet AMD in a second trial in which patients were treated with Lucentis," said Hal Barron, M.D., Genentech's senior vice president, development and chief medical officer. Genentech and Novartis Pharma AG recently announced top-line positive results from the Phase III MARINA study. A preliminary analysis of the MARINA data showed that adverse events were similar to those seen in earlier trials of Lucentis. Common side effects occurring in the Lucentis arms more frequently 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 rare (<1%) and included uveitis and endophthalmitis. There appeared to be no imbalance in serious non-ocular adverse events in the MARINA study. Lucentis is a humanized therapeutic antibody fragment developed at Genentech and designed to bind and inhibit Vascular Endothelial Growth Factor A (VEGF-A), a protein that plays a critical role in angiogenesis (the formation of new blood vessels). About the Study The FOCUS (RhuFab V2 Ocular Treatment Combining the Use of Visudyne™ to Evaluate Safety) trial is a Phase I/II randomized, single-masked study evaluating the safety, tolerability and efficacy of Lucentis in combination with PDT in 162 patients with predominantly classic subfoveal wet AMD. In this study, patients were randomized 2:1 to receive PDT followed by either 0.5 mg injections of Lucentis or sham injections for 23 months. To perform a sham injection, the treating physician prepares and anesthetizes the patient's eye but does not perform an injection. The FOCUS study was conducted at 25 sites in the United States. Ongoing Phase III Studies The MARINA (Minimally classic/ occult trial of the Anti-VEGF antibody RhuFab V2 In the treatment of Neovascular AMD) study is a randomized, 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 subfoveal wet AMD. 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 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. Results from this study are expected in the first half of 2006. About Lucentis Lucentis (ranibizumab) is a humanized therapeutic antibody fragment developed at Genentech and designed to bind and inhibit VEGF-A, a protein that plays 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. About Age-related Macular Degeneration 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. 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. About Angiogenesis 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 protein plays 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. The statements made in this press release relating to the expected time frame for results from the Phase III ANCHOR and PIER trials are forward-looking and actual results could differ materially. Among other things, the timing could be affected by additional time requirements for data analysis or discussions with the FDA. Source: Genentech Press Release

OSI Pharmaceuticals And Genentech Announce Filing Of A Supplemental New Drug Application To The FDA For Tarceva In Pancreatic Cancer

May 2005. Volume 9. Melville, N.Y. And South San Francisco, Calif. -- May 2, 2005 -- OSI Pharmaceuticals, Inc. and Genentech, Inc. announced that OSI submitted a supplemental New Drug Application (sNDA) with the U.S. Food and Drug Administration (FDA) for use of Tarceva™ (erlotinib) plus gemcitabine chemotherapy for the treatment of advanced pancreatic cancer in patients who have not received any previous treatment. Tarceva is the first drug to significantly improve survival in a Phase III trial when added to gemcitabine chemotherapy in first-line pancreatic cancer compared to gemcitabine alone. "There is an urgent need for additional therapeutic options for patients with advanced pancreatic cancer and we look forward to working closely with the FDA through this review process," stated Colin Goddard, Ph.D., Chief Executive Officer of OSI Pharmaceuticals. "Pancreatic cancer is difficult to treat and is a disease in which only 20 percent of patients survive one year after diagnosis. The improved survival observed in the Phase III trial that is the basis for this filing represents a potential treatment advance for both patients and physicians," said Hal Barron, M.D., Genentech's senior vice president of Development and chief medical officer. "We would like to recognize our colleagues at OSI Pharmaceuticals for their hard work on this important filing." The sNDA filing is based on a pivotal Phase III multi-center, randomized, double-blind, placebo-controlled trial evaluating Tarceva in patients with locally advanced or metastatic pancreatic cancer. Results of the trial were presented in January at the Second Annual Gastrointestinal Cancers Symposium in Hollywood, Fla. A total of 569 patients were randomized in the study, to receive Tarceva plus gemcitabine or gemcitabine plus placebo. The study demonstrated a statistically significant 23.5 percent improvement in overall survival for patients receiving Tarceva plus gemcitabine compared to patients receiving gemcitabine plus placebo. Twenty-four percent of patients receiving Tarceva plus gemcitabine were alive after one year compared to 17 percent of patients receiving gemcitabine plus placebo. Median survival in the Tarceva plus gemcitabine arm was 6.4 months compared to 5.9 months in the gemcitabine plus placebo arm. An exploratory analysis of survival by pre-treatment characteristics also showed that patients with metastatic disease and patients with poor performance status derived a significant survival benefit. Progression-free survival in the Tarceva plus gemcitabine arm also was significantly improved, although there was virtually no difference in tumor response (9 percent in patients receiving Tarceva plus gemcitabine versus 8 percent in the gemcitabine plus placebo arm). The analysis of safety data did not reveal any unexpected safety signals beyond that seen in previous studies of Tarceva in both monotherapy and combination settings. As expected, rash and diarrhea were the principal Tarceva related side effects seen in the study. Rash was reported by 72 percent of patients who received Tarceva plus gemcitabine and by 28 percent of patients who received gemcitabine plus placebo. Diarrhea was reported by 51 percent of patients who received Tarceva plus gemcitabine and by 36 percent of patients who received gemcitabine plus placebo. Possible interstitial lung disease (ILD) was experienced by 2.1 percent of patients in the Tarceva plus gemcitabine arm compared with 0.4 percent in the gemcitabine plus placebo arm. These ILD incidence levels for the combination of Tarceva and gemcitabine were higher than the 0.8 percent incidence reported for both monotherapy Tarceva and placebo in the pivotal BR.21 study in advanced NSCLC. However, the incidence of possible ILD from all clinical studies with Tarceva is 0.7 percent. About Pancreatic Cancer According to the World Health Organization, more than 216,000 people worldwide are diagnosed each year with pancreatic cancer. The American Cancer Society estimates that in 2005 approximately 32,180 people in the United States will be diagnosed with pancreatic cancer and approximately 31,800 will die of the disease. Most pancreatic tumors originate in the exocrine duct cells or in the cells that produce digestive enzymes (acinar cells). Called adenocarcinomas, these tumors account for nearly 95 percent of pancreatic cancers. About Tarceva Tarceva is currently approved by the FDA as a monotherapy for the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen and is an oral tablet indicated for daily administration. Results from two earlier large, randomized, placebo-controlled clinical trials in first-line advanced NSCLC patients showed no clinical benefit with concurrent administration of Tarceva with doublet platinum-based chemotherapy (carboplatin and paclitaxel or gemcitabine and cisplatin) and its use is not recommended in that setting. Tarceva is a small molecule designed to target the human epidermal growth factor receptor 1 (HER1) pathway, which is one of the factors critical to cell growth in a number of different cancer types. HER1, also known as EGFR, is a component of the HER signaling pathway, which plays a role in the formation and growth of numerous cancers. Tarceva is designed to inhibit the tyrosine kinase activity of the HER1 signaling pathway inside the cell, which may block tumor cell growth. Tarceva is the only EGFR therapy to show in a Phase III trial improved survival for advanced NSCLC patients. Additional early-stage trials of Tarceva are being conducted in other solid tumors. About Tarceva Safety In the pivotal NSCLC trial, the most common adverse reactions in patients receiving Tarceva were rash and diarrhea. Severe grade 3/4 rash and diarrhea occurred in nine and six percent of Tarceva-treated patients, respectively. Rash and diarrhea each resulted in discontinuation of one percent of Tarceva-treated patients. Dose reduction was needed for six and one percent of patients for rash and diarrhea, respectively. Historically, there have been infrequent reports of serious interstitial lung disease (ILD), including fatalities, in patients receiving Tarceva for treatment of NSCLC or other advanced solid tumors. In the Phase III trial, severe pulmonary reactions, including potential cases of interstitial lung disease, were infrequent (0.8 percent) and were equally distributed between treatment arms. The overall incidence of possible ILD in Tarceva-treated patients from all studies was approximately 0.7 percent. SOURCE: Genentech Press Release

Genentech And Ipsen Agree To Develop Sustained-Release Formulations Of Recombinant Human Growth Hormone

South San Francisco, Calif. and Paris -- March 21, 2005 -- Genentech, Inc and Ipsen today announced the recent execution of a collaborative research and development (R&D) agreement to develop sustained-release formulations of Genentech's recombinant human growth hormone [somatropin (rDNA origin)]. This R&D collaboration is in addition to and supplements a previous agreement signed in 2002 whereby Ipsen gained exclusive rights to market NutropinAq™ Pen throughout Europe and the rest of the world, excluding North America and Japan. Nutropin AQ Pen® for use with the Nutropin AQ Pen® cartridge was cleared for marketing by the U.S. Food and Drug Administration in April 2002 and obtained marketing authorization under the trade name NutropinAq Pen from the European Medicines Agency in March 2004. Ipsen has already launched NutropinAq Pen in 12 European countries. "We at Ipsen are proud to bring our expertise in sustained-release technology to this new collaboration with Genentech," said Mr. Jean-Luc Belingard, president and chief executive officer of the Ipsen Group. "Our common objective is to develop sustained-release formulations of recombinant human growth hormone to meet the needs of pediatric and adult growth hormone deficiency (GHD) patients." About Nutropin AQ Nutropin AQ [somatropin (rDNA origin) injection] is produced using recombinant DNA technology and has the same amino acid sequence as human growth hormone produced naturally in the human body. It is marketed as NutropinAq in Austria, Denmark, Finland, France, Germany, Ireland, the Netherlands, Norway, Sweden, Portugal, Spain and the United Kingdom. Other regulatory reviews are underway in Europe and worldwide, excluding North America and Japan. Nutropin AQ is supplied as 10 mg of sterile liquid somatropin per cartridge for exclusive use with the Nutropin AQ Pen, a simple, convenient, easy-to-use device for subcutaneous injection. Nutropin AQ is approved for the treatment of GHD in children and adults, for the long-term treatment of short stature in children with Turner syndrome and the treatment of growth failure in chronic renal insufficiency patients prior to transplantation. Nutropin AQ Safety Information Growth hormone should not be initiated to treat patients with acute critical illness due to complications following open heart or abdominal surgery, multiple accidental trauma, or to patients having acute respiratory failure. Nutropin AQ should not be used for growth promotion in pediatric patients with closed epiphyses. Nutropin AQ should not be used in patients with active neoplasia. Growth hormone therapy should be discontinued if evidence of neoplasia develops. Growth hormone is contraindicated in patients with Prader-Willi syndrome who are severely obese or have severe respiratory impairment. Unless patients with Prader-Willi syndrome also have a diagnosis of growth hormone deficiency, Nutropin AQ is not indicated for the long-term treatment of pediatric patients who have growth failure due to genetically confirmed Prader-Willi syndrome. Source: Genentech Press Release

Three-Year Study With Raptiva Showed Long-Term And Sustained Clearing In Moderate-To-Severe Plaque Psoriasis Patients

February 18, 2005 -- Genentech, Inc. presented final results from a long-term study that showed sustained improvement in psoriasis symptoms throughout three years of continuous treatment with RAPTIVA® (efalizumab). This three-year study is the longest study of psoriasis patients receiving continuous treatment with a biologic agent. "RAPTIVA is the first biologic therapy to show sustained benefit for psoriasis patients treated continuously over a three-year period," said Craig Leonardi, M.D., associate clinical professor of dermatology at St. Louis University Medical School, St. Louis, Mo., and a study investigator. "Given that psoriasis is a chronic disease, as dermatologists we must weigh the efficacy and safety of different treatment options over the long term. It is encouraging to see a consistent safety profile for RAPTIVA in this three-year open-label study." The 36-month, Phase IIIb open-label study evaluated the long-term safety and efficacy of continuous treatment with RAPTIVA in adults with moderate-to-severe chronic plaque psoriasis. The results were presented as a poster at the American Association of Dermatology ACADEMY 2005 meeting in New Orleans. Key Study Findings: At 33 months, of the 151 patients who remained in the study and continued to receive weekly RAPTIVA therapy: * 75 percent (113/151) of patients showed a 75 percent or greater improvement on the Psoriasis Area Severity Index (PASI 75) * 41 percent of patients (62/151) showed a 90 percent or greater PASI improvement (PASI 90). At the end of the final three-month transitional period of the three-year study (at 36 months), of the 113 patients who continued in the study and received weekly RAPTIVA therapy: * 73 percent (82/113) of patients showed a 75 percent or greater PASI improvement (PASI 75) * 40 percent of patients (45/113) showed a 90 percent or greater PASI improvement (PASI 90). An analysis of a small number of patients using concomitant systemic therapies demonstrated that the addition of these agents did not have a significant effect on patient response rates. Study Design In this study, 339 patients received RAPTIVA weekly for an initial 12 weeks, and patients with a PASI 50 response or a static Physician’s Global Assessment response of ‘mild’ or better after 12 weeks of treatment were eligible to continue on a once-weekly maintenance dose of 1mg/kg RAPTIVA for 12-week periods starting at week 13. A total of 290 subjects entered this second phase of the study. For each successive three-month period of treatment, dropouts during that period were analyzed using their last available PASI assessment but were excluded from the subsequent cohorts. Adverse events in this study were similar to what has been observed in previous clinical trials of RAPTIVA and include headache, non-specific infection (e.g., common colds), chills, pain, nausea, asthenia (weakness), and fever, all of which diminished after the first 1-2 doses. Further, there was no evidence of accumulation or cumulative toxicity. During the final six months of the study, the occurrence of serious adverse events was low and consistent with data from previous RAPTIVA Phase III studies. About RAPTIVA RAPTIVA® (efalizumab) is a humanized therapeutic antibody designed to selectively and reversibly block the activation, reactivation and trafficking of T-cells that lead to the development of psoriasis. In October 2003, RAPTIVA received U.S. Food and Drug Administration approval for the treatment of chronic moderate-to-severe plaque psoriasis in adults 18 years or older who are candidates for systemic therapy or phototherapy. The recommended dose of RAPTIVA is a single 0.7 mg/kg SC conditioning dose followed by weekly SC doses of 1 mg/kg. RAPTIVA can be self-administered by patients as a single, once-weekly, subcutaneous injection after proper training by a healthcare professional. In clinical studies, RAPTIVA demonstrated a rapid onset of action in the reductions of symptoms associated with psoriasis, in some patients within four weeks of initial treatment. More than 3,500 patients in the United States and Europe have been included in RAPTIVA trials to date, creating the largest existing database of patients taking part in studies with a biological therapy for psoriasis. Serono S.A., Genentech's partner outside the United States and Japan recently announced that it has received approval for RAPTIVA in a total of 33 countries, including those of the European Union, Switzerland, Australia, Argentina, Mexico and Brazil. European Commission approval was received in late September following a unanimous positive opinion from 25 countries of the the Committee of Medicinal Products for Human Use (CHMP) recommending approval. Serono announced earlier this month that RAPTIVA is now available in 15 countries in its territories. It is awaiting the outcomes of marketing applications in a number of other counties in the territories for which it is responsible. Important Safety Information Common adverse events that occurred at least two percent more frequently in RAPTIVA patients than in placebo included headache, infection (mostly upper respiratory infections), chills, nausea, pain, myalgia (muscle pain), flu syndrome, fever, back pain, and acne. Five of these events (headache, chills, fever, nausea and myalgia) were predominantly acute adverse events and were principally seen following the first two injections of RAPTIVA. For the third and subsequent doses, the incidence of acute adverse events was similar between the RAPTIVA and placebo groups. Less than one percent of patients were discontinued from treatment due to acute adverse events. RAPTIVA is an immunosuppressive agent and has the potential to increase the risk of infection and reactivate latent, chronic infections. Many immunosuppressive agents have the potential to increase the risk of malignancy. The role of RAPTIVA in the development of malignancies is not known. Serious adverse events occurring in clinical studies with RAPTIVA were serious infections (0.4% in RAPTIVA vs. 0.1% in placebo), malignancy (the overall incidence of malignancies of any kind was 1.8 per 100 patient-years for RAPTIVA-treated patients compared with 1.6 per 100 patient-years for placebo-treated patients), thrombocytopenia (0.3% RAPTIVA vs. 0.0% placebo), and worsening of psoriasis, typically upon discontinuation (0.7% in RAPTIVA vs. 0.0% in placebo). About Psoriasis Psoriasis occurs when new skin cells grow abnormally, resulting in thick, red, scaly, inflamed patches. Plaque psoriasis, the most common form of the disease, affects approximately 2.3 million Americans and is characterized by inflamed patches of skin ("lesions") topped with silvery white scales. Psoriasis can be limited to a few spots or involve extensive areas of the body, appearing most commonly on the scalp, knees, elbows and trunk. Although it is highly visible, psoriasis is not a contagious disease. While there are a number of medications that may help control the symptoms of psoriasis, there currently is no known cure. Source: Genentech Press Release

Randomized Phase III study-E3200 of Avastin™ (bevacizumab) plus the FOLFOX4 chemotherapy regimen (oxaliplatin/5-FU/leucovorin)

Preliminary Positive Results From Phase III Trial Of Avastin Plus FOLFOX4 Chemotherapy Presented At ASCO GI Meeting January 27, 2005 -- Genentech, Inc. announced that a randomized Phase III study (E3200) of Avastin™ (bevacizumab) plus the FOLFOX4 chemotherapy regimen (oxaliplatin/5-FU/leucovorin), compared to FOLFOX4 alone in second-line metastatic colorectal cancer patients achieved its primary endpoint of improving overall survival. These data, first announced by the National Cancer Institute (NCI) and Genentech in November 2004, were presented by Bruce J. Giantonio, M.D., of the Abramson Cancer Center at the University of Pennsylvania in Philadelphia at the Second Annual Gastrointestinal Cancers Symposium. Avastin is currently approved as a first-line treatment for metastatic colorectal cancer in combination with intravenous 5-FU-based chemotherapy. Results from a preliminary analysis of the E3200 study demonstrated that patients receiving Avastin plus FOLFOX4 had a 26 percent reduction in the risk of death (a hazard ratio of 0.74), the primary endpoint, compared to patients who received FOLFOX4 alone. Median survival for patients receiving Avastin plus FOLFOX4 was 12.5 months, compared to 10.7 months for those receiving FOLFOX4 alone, a 17 percent improvement. "Avastin is the only targeted therapy to demonstrate an improvement in survival in first-line metastatic colorectal cancer patients, who on average face a two-year life expectancy upon diagnosis. The data presented today show that Avastin in combination with the FOLFOX4 regimen may be an effective treatment for second-line metastatic colorectal cancer," said Gwen Fyfe, M.D., Genentech's vice president, Clinical Hematology/Oncology. "The results from this study add to the growing body of data showing that the addition of Avastin to 5-FU-based chemotherapy regimens can result in meaningful clinical benefit to patients with metastatic colorectal cancer, and we have initiated discussions with the FDA to determine a filing strategy for the use of Avastin plus FOLFOX in the second-line population." Adverse events in this Phase III study were consistent with those seen in previous Avastin and FOLFOX4 clinical trials in metastatic colorectal cancer. The most frequent adverse events were hypertension and sensory neuropathy, with six percent of patients (17/286) in the Avastin plus FOLFOX4 arm experiencing Grade 3 or 4 hypertension compared to two percent (5/282) in the FOLFOX4 arm. Grade 3 and 4 sensory neuropathy occurred at a rate of 15 percent (44/286) in the Avastin plus FOLFOX4 arm, compared to a rate of nine percent (26/282) in the FOLFOX4 arm. The most serious adverse events were bleeding, which occurred at a rate of 2.8 percent (8/286) in the Avastin + FOLFOX4 arm and less than one percent (1/282) in the FOLFOX4 arm, gastrointestinal perforation, which occurred at a rate of one percent (3/286) in the Avastin plus FOLFOX4 arm, and thrombosis, which occurred in 4.5 percent of patients (13/286) treated with Avastin plus FOLFOX4 and compared to 2.8 percent of patients (8/282) treated with FOLFOX4. About the E3200 Study This Phase III study was a randomized, controlled, multicenter trial that enrolled 829 patients with advanced colorectal cancer who had previously received a 5-FU-based therapy and irinotecan, either alone or concurrently, for advanced disease or if their disease had relapsed within six months of concluding adjuvant treatment with these chemotherapy agents. The patients enrolled in this trial were randomized to receive treatment with the FOLFOX4 regimen with or without Avastin. Randomization to a third arm of the study evaluating single-agent Avastin was suspended in March 2003 on the recommendation of the Data Monitoring Committee overseeing the study when review of early results suggested that overall survival for patients in that group might be lower compared to that of patients treated in the other two arms. Results from this treatment arm have not yet been disclosed. The trial was sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health, and conducted by a network of researchers led by the Eastern Cooperative Oncology Group (ECOG). Genentech provided Avastin for the trial under the Cooperative Research and Development Agreement (CRADA) with the NCI for the clinical development of Avastin. About Avastin Avastin is a therapeutic antibody designed to inhibit Vascular Endothelial Growth Factor (VEGF), a protein that plays an important role in tumor angiogenesis and maintenance of existing tumor vessels. By binding to VEGF, Avastin is designed to interfere with the blood supply to tumors, a process that is critical to tumor growth and metastasis. For full prescribing information, including Boxed Warnings for Avastin and information about Avastin and angiogenesis, visit www.gene.com or www.avastin.com. The FDA approved Avastin on February 26, 2004 as a first-line treatment for metastatic colorectal cancer in combination with intravenous 5-FU-based chemotherapy. Approval was based on data from two trials. The pivotal trial was a large, placebo-controlled, randomized study of 925 patients that demonstrated a prolongation in the median survival of patients treated with Avastin plus the IFL (5-FU/leucovorin/CPT-11) chemotherapy regimen by approximately five months, compared to patients treated with the IFL chemotherapy regimen alone (20.3 months versus 15.6 months). In addition, this study demonstrated an improvement in progression-free survival (PFS) of more than four months (10.6 months in the Avastin/IFL arm compared to 6.4 months in the IFL-alone arm). The survival and PFS results observed when Avastin is added to first-line chemotherapy are the longest ever reported in a randomized, Phase III study of patients with metastatic colorectal cancer. Last year the National Comprehensive Cancer Network (NCCN), an alliance of 19 of the world's leading cancer centers, updated their Colorectal Clinical Practice Guidelines and added Avastin in combination with 5-Fluorouracil-based regimens -- including those using oxaliplatin or irinotecan -- to its list of treatment options for first-line advanced colon or rectal cancer. Based on data showing that VEGF may play a broad role in a range of cancers, Genentech is pursuing a late-stage clinical development program with Avastin evaluating its potential use in adjuvant and metastatic colorectal, renal cell (kidney), breast and non-small cell lung cancers. Avastin is also being evaluated in earlier stage trials as a potential therapy in prostate, ovarian, and several types of solid tumor cancers and hematologic malignancies and melanoma. Avastin Safety Profile Avastin has a well-established safety profile. In Genentech-sponsored studies, the most serious adverse events associated with Avastin were infrequent, and included gastrointestinal perforation, wound healing complications, hemorrhage, arterial thromboembolic events, hypertensive crisis, nephrotic syndrome and congestive heart failure. The most common Grade 3-4 adverse events (occurring in greater than two percent of patients in the Avastin arm, compared to the control group) were asthenia, pain, hypertension, diarrhea and leukopenia. The most common adverse events (occurring in greater than two percent of patients in the Avastin arm, compared to the control group) of any severity were asthenia, pain, abdominal pain, headache, hypertension, diarrhea, nausea, vomiting, anorexia, stomatitis, constipation, upper respiratory infection, epistaxis, dyspnea, exfoliative dermatitis and proteinuria. About VEGF and Tumor Angiogenesis The link between angiogenesis and cancer growth has been discussed by many researchers for decades. It wasn't until 1989 that a key growth factor influencing the process, VEGF, was discovered by Napoleone Ferrara, M.D., a staff scientist at Genentech. Dr. Ferrara and his team cloned VEGF, providing some of the first evidence that a specific angiogenic growth factor existed. This research was published in the journal Science in 1989. Dr. Ferrara then created a mouse antibody to this protein. In 1993, Dr. Ferrara and his team at Genentech, in a study published in Nature, demonstrated that the antibody directed against VEGF could suppress angiogenesis and tumor growth in preclinical models, providing compelling evidence that VEGF can play a critical role in tumor growth. Clinical studies with a humanized version of the antibody, Avastin, began in 1997. Source: Genentech Press Release

Phase III Results Show Avastin Plus Folfox4 Chemotherapy Significantly Extend Survival In Second-Line Metastatic Colorectal Cancer

Second Phase III Trial of Avastin Plus Chemotherapy to Show Improvement in Survival Over Chemotherapy Alone in Metastatic Colorectal Cancer South San Francisco, Calif. And Basel, Switzerland -- November 29, 2004 -- Genentech, Inc. (NYSE: DNA) and Roche (SWX Zurich) today announced that a randomized Phase III study of Avastin™ (bevacizumab) plus the FOLFOX4 chemotherapy regimen (oxaliplatin/5-FU/leucovorin), compared to FOLFOX4 alone, in second-line metastatic colorectal cancer patients achieved its primary endpoint of improving overall survival. Results from an interim analysis demonstrated that patients receiving Avastin plus FOLFOX4 had a 26 percent reduction in the risk of death, a hazard ratio of 0.74, compared to patients who received FOLFOX4 alone. Median survival for patients receiving Avastin plus FOLFOX4 was 12.5 months, compared to 10.7 months for those receiving FOLFOX4 alone, a 17 percent improvement. A preliminary assessment of the safety profile suggested that Avastin could be combined safely with FOLFOX4 and adverse events observed in this study were consistent with other clinical trials in which Avastin was combined with chemotherapy. The trial was sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health, and conducted by a network of researchers led by the Eastern Cooperative Oncology Group (ECOG). According to ECOG, preliminary study results will be presented during the ASCO Gastrointestinal Cancers Symposium, January 27-29, 2005 in Hollywood, Fla. "Avastin is the first and only targeted therapy to demonstrate improvements in survival in both first- and second-line metastatic colorectal cancer," said Hal Barron, M.D., Genentech senior vice president, development and chief medical officer." "This is the first Phase III study to evaluate Avastin in combination with an oxaliplatin-based chemotherapy regimen in patients with metastatic colorectal cancer. This study provides additional evidence that adding Avastin to chemotherapy results in a significant survival benefit for patients with either untreated or relapsed metastatic colorectal cancer. We plan to share these Phase III results with the FDA to discuss the filing of a supplemental Biologics License Application for this combination in this setting of metastatic colorectal cancer." This Phase III study was a randomized, controlled, multicenter trial that enrolled 829 patients with advanced colorectal cancer who had previously received a fluorouracil-based therapy and irinotecan, either alone or concurrently, for advanced disease or if their disease had relapsed within six months of concluding adjuvant treatment with these chemotherapy agents. The patients enrolled in this trial were randomized to receive treatment with the FOLFOX4 regimen with or without Avastin. Randomization to a third arm of the study evaluating single-agent Avastin was suspended in March 2003 on the recommendation of the Data Monitoring Committee overseeing the study when review of early results suggested that overall survival for patients in that group might be lower compared to that of patients treated on the other two arms. Results from this treatment arm have not yet been disclosed. A preliminary assessment of the safety profile suggested that Avastin could be combined safely with FOLFOX4 and treatment toxicities observed in this study were consistent with adverse events observed in other clinical trials in which Avastin was combined with chemotherapy. Adverse events included neuropathy attributed to FOLFOX4 and hypertension, managed with oral medications, and bleeding attributed to Avastin. About Avastin Avastin is a therapeutic antibody designed to inhibit Vascular Endothelial Growth Factor (VEGF), a protein that plays an important role in tumor angiogenesis and maintenance of existing tumor vessels. By inhibiting VEGF, Avastin is designed to interfere with the blood supply to a tumor, a process that is critical to a tumor's growth and metastasis. The FDA approved Avastin on February 26, 2004 as a first-line treatment for metastatic colorectal cancer in combination with intravenous 5-FU-based chemotherapy. Approval was based on data from two trials. The pivotal trial was a large, placebo-controlled, randomized study that demonstrated a prolongation in the median survival of patients treated with Avastin plus the IFL (5-FU/leucovorin/CPT-11) chemotherapy regimen by approximately five months, compared to patients treated with the IFL chemotherapy regimen alone (20.3 months versus 15.6 months). In addition, this study demonstrated an improvement in progression-free survival (PFS) of more than four months (10.6 months in the Avastin/IFL arm compared to 6.4 months in the IFL-alone arm). The survival and PFS results observed when Avastin is added to first-line chemotherapy are the longest ever reported in a randomized, Phase III study of patients with metastatic colorectal cancer. Based on data showing that VEGF may play a broad role in a range of cancers, Genentech is pursuing a late-stage clinical development program with Avastin evaluating its potential use in adjuvant and metastatic colorectal, renal cell (kidney), breast and non-small cell lung cancers. Avastin is also being evaluated in earlier stage trials as a potential therapy in prostate, ovarian, melanoma and several types of solid tumor cancers and hematologic malignancies. Additionally, Avastin is being studied in combination with Tarceva™ (erlotinib) in Phase II trials in both renal cell carcinoma and relapsed non-small cell lung cancer. Avastin Safety Profile In Genentech-sponsored studies in several tumor types, the most serious adverse events associated with Avastin use were gastrointestinal perforation, wound healing complications, hemorrhage, hypertensive crisis, nephrotic syndrome, congestive heart failure and arterial thromboembolic events including cerebrovascular accidents (stroke), myocardial infarctions, transient ischemic attacks, and angina. Other common adverse events were asthenia, pain, hypertension, diarrhea, leukopenia, and proteinuria. About VEGF and Tumor Angiogenesis The link between angiogenesis and cancer growth has been discussed by many researchers for decades. It wasn't until 1989 that a key growth factor influencing the process, VEGF, was discovered by Napoleone Ferrara, M.D., a staff scientist at Genentech. Dr. Ferrara and his team cloned VEGF, providing some of the first evidence that a specific angiogenic growth factor existed. This research was published in the journal Science in 1989. Dr. Ferrara then created a mouse antibody to this protein. In 1993, Dr. Ferrara and his team at Genentech, in a study published in Nature, demonstrated that the antibody directed against VEGF could suppress angiogenesis and tumor growth in preclinical models, providing compelling evidence that VEGF can play a critical role in tumor growth. Clinical studies with a humanized version of the antibody, Avastin, began in 1997. About Colorectal Cancer According to the American Cancer Society, more than 150 patients die every day from colorectal cancer in the United States. Colorectal cancer is the second leading cause of cancer death in the United States and the third most frequently diagnosed cancer. Approximately 147,000 new cases of colorectal cancer will be diagnosed in the United States in 2004. Source: Genentech Press Release

Preliminary Phase IIb Data Show Rituxan Improved Symptoms In Patients With Moderate-To-Severe Rheumatoid Arthritis

South San Francisco, Calif., Cabridge, Mass., San Diego, Calif. and Basel, Switzerland -- November 1, 2004 -- Genentech, Inc. (NYSE: DNA), Biogen Idec (Nasdaq: BIIB) and Roche (SWX Zurich) announced today that a Phase IIb clinical study of Rituxan® (Rituximab) met its primary endpoint of a greater proportion of Rituxan-treated patients achieving an American College of Rheumatology (ACR) 20 response at week 24, compared to placebo, in patients who were also treated with methotrexate (MTX). In this study, patients with moderate-to-severe rheumatoid arthritis (RA) who received two infusions of Rituxan over a two-week period in combination with a stable dose of MTX experienced improved symptoms compared to patients who received placebo and MTX. The benefit in the Rituxan-treated patients was present regardless of whether additional corticosteroids were administered. DANCER (Dose-Ranging Assessment International Clinical Evaluation of Rituximab in RA) is a Phase IIb study evaluating the efficacy and safety of varying doses of both Rituxan and corticosteroids in combination with a stable dose of MTX in patients who have failed one to five disease-modifying anti-rheumatic drugs (DMARDs) and are inadequately responding to MTX. Further analyses of the data are ongoing and will be submitted for presentation at an upcoming medical meeting. A preliminary analysis of the data did not reveal any unexpected safety signals. All regimens were generally well tolerated. Common side effects in the Rituxan arms included headache, nausea and upper respiratory infection. The reported rate of serious adverse events was not significantly different than seen in previous studies of Rituxan in RA. Rituxan is a therapeutic antibody that binds to the CD20 antigen on the surface of B cells (or B lymphocytes), which may play a key role in the inflammatory cascade of the disease. "These preliminary results are encouraging, as DANCER is the second randomized trial to demonstrate Rituxan's potential as a therapy for RA," said Hal Barron, M.D., Genentech's senior vice president, development and chief medical officer. "We are committed to understanding the pathophysiology of autoimmune diseases in order to provide patients and physicians with new therapies." "We look forward to presenting these data at an upcoming medical meeting and continuing our efforts to assess the potential for Rituxan as a treatment for this debilitating condition," said Burt Adelman, M.D., executive vice president, development, Biogen Idec. About the Study A total of 465 patients from the United States, Canada, Europe and Australia were randomized in this multi-center, randomized, double-blind, placebo-controlled study. Nine groups of patients received a stable dosage of MTX and a varying dose of Rituxan (placebo; 2 x 500 mg; 2 x 1000 mg) and corticosteroids (placebo; i.v. 200 mg; and i.v. 200 mg + p.o. 570 mg). ACR 20 indicates a 20 percent improvement in the number of swollen and tender joints, as well as a 20 percent improvement compared with baseline in three of five disease-activity measures: patient assessment, physician assessment, pain scale, Health Assessment Questionnaire and the value for one acute phase reactant (erythrocyte sedimentation rate or C-reactive protein). About RA RA is a debilitating autoimmune disease that affects more than two million Americans and hinders the daily activities of sufferers.1 RA occurs when the immune system inappropriately attacks joint tissue, causing chronic inflammation and irreversible destruction of cartilage, tendons and bones. Symptoms include inflammation of the joints, swelling, stiffness and pain. Additionally, since RA is a systemic disease, it can have effects in other tissues such as the lungs, eyes and bone marrow. About Rituxan Rituxan is a therapeutic antibody that selectively targets B cells. Rituxan received initial FDA approval in November 1997 for the treatment of relapsed or refractory low-grade or follicular, CD20 positive, B-cell non-Hodgkin's lymphoma (NHL). It also was approved in the European Union (EU) under the trade name MabThera® in June 1998. Genentech and Biogen Idec co-market Rituxan in the United States and Roche markets MabThera in the rest of the world, except Japan, where Rituxan is co-marketed with Zenyaku Kogyo Co. Ltd. Rituxan has been used to treat more than 380,000 patients worldwide. For a copy of the Rituxan full prescribing information, including Boxed Warning, please call 1-800-821-8590 or visit http://www.gene.com. Rituxan Safety Profile in NHL In NHL patients, the majority of patients experience infusion-related symptoms with their first Rituxan infusion. These symptoms include but are not limited to: flu-like fever, chills/rigors, nausea, urticaria, headache, bronchospasm, angioedema and hypotension. These symptoms vary in severity and generally are reversible with medical intervention. In rare instances, severe and fatal infusion-related reactions have occurred, nearly all of which have been associated with the first Rituxan infusion. These events appear as manifestations of an infusion-related complex and include hypoxia, pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, cardiogenic shock and tumor lysis syndrome. Patients who develop clinically significant infusion-related cardiopulmonary events should have their Rituxan infusion discontinued and receive medical treatment. In rare instances, severe mucocutaneous skin reactions have occurred that may be associated with Rituxan therapy. Many of these reactions have been described as paraneoplastic pemphigus and are known to be associated with various B-cell lymphomas, particularly NHL and chronic lymphocytic leukemia. Patients who develop a severe mucocutaneous skin reaction should have Rituxan discontinued and receive appropriate medical treatment, including a skin biopsy to guide therapy. Source: Genentech Press Release

Tarceva Plus Gemcitabine Improves Survival Compared To Gemcitabine Alone In First-Line Pancreatic Cancer Patients

Melville, N.Y.; South San Francisco, Calif.; And Basel, Switzerland -- September 20, 2004 -- OSI Pharmaceuticals, Inc., Genentech, Inc., and Roche announced that results from a randomized Phase III clinical study of the investigational drug Tarceva™ (erlotinib HCl), in combination with gemcitabine chemotherapy met its primary endpoint of improving survival. The international study demonstrated a statistically significant 23.5 percent improvement in overall survival for patients with locally advanced or metastatic pancreatic cancer when compared to patients receiving gemcitabine plus placebo. A hazard ratio of 0.81 and a p-value of 0.025 were observed (a hazard ratio of less than one indicates a reduction in the risk of death and a p-value of less than 0.05 indicates statistical significance). Median and one-year survival in the Tarceva™ plus gemcitabine arm were 6.4 months and 25.6 percent respectively compared to 5.9 months and 19.7 percent in the gemcitabine plus placebo arm. A statistically significant improvement in progression-free survival was also demonstrated, although no difference in tumor response was observed. A preliminary analysis of the safety data did not reveal any unexpected safety signal beyond that seen in prior use of Tarceva™ in both monotherapy and combination settings. As expected, rash and diarrhea were the principal Tarceva™ related side effects seen in the study. Tarceva™ is a small molecule oral therapy designed to inhibit the tyrosine kinase activity of the HER1/EGFR signaling pathway inside the cell, which may block tumor growth. This study, which was sponsored by OSI, was coordinated by the National Cancer Institute of Canada Clinical Trials Group at Queens University. Results from the study will be submitted for presentation at an appropriate peer-reviewed oncology meeting in the near future. "The results of this trial of Tarceva™ in combination with gemcitabine represent an important advancement in treating patients with pancreatic cancer," stated Malcolm Moore, M.D., Study Chair and Medical Oncologist at Princess Margaret Hospital and Chair of the Gastrointestinal Disease Site, NCIC Clinical Trials Group. "Pancreatic cancer is widely recognized as a difficult disease to treat and new therapeutic regimens are desperately needed. These results also demonstrate that the HER1/EGFR signaling pathway is an important target in pancreatic cancer, and offer hope that further progress can be made." "The positive outcome of this study is great news for pancreatic cancer patients and their families and adds to our growing understanding of the broad potential utility of Tarceva," said Colin Goddard, Ph.D., Chief Executive Officer of OSI Pharmaceuticals. "The results represent an important demonstration of Tarceva's activity beyond non-small cell lung cancer, and building on the results of our monotherapy studies in lung cancer, will support our ongoing efforts to further optimize the dosing and scheduling of Tarceva for the treatment of both pancreatic cancer and other cancers." "These data are important in that they open the door to a completely new approach in the treatment of pancreatic cancer, a disease in which currently only 20 percent of patients survive one year after diagnosis," said Hal Barron, M.D., Genentech's senior vice president, development and chief medical officer. "We will work closely with our collaborators to continue to understand these data, as well as determine additional clinical studies to optimize the potential use of Tarceva in this disease setting. The alliance will discuss these data with the FDA and other regulatory agencies to determine the next steps for Tarceva in pancreatic cancer." In July 2004, OSI completed the submission of a New Drug Application (NDA) with the FDA for Tarceva™, as a monotherapy for the treatment of patients with advanced non-small cell lung cancer (NSCLC) after failure of at least one standard chemotherapy regimen. About the Study This was a multi-center, randomized, double-blind, placebo-controlled Phase III study evaluating Tarceva™ at 100 mg/day or 150 mg/day in patients with locally advanced or metastatic pancreatic cancer. The study randomized patients to receive either gemcitabine plus concurrent Tarceva™ or gemcitabine plus placebo. A total of 569 patients were randomized in the study, 521 patients in the group who received 100 mg/day of Tarceva™ or placebo, and 48 patients in the group who received 150 mg/day of Tarceva™ or placebo. The study was an international study with sites in the United States, Asia, Canada, Europe, Australia and South America. About Pancreatic Cancer According to the World Health Organization more than 216,000 people worldwide are diagnosed each year with pancreatic cancer. The American Cancer Society predicts that in 2004 about 31,860 people in the United States will be found to have pancreatic cancer and about 31,270 will die of the disease. Most pancreatic tumors originate in the exocrine duct cells or in the cells that produce digestive enzymes (acinar cells). Called adenocarcinomas, these tumors account for nearly 95 percent of pancreatic cancers. About Tarceva™ Tarceva™ is designed to block tumor cell growth by inhibiting the tyrosine kinase activity of the HER1/EGFR receptor thereby blocking the HER1/EGFR signaling pathway inside the cell. Tarceva™ is currently being evaluated in an extensive clinical development program by a global alliance among OSI Pharmaceuticals, Genentech, and Roche. In April 2004, the alliance announced that Tarceva™ extended survival of patients receiving monotherapy Tarceva™ in a large randomized Phase III study in patients with advanced non-small cell lung cancer (NSCLC) after failure of at least one standard chemotherapy regimen. Tarceva™ is the first and only targeted therapy to demonstrate an improvement in survival for advanced NSCLC patients. Detailed results of the trial were presented in June at the 40th Annual American Society of Clinical Oncology (ASCO) meeting in New Orleans. The NDA was granted Pilot 1 Status under the FDA's Pilot 1 Program for Continuous Marketing Applications, a new program designed for investigational products that have been given Fast Track status such as Tarceva™, and that have demonstrated significant promise in clinical trials as a therapeutic advance over available therapy for a disease or condition. In addition, Roche recently submitted a marketing Authorization Application to the European health authorities for Tarceva™ for the monotherapy treatment of advanced NSCLC. About OSI Pharmaceuticals OSI Pharmaceuticals is a leading biotechnology company focused on the discovery, development, and commercialization of high-quality, next-generation oncology products that both extend life and improve the quality of life for cancer patients worldwide. OSI has a balanced pipeline of oncology drug candidates that includes both novel mechanism-based, gene-targeted therapies focused in the areas of signal transduction and apoptosis and a next-generation cytotoxic chemotherapy agent. OSI's most advanced drug candidate, Tarceva™, a small-molecule inhibitor of the HER1 gene, has successfully completed Phase III clinical trials for lung cancer and is the subject of an ongoing New Drug Application (NDA). OSI has a commercial presence in the U.S. oncology market where it exclusively markets Novantrone® (mitoxantrone concentrate for injection) for approved oncology indications and Gelclair® for the relief of pain associated with oral mucositis. OSI has also established Prosidion Limited, an independently operated diabetes and obesity subsidiary based in the United Kingdom. For additional information about the company, please visit http://www.osip.com. About Genentech BioOncology Genentech is committed to changing the way cancer is treated by establishing a broad oncology portfolio of innovative, targeted therapies with the goal of improving patients' lives. The company is the leading provider of anti-tumor therapeutics in the United States. Genentech is leading clinical development programs for Rituxan® (Rituximab), Herceptin® (Trastuzumab), and Avastin™ (bevacizumab) and markets all three products in the United States either alone (Avastin, which it recently launched in the United States, and Herceptin) or with Biogen Idec Inc. (Rituxan). Genentech has licensed Rituxan, Herceptin and Avastin to Roche for sale by the Roche Group outside of the United States. The company has a robust pipeline of potential oncology therapies with a focus on four key areas: angiogenesis, apoptosis (i.e. programmed cell death), the HER pathway and B-cell biology. Potential oncology therapies directed at the HER pathway include Tarceva™ (erlotinib HCl) and a therapeutic antibody currently in Phase II trials. Also in early development are a small molecule directed at the hedgehog pathway, a therapy targeting apoptosis and a humanized anti-CD20 antibody for hematology/oncology indications. 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, California and is traded on the New York Stock Exchange under the symbol DNA. For press releases and additional information about the company, please visit http://www.gene.com. Roche in Oncology Within the last five years the Roche Group including its partners Genentech in the US and Chugai in Japan has become the world's leading provider of anti-cancer treatments, supportive care products and diagnostics. Its oncology business includes an unprecedented four marketed products with survival benefit in different major tumour indications: Xeloda and Herceptin in advanced stage breast cancer, MabThera in non-Hodgkin's lymphoma, and Avastin in colorectal carcinoma. In the United States Herceptin, MabThera and Avastin are marketed either by Genentech alone or together with Biogen Idec Inc. Outside of the United States, Roche and its Japanese partner Chugai are responsible for the marketing of these drugs. The Roche oncology portfolio also includes NeoRecormon (anaemia in various cancer settings), Bondronat (prevention of skeletal events in breast cancer and bone metastases patients, hypercalcaemia of malignancy), Kytril (chemotherapy and radiotherapy-induced nausea and vomiting) and Roferon-A (hairy cell and chronic myeloid leukaemia, Kaposi's sarcoma, malignant melanoma, renal cell carcinoma). CERA is the most recent demonstration of the commitment to anaemia management. The Roche Group's cancer medicines generated sales of more than 3.3 billion Swiss francs in the first half of 2004. Roche is developing new tests, which will have a significant impact on disease management for cancer patients in the future. With a broad portfolio of tumour markers for prostate, colorectal, liver, ovarian, breast, stomach, pancreas and lung cancer, as well as a range of molecular oncology tests, we will continue to be the leaders in providing cancer focused treatments and diagnostics. Roche Oncology has four research sites (two in the US, Germany and Japan) and four Headquarter Development sites (two in the US, UK and Switzerland). Source: Genentech Press Release

Genentech And OSI Pharmaceuticals Initiate Phase IIIB Clinical Trial Of Tarceva In Advanced Non-Small Cell Lung Cancer

September 10, 2004 -- Genentech, Inc. (NYSE: DNA) and OSI Pharmaceuticals, Inc. (NASDAQ: OSIP) announced today the initiation of a Phase IIIB clinical study of the investigational therapy Tarceva™ (erlotinib HCl) in patients with second- and third-line non-small cell lung cancer (NSCLC) who have previously received chemotherapy. The clinical trial, called the ACT (Access to Care, Tarceva) trial, is a multi-center, open-label study of once-daily oral Tarceva, with endpoints of survival and response rate. The study will enroll a patient population consistent with the pivotal Tarceva trial, which is the basis for the New Drug Application (NDA) that was filed with the U.S. Food and Drug Administration (FDA) earlier this year. Patient enrollment for the trial has begun and will end when the FDA issues an approval decision regarding whether Tarceva is safe and effective as a monotherapy for the treatment of patients with advanced NSCLC after failure of at least one prior chemotherapy regimen. Patients interested in learning about the ACT trial can call 888-662-6728. About Tarceva Tarceva is an investigational product designed to block tumor cell growth by inhibiting the tyrosine kinase activity of the epidermal growth factor receptor (HER1/EGFR), thereby blocking the HER1/EGFR signaling pathway inside the cell. Tarceva is currently being evaluated in an extensive clinical development program by a global alliance of Genentech, OSI Pharmaceuticals and Roche. In July 2004, OSI filed an NDA for Tarceva with the FDA as a monotherapy for patients with advanced NSCLC after failure of at least one standard chemotherapy regimen. The FDA designated Tarceva Pilot 1 status under its Pilot 1 Program for Continuous Marketing Applications, a new program designed for investigational products that have been granted Fast Track status such as Tarceva, and that have demonstrated significant promise in clinical trials as a therapeutic advance over available therapy for a disease or condition. Tarceva is the first and only targeted therapy to demonstrate an improvement in survival for advanced NSCLC patients. The NDA filing is based on a pivotal Phase III double-blind, placebo-controlled trial, which included 731 patients and that compared Tarceva to placebo in the treatment of patients with advanced NSCLC after failure of at least one prior chemotherapy regimen. Detailed results of the trial were presented in June at the 40th Annual American Society of Clinical Oncology (ASCO) meeting in New Orleans. Safety In line with previous clinical studies, adverse events that occurred more often with patients treated with Tarceva in the pivotal trial included rash and diarrhea, which were generally mild to moderate in severity. Seventy-five percent of patients receiving Tarceva exhibited rash (versus 17 percent in the placebo group) and 54 percent of patients receiving Tarceva experienced diarrhea (versus 18 percent for placebo). Dose reductions occurred for rash and diarrhea only in the Tarceva arm, 10 percent and four percent respectively. In the pivotal study, severe pulmonary events, including potential cases of interstitial lung events, were infrequent and were equally distributed between treatment arms. About Non-Small Cell Lung Cancer According to the World Health Organization, there are more than 1.2 million cases worldwide of lung and bronchial cancer each year, causing approximately 1.1 million deaths annually. According to the National Cancer Institute, lung cancer is the single largest cause of cancer deaths in the United States and is responsible for nearly 30 percent of cancer deaths in the country. NSCLC is the most common form of lung cancer and accounts for almost 80 percent of cases. Source: Genentech Press Release, Investor Relations

Decoy Protein Shows Promise As Potential Cancer Therapy July 19, 2004. Two recent research studies published in the July issue of Cancer Cell demonstrate that targeting a portion of a protein associated with many human cancers, including breast, lung, liver, kidney, and colorectal cancers, may have significant potential therapeutic applications with less toxicity than more general inhibitors of the same signaling pathway. Fundamental processes like cell proliferation, migration, differentiation, and survival are regulated in part by hepatocyte growth factor (HGF). HGF controls and coordinates many events that are critical for embryonic development and for adult wound healing and tissue regeneration. However, in addition to playing a necessary role in these essential normal processes, HGF signaling through its receptor Met is usurped by many tumors to promote growth, survival, and metastases. Dr. Paolo Michieli and colleagues from the University of Torino Medical School in Italy examined whether targeted inhibition of HGF/Met signaling may be an effective anticancer therapeutic. The researchers engineered a truncated version of the Met receptor that consisted only of the receptor's extracellular domain. This version of Met, called decoy Met, was soluble and could be systemically introduced into mice. Decoy Met inhibited the growth and survival of a variety of human tumor cells that were grafted into mice, interfered with the ability of the tumors to establish a blood supply, and prevented the tumor cells from spreading. Importantly, decoy Met did not interfere with normal physiological functions in adult mice. The authors suggest that the extracellular portion of the receptor present in decoy Met successfully competes for HGF binding and may be a promising therapeutic agent. A second study by Dr. Dineli Wickramasinghe and colleagues from the Department of Molecular Oncology at Genentech in San Francisco examined a very specific part of the extracellular domain of the Met receptor, called the Sema domain. The Met Sema domain was required for HGF-stimulated Met activation in tumor cells. In addition, the Met receptor dimerization, a process that is necessary for full activation of Met and therefore activation of signaling molecules downstream of Met, only occurred when the Sema domain was intact. This is significant because hyperactivation of the Met receptor, even in the absence of HGF, is common in many types of cancer. When the Sema domain by itself was introduced into Met-overexpressing tumor cells, it blocked receptor activation and downstream signals that stimulate cell motility and migration. According to Dr. Wickramasinghe, "These observations point to the exciting prospect of treating Met-overexpressing tumors not only by targeting the Sema domain of Met but also by utilizing the Sema domain itself as a biotherapeutic." Source: Cell Press