Merck’s  Strategic Plan, Pipeline in Progress and Implementation of a New Model     -Merck's Pipeline Continues to Progress with Seven Products in Phase III Development-   -Company Expects to File Applications for Expanded Indications on GARDASIL and ISENTRESS in 2008-   -Merck Intends to Initiate a Sequenced Phase III Program for Anacetrapib in 2008-   -Successful Early Launches of GARDASIL, JANUVIA, JANUMET and ISENTRESS-   -Reflect Better Alignment of Product Development and Commercialization Efforts; Replicable Model to Reduce Time to Market of New Medicines and Vaccines-   -Company Remains on Track to Deliver Long-Term, Double-Digit Compound Annual EPS Growth from 2005 to 2010, Excluding Certain Items-    Dec. 11, 2007 - Merck & Co., Inc. hosted its Annual Business Briefing and reviewed the progress the Company has achieved under a strategic plan designed to re-engineer the way Merck develops and distributes medicines and vaccines worldwide.  Since 2005, Merck's senior management team has been developing and implementing a new operating model under which customer focus drives drug discovery, development and marketing at the Company, Merck Chairman, President and Chief Executive Officer Richard T. Clark told investors and analysts today at the Merck Annual Business Briefing.   "We are realizing the benefits of the successful execution of our strategy.  We have created a model for success that encompasses every aspect of our business, including R&D, manufacturing and commercialization," Mr. Clark said.  "As a result, Merck has a sustainable business model that will allow us to realize the goals we set for 2010 and to position the Company for future success."   During his presentation, Mr. Clark highlighted some of the goals the Company has met or expects to meet by 2010, including:   * Launched seven new drugs and vaccines in the past two years, many of them first- or best-in-class * Compound annual revenue growth of 4 percent to 6 percent from 2005 to 2010, including 50 percent of all joint-venture revenue * Double-digit compound annual earnings per share (EPS) growth from 2005 to 2010, excluding certain items * Plan to return product gross margin to pre-ZOCOR levels in 2008 * Reduced clinical development cycle times relative to the pharmaceutical sector   "The changes we have made and are continuing to make at Merck are designed to be sustained over the long term.  They represent a true model for success," Mr. Clark said.  "We have not focused only on short-term successes, but we are making the necessary investments to ensure the success of this Company beyond the year 2010."   Merck's Late-Stage Pipeline Continues to Grow Building on the seven U.S. Food and Drug Administration (FDA) approvals Merck has received in the past two years, the Company anticipates regulatory action will be taken in 2008 on two New Drug Applications (NDA) for EMEND for Injection and CORDAPTIVE, the proposed brand name for MK-0524A.  Also in 2008, the Company anticipates making two additional NDA filings with the FDA for MK-0524B, simvastatin combined with laropiprant and extended-release niacin, and MK-0364, taranabant, an investigational medication for the treatment of obesity, said Peter S. Kim, Ph.D., president of Merck Research Laboratories.   Additionally, Dr. Kim said, the Company anticipates making two supplemental filings with the FDA in 2008: one for GARDASIL, Merck's vaccine for the prevention of cervical cancer, for an expanded indication for adult women through age 45, and one for ISENTRESS, a first-in-class integrase inhibitor for the treatment of HIV-1 infection, for an expanded indication for use in treatment-naïve patients.   During his presentation, Dr. Kim also detailed the following seven drug candidates currently in Phase III development:   -MK-0524B is a drug candidate that combines the novel approach to raising HDL-cholesterol (HDL-C) and lowering triglycerides from extended-release niacin combined with laropiprant with the proven benefits of simvastatin in one combination product. The candidate already is in Phase III development, and Merck continues to anticipate filing an NDA for MK-0524B in 2008.   -MK-0364, taranabant, is a highly selective cannabinoid-1 receptor inverse agonist that in early clinical studies has demonstrated weight loss versus placebo. The Company previously announced the initiation of a targeted Phase III program in 2006. Merck anticipates filing an NDA in 2008.   -MK-0974, an investigational oral calcitonin gene-related peptide receptor antagonist, utilizes a new mechanism for the treatment of migraines that has demonstrated efficacy at least comparable to triptans in early clinical studies. The drug candidate entered Phase III development during 2007. The Company anticipates filing an NDA in 2009.   -MK-7418, rolofylline, is a Phase III investigational drug being evaluated for the treatment of acute heart failure. Merck acquired the drug candidate as part of the 2007 acquisition of NovaCardia, Inc. and anticipates filing an NDA with the FDA in 2009. -MK-8669, deforolimus, is a novel mTOR (mammalian target of rapamycin) inhibitor being evaluated for the treatment of cancer. The drug candidate is being jointly developed and commercialized with ARIAD Pharmaceuticals, Inc. under an agreement reached in mid-2007. The Company anticipates filing an NDA in 2010.   -HEPLISAV, a novel investigational hepatitis B vaccine, currently is being evaluated in a Phase III clinical trial in adults and in patients undergoing dialysis treatment. Merck is jointly developing HEPLISAV with Dynavax Technologies Corporation under an agreement reached in late 2007. Merck anticipates filing an NDA in 2010 for adults.   -MK-0822, odanacatib, is a highly selective inhibitor of cathepsin K enzyme, which is being evaluated for the treatment of osteoporosis. The Phase III program began in mid-2007. Merck anticipates filing an NDA with the FDA in 2012.   Dr. Kim also provided an update on the development of MK-0859, anacetrapib, an inhibitor of the cholesterol ester transfer protein (CETP) that in early clinical trials has shown promise in lipid management by raising HDL-C and reducing LDL-cholesterol (LDL-C) without raising blood pressure.   "In clinical studies, inhibition of CETP raises plasma HDL-C levels and decreases LDL-C levels, which represents a potential therapeutic intervention to reduce the risk of coronary artery disease," Dr. Kim said.  "The safety and tolerability profile of anacetrapib was comparable to placebo in clinical studies conducted to date.  In 2008, we plan to initiate a sequenced Phase III program to obtain additional clinical experience in patients before initiating an outcomes study."   As of Dec. 11, 2007, Merck's updated pipeline chart includes 25 distinct candidates in Phase I and 15 in Phase II.  In addition, there are seven candidates currently in Phase III, one submission currently under FDA review, and another that has received an approvable letter and is awaiting further regulatory action.  In its pipeline review, Merck does not include backup candidates; additional indications for candidates in the same therapeutic area; or additional claims, line extensions or formulations for existing products.   New Commercial Model More Effective and Efficient Kenneth C. Frazier, executive vice president and president, Global Human Health, provided an update on the early successes of Merck's ongoing endeavor to align the Company's product research, development and marketing efforts.   In his presentation, Mr. Frazier said that the successful launches and strong global uptake of GARDASIL, JANUVIA and JANUMET are the result of a replicable model that continues to evolve.  He said that the Merck model is not only proving more cost efficient but is allowing Merck to reduce the time it takes to get new medicines and vaccines into markets around the world.   As part of this effort, Merck Global Human Health, aligned with Merck Research Laboratories and Merck Manufacturing, is utilizing the latest technologies and broadening its engagement with customers, physicians and scientific leaders to get needed medicines and vaccines through the development pipeline and to patients sooner, Mr. Frazier said.   The strong sales of Merck's new products, coupled with continued strong growth from in-line products, especially SINGULAIR, should allow Merck to offset the impact of the loss of U.S. marketing exclusivity for FOSAMAX and other products, Mr. Frazier said.  He also said that the Company has achieved a nearly fourfold increase in global vaccine sales since 2005 and remains on track to double sales in emerging markets to $2 billion by 2010.   Merck Reaffirms 2007 and 2008 Financial Guidance During his presentation, Executive Vice President and Chief Financial Officer Peter N. Kellogg reaffirmed Merck's previously disclosed financial outlook for 2007 and 2008.   "With our 2007 and 2008 guidance, it is clear that our products are driving a healthy top line despite lapping the ZOCOR expiry and the upcoming FOSAMAX exposure," Mr. Kellogg said.  "We are very pleased with our results in 2007, and we anticipate continued strong financial performance from our key franchises in 2008.   "As I previously noted on Dec. 4, our financial guidance in 2008 represents the next step in our journey to reach our stated 2010 top- and bottom-line goals.  Despite the loss of marketing exclusivity for FOSAMAX in the United States in February 2008, the Company anticipates solid earnings growth in 2008," Mr. Kellogg added.   He continued, "As we disclosed in 2005, Merck's new and in-line pharmaceutical products and vaccines are expected to drive revenue at a compound annual growth rate of 4 percent to 6 percent from 2005 through 2010, including 50 percent of the revenues from the joint ventures from which Merck derives equity income.  We also expect that we can fully support our expanding pipeline with mid-single-digit compound annual growth in research funding over the same period.  The productivity generated by our ongoing cost management initiatives allows Merck to fully capitalize on the promise of our expanding product portfolio while maintaining marketing and administrative expense at 2006 levels."   About Merck Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first.  Established in 1891, Merck discovers, develops, manufactures and markets vaccines and medicines to address unmet medical needs.  The Company devotes extensive efforts to increase access to medicines through far-reaching programs that not only donate Merck medicines but help deliver them to the people who need them.  Merck also publishes unbiased health information as a not-for-profit service.  For more information, visit www.merck.com.   Forward-Looking Statement This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995.  These statements are based on management's current expectations and involve risks and uncertainties, which may cause results to differ materially from those set forth in the statements.  The forward-looking statements may include statements regarding product development, product potential or financial performance.  No forward-looking statement can be guaranteed, and actual results may differ materially from those projected.  Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.  Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Merck's business, particularly those mentioned in the risk factors and cautionary statements set forth in Item 1A of Merck's Form 10-K for the year ended Dec. 31, 2006, and in its periodic reports on Form 10-Q and Form 8-K, which the Company incorporates by reference.     Source: Merck Inc.

FDA's New Generic Drug Program-GIVE Q&A with Gary J. Buehler, RPh.,  Director of FDA’s Office of Generic Drugs (OGD)   Credit: FDA Consumer Health Information e-published on MedicineandBiotech.com December 1st, 2007        VIEW VIDEO   Gary J. Buehler, RPh., is Director of the Office of Generic Drugs (OGD) in FDA's Center for Drug Evaluation and Research (CDER). A graduate of Temple University's School of Pharmacy, Mr. Buehler joined FDA in 1986.   Q: What are generic drugs? A: A generic drug is identical to a brand-name drug in dosage form, safety, strength, route of administration, quality, performance, and intended use. Although the active ingredient is chemically the same as the branded counterpart, a generic drug is typically sold at a substantial discount from the branded product price.     Q: If they are the same, why do generic drugs cost less than their brand-name counterparts? A: Creating a drug and conducting clinical trials is expensive. Generic drug makers don't develop a drug from scratch or have to conduct studies to prove safety and effectiveness. As the result, their expenses for bringing generic drugs to market are less. But generic drug makers must show that their product performs in the same way as the brand-name drug.     Q: What is FDA's role regarding generic drugs? A: CDER ensures that both brand-name and generic drugs are safe and effective, and that their health benefits outweigh their known risks. And, just as it does with brand-name drugs, the agency closely inspects generic makers' production sites and assures products approved are manufactured according to regulations regarding good manufacturing practices.   Health professionals and consumers can be assured that FDA-approved generic drugs have met the same rigid manufacturing standards as the brand-name drug.     Q: What is the Generic Initiative for Value and Efficiency (GIVE) program? A: GIVE is an initiative aimed at optimizing OGD's generic drug review process to increase efficiency. The goals of GIVE are to approve higher numbers of applications for generic products and expedite review of applications for which there are few generics available.     Q: What will the benefits of this program be for the average consumer? A: Consumers will have timely access to safer, higher-quality generic drugs. A more efficient regulatory and approval process will maintain FDA's high standards for generic drug products for the public, while increasing the number of available products.     Q: Why is the GIVE program necessary? A: Over the last three to four years, the number of abbreviated new drug applications submitted to our office has increased. This has led to a growing list of pending applications. We've made a number of successful process improvements during this time. In fact, the office approved a record number of applications during the past two years. We approved 510 products in 2006, and approved more than 650 in the fiscal year that just ended.   But the advancement of medical science and the related increasing cost of health care and disease prevention have caused the role of OGD and its review staff to grow. The number of firms producing generic products and the number of products each firm proposes are growing at an unforeseen pace. The improvements we have made serve to unify and enhance the review process to address the growing workload, and to increase the efficiency of our office's review efforts.     Q: How will the goals of GIVE be accomplished? A: GIVE will work by combining our office's various efforts into one harmonized activity to implement process improvements throughout the entire program. The initiative is a review-oriented program that is focused on three main areas:   * Mobilizing staff efforts to increase review productivity. * Optimizing the capacity and capability of all assets within OGD, and leveraging wherever possible resources from other FDA components. * Using every avenue possible to recruit, hire and train reviewers for our critical-need areas.     FOR MORE INFORMATION VISIT Generic Initiative for Value and Efficiency (GIVE) at http://www.fda.gov/oc/initiatives/advance/generics.html

GlaxoSmithKline and Tolerx form Worldwide Collaboration for Development and Commercialization of Novel Medication

---Collaboration focuses on type 1 diabetes and other autoimmune indications---   October 2007. GlaxoSmithKline and Tolerx, Inc. today announced the execution of a worldwide alliance to develop and commercialize otelixizumab (TRX4), a novel humanized anti-CD3 monoclonal antibody that has potential across a broad range of autoimmune and immune-mediated inflammatory diseases, including type 1 diabetes. Otelixizumab has been evaluated in type 1 diabetes in two Phase II studies and in psoriasis in two Phase I studies. In clinical trials, otelixizumab has been shown to preserve the function of insulin-producing beta cells in the pancreas in patients with type 1 diabetes, reducing the amount of administered insulin needed to control blood glucose levels.   Under the terms of the agreement, Tolerx will have responsibility for the Phase III clinical programme for type 1 diabetes in the US up to and including regulatory submission of the biologics license application (BLA). Tolerx has the option to co-promote otelixizumab in type 1 diabetes in the US with GSK, while GSK will have exclusive rights to develop and commercialise otelixizumab in all other indications in the rest of the world. GSK also has the exclusive right to develop the paediatric indication for type 1 diabetes in the US.    As part of the collaboration, Tolerx will receive an upfront payment, equity and advance R&D funding totaling $70 million. In addition, Tolerx may receive up to $155 million in future development costs of otelixizumab in type 1 diabetes. Tolerx may earn up to $350 million in milestone payments, assuming successful development and approvals of otelixizumab for type 1 diabetes and multiple additional indications. Tolerx may also receive up to $175 million in sales milestone payments based on tiered net sales thresholds of otelixizumab. Tolerx will be entitled to receive tiered, double-digit royalty payments on worldwide sales of otelixizumab in all indications. At the time of an initial public offering of Tolerx’s common stock and at the request of Tolerx and certain other conditions, GSKwill invest up to an additional $10 million in Tolerx’s common stock.    Dr. Moncef Slaoui, Chairman of Research and Development at GSK, commented, “Otelixizumab is another welcome addition to GSK’s rapidly expanding biopharmaceuticals pipeline. This is a key area of future growth and investment for GSK and, as a novel treatment for many T cell-mediated diseases, the potential of otelixizumab is significant. Together with Tolerx, who are pioneers in this area of science, we hope to realise the potential of this compound and bring a valuable new treatment option to patients suffering from type 1 diabetes and other autoimmune disorders.”   "GSK brings a wealth of experience, expertise, and global resources to this collaboration. The agreement with GSK enables us to operationally leverage Tolerx’s expertise in therapeutic immune regulation, expand the development of otelixizumab in type 1 diabetes and other indications, and capitalize on GSK’s considerable worldwide development, regulatory, and commercialisation infrastructure and experience,” said Dr. Douglas J. Ringler, President and Chief Executive Officer of Tolerx. “Moreover, it provides the infrastructural support required to advance our goal of being first-to-market with otelixizumab in type 1 diabetes. We anticipate the collaboration will allow the potential of this novel therapy to be fully explored globally, not only for the treatment of patients with type 1 diabetes but also for those with autoimmune disorders for which the current standard of care is inadequate.”   About type 1 diabetes Diabetes (medically known as diabetes mellitus) is the name given to disorders in which the body has difficulty regulating its blood glucose, or blood sugar levels. There are two major types of diabetes: type 1 and type 2. Type 1, also called juvenile diabetes or insulin-dependent diabetes, is a disorder of the body's immune system. In type 1 diabetes, the pancreas produces little or no insulin as a result of the immune system attacking and destroying the insulin-producing beta cells in the pancreas. Therefore, type 1 diabetes patients require frequent administration of insulin therapy each day to control their blood sugar levels.   About otelixizumab Otelixizumab is a monoclonal antibody that binds to a receptor component found on all T cells known as CD3, which is involved in normal T cell signaling. Otelixizumab is designed to block the function of autoreactive T-effector cells that attack the body’s tissues and cause autoimmune disease while inducing a subset of T cells called T-regulatory cells that are thought to protect against T-effector cell damage well after the drug has been eliminated from the body. In a Phase II clinical study of subjects with new-onset type 1 diabetes, otelixizumab demonstrated the potential to preserve the function of insulin-producing beta cells in the pancreas and reduce the amount of administered insulin needed to control blood glucose levels for up to 18 months after only a single six day course of therapy. In the study, residual betacell function was assessed by measuring glucose clamp-induced C-peptide release before and after the administration of glucagon. Otelixizumab administration was associated with transient symptoms of flu-like syndrome and transient Epstein-Barr Virus (EBV) reactivation. Tolerx has completed dose optimisation studies in subjects with type 1 diabetes and psoriasis and has identified a dosing regimen that thus far has significantly reduced or eliminated these side effects while maintaining important biological activity.   About GlaxoSmithKline GlaxoSmithKline is one of the world's leading research-based pharmaceutical and healthcare companies and is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For more information, visit GlaxoSmithKline at www.gsk.com.   About Tolerx Tolerx is a biopharmaceutical company engaged in the discovery and development of novel therapies to treat patients with immune-mediated diseases. Tolerx currently has two antibodies in clinical development: otelixizumab in type 1 diabetes and psoriasis, and TRX1 in cutaneous lupus erythematosus (CLE). TRX1 is a humanised anti-CD4 antibody that is being developed in collaboration with Genentech, Inc. Tolerx is also engaged in preclinical development of new product candidates that induce immunological tolerance for the treatment of autoimmune diseases and circumvent tolerance for the treatment of cancer or chronic viral diseases. For more information, please visit www.tolerx.com.   GlaxoSmithKline forward-looking statements Under the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995, GSKcautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Factors that may affect GSK's operations are described under 'Risk Factors' in the Operating and Financial Review and Prospects in the company's Annual Report on Form 20-F for 2006.     Source: GSK Press Release Share your Favorite articles on the following Social Networks: Share on Facebook

Rasilez® Receives EU Approval, the First Major Innovation in High Blood Pressure Treatment for More than a Decade

• A direct renin inhibitor, Rasilez is the first medicine to directly target the source of high blood pressure • Alone or in combination with other medicines, Rasilez provides significant blood pressure lowering for 24 hours and beyond • Nearly half of adults in Europe’s largest countries suffer from high blood pressure, which can cause heart attack, stroke and death • Strong need for new therapies since nearly 70% of high blood pressure patients still not achieving treatment goals     Basel, August 27, 2007 – Rasilez® (aliskiren), the first new type of high blood pressure medicine in more than a decade, has been approved for use in the European Union. Nearly half of all adults in Europe’s largest countries, such as Germany, Italy and the UK, suffer from this potentially life-threatening condition5.   The European Commission approved Rasilez for the treatment of high blood pressure alone or in combination with other high blood pressure medicines, based on data from more than 7,800 patients in 44 clinical trials. The approval applies to all 27 EU member states plus Iceland and Norway.   “Rasilez is the first medicine to directly target high blood pressure at its source, the enzyme renin,” said Dr. Roland Schmieder, Professor of Medicine at the University of Erlangen-Nuremberg, Germany. “As doctors, our biggest challenge is getting blood pressure under control in the first place and then keeping it there. Because Rasilez works well alone or with other medicines, it shows good promise in helping patients, even those who haven’t yet achieved control with other medicines.”   Experts estimate that nearly one billion people globally have high blood pressure and that nearly 70% of these people do not reach healthy blood pressure levels 6,7. As a result, they live at risk of complications like heart attack, stroke, kidney failure, blindness and death, creating a strong need for new high blood pressure therapies6.   Rasilez is the first in a new class of medicines called direct renin inhibitors. It acts by directly inhibiting renin, an enzyme that triggers a process that can lead to high blood pressure. This new medication received its first approval in March 2007 from the US Food and Drug Administration under the brand name Tekturna®, and has also been approved in Switzerland.   When used alone, Rasilez demonstrates greater blood pressure lowering than other commonly-used blood pressure medicines like angiotensin converting enzyme (ACE) inhibitors8 and the diuretic hydrochlorothiazide (HCT)9.   For patients already taking other medicines, but not at their blood pressure goal, Rasilez provides additional blood pressure lowering when added to existing therapy. This additional benefit is seen when Rasilez is added to ACE inhibitors10, angiotensin II receptor blockers (ARBs)3, calcium channel blockers (CCBs)11 or HCT12, while offering a placebo like tolerability profile3.   Rasilez consistently lowers blood pressure for 24 hours and beyond 1,2. This is an important treatment consideration, because many high blood pressure medicines fail to work around the clock, especially during the early morning hours when blood pressure often surges.   “Direct renin inhibition is the only major innovation in treating high blood pressure for more than a decade,” said James Shannon, MD, Global Head of Development at Novartis Pharma AG.   “Rasilez is the first approved medicine that helps patients reach their blood pressure  goal by controlling the renin system. Novartis is proud to bring this important new medicine to the fight against this damaging and rapidly increasing disease.”   The long-term potential of Rasilez and direct renin inhibition is being studied in a clinical program known as ASPIRE HIGHER, focusing on the benefits of using Rasilez in high blood pressure patients with heart failure or kidney failure. Data from the program are expected to be released later this year.   High blood pressure – and its consequences – is the world’s No. 1 cause of death. This condition, also called hypertension, occurs when the blood in the body moves through the blood vessels at a higher pressure than normal and causes damage to the arteries, kidneys, brain and other vital organs that can ultimately lead to heart failure.   Rasilez was developed in collaboration with Speedel.   Disclaimer The foregoing release contains forward-looking statements which can be identified by the use of terminology such as “can”, “potentially”, “promise”, “estimate”, “potential”, “expected”, or similar expressions, or by express or implied discussions regarding potential future revenue from Rasilez. Such forward-looking statements reflect the current views of the Company regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that Rasilez will reach any particular sales levels. In particular, management’s expectations regarding Rasilez could be affected by, among other things unexpected clinical trial results, including additional analysis of clinical data, or unexpected new clinical data; unexpected regulatory actions or delays or government regulation generally; competition in general; increased government, industry, and general public pricing pressures; our ability to obtain or maintain patent or other proprietary intellectual property protection; and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.   For more information, please visit http://www.novartis.com   References 1. Oh BH, Mitchell J, Herron JR, et al. Aliskiren, an oral renin inhibitor, provides dose-dependent efficacy and sustained 24-hour blood pressure control in patients with hypertension. J Am Coll Cardiol 2007;49:1157–1163. 2. Sica D, Gradman AH, Lederballe O, et al. Aliskiren, a novel renin inhibitor, is well tolerated and has sustained BP-lowering effects alone or in combination with HCTZ during long-term (52 weeks) treatment of hypertension. Eur Heart J 2006;27(Suppl):121 P-797. 3. Oparil S, Yarows SA, Patel S, et al. Antihypertensive efficacy and safety of dual renin system intervention with aliskiren, an oral direct renin inhibitor, and valsartan: a randomized, double-blind comparison versus monotherapy. Lancet 2007;370:221–229. 4. Keefe DL, Andersen K, Weinberger MH, et al. Blood pressure lowering effects persist following the last dose of long-term therapy with aliskiren, an oral direct renin inhibitor. J Am Coll Cardiol 2007;49(9 Suppl A):372A P-1014-204. 5. Kearney PM, Whelton M, Reynolds K, et al. Global burden of hypertension: analysis of worldwide data. Lancet 2005;365:217–223. 6. Chobanian AV, Bakris GL, Black HR, et al. and the National High Blood Pressure Education Program Coordinating Committee. The seventh report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Hypertension 2003; 42:1206–1252. 7. Ong KL, Cheung BMY, Man YB, et al. Prevalence, awareness, treatment, and control of hypertension among United States adults 1999–2004. Hypertension 2007;49:69–75. 8. Andersen K, Weinberger MH, Egan B, et al. Aliskiren-based therapy lowers blood pressure more effectively than ramipril-based therapy in patients with hypertension: a 6-month, randomized, double blind trial. J Am Coll Cardiol 2007;49(9 Suppl A):371A P-1014-173. 9. Schmieder RE, Philipp T, Guerediaga J, et al. Aliskiren-based therapy lowers blood pressure more effectively than hydrochlorothiazide-based therapy in patients with hypertension. Journal of Clinical Hypertension 2007;9 Suppl A(5):A182 P-436. 10. Uresin Y, Taylor A, Kilo C, et al. Aliskiren, a novel renin inhibitor, has greater BP lowering than ramipril and additional BP lowering when combined with ramipril in patients with diabetes and hypertension. J Hypertens 2006;24:S82 P-269. 11. Munger MA, Drummond W, Essop ER, et al. Aliskiren as add-on to amlodipine provides significant additional blood pressure lowering without increased oedema associated with doubling the amlodipine dose. Eur Heart J 2006;27(Suppl):117 P-784. 12. Villamil A, Chrysant SG, Calhoun D, et al. Renin inhibition with aliskiren provides additive antihypertensive efficacy when used in combination with hydrochlorothiazide. J Hypertens 2007;25:217–226. # # #   Share your Favorite articles on the following Social Networks: Share on Facebook

Bayer HealthCare and Regeneron Initiate Phase 3 Global Development Program for VEGF Trap-Eye in Wet Age-related Macular Degeneration (AMD)

---Study will compare the VEGF Trap-Eye to Genentech’s  ranibizumab (Lucentis®)---   Leverkusen, Germany, and Tarrytown, NY (August 03, 2007) – Bayer HealthCare AG and Regeneron Pharmaceuticals, Inc. announced today that the companies have initiated a Phase 3 study of the VEGF Trap-Eye in the neovascular form of age-related macular degeneration (wet AMD). The study will be a non-inferiority comparison of the VEGF Trap-Eye and ranibizumab (Lucentis®, a registered trademark of Genentech, Inc.), an anti-angiogenic agent approved for use in wet AMD. The study will be conducted pursuant to a Special Protocol Assessment from the U.S. Food and Drug Administration (FDA). This trial, known as VIEW 1 (VEGF Trap: Investigation of Efficacy and safety in Wet age-related macular degeneration), is the first study in the companies’ Phase 3 global development program in wet AMD which is planned to be carried out in the U.S., Europe and other parts of the world.   “Age-related macular degeneration continues to be one of the leading causes of blindness in adults, and new therapies are essential to providing optimal patient care,” stated Jeffrey Heier, M.D., a clinical ophthalmologist at Ophthalmic Consultants of Boston and chair of the steering committee for the trial. “The results of early phase studies of VEGF Trap-Eye suggest it has the potential to be a highly efficacious treatment with less frequent administration. If these results are confirmed in Phase 3 trials, it would be important for both patients and physicians and would be a significant advance in the treatment of these patients.”   “We will continue in our effort to improve the lives of patients suffering from wet AMD and the initiation of the first Phase 3 study is an important step forward in the development of this investigational therapy”, said Kemal Malik, M.D., Member of the Bayer HealthCare Executive Committee, responsible for Global Development. “Our program is designed to investigate VEGF Trap-Eye’s potential to improve vision in patients with wet AMD with less frequent dosing than every four weeks.“   The randomized, double-masked Phase 3 study, is expected to enroll approximately 1,200 patients in more than 200 centers throughout the United States and Canada. The study will evaluate the safety and efficacy of the VEGF Trap-Eye at doses of 0.5 milligrams (mg) and 2.0 mg administered at four-week dosing intervals and 2.0 mg at an eight-week dosing interval, compared to 0.5 mg of ranibizumab administered every four weeks, consistent with its labeled dosing schedule.   The primary endpoint of the study is the proportion of patients treated with the VEGF Trap-Eye who maintain or improve vision at the end of one year, compared to ranibizumab patients. Visual acuity is defined as the total number of letters read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Maintenance of vision is defined as losing fewer than 3 lines (equivalent to 15 letters) on the ETDRS chart. After the first year of treatment, patients will continue to be treated and followed for another year.   In an analysis of interim data from the ongoing Phase 2 trial in wet AMD, where patients were treated with the VEGF Trap-Eye either monthly or quarterly, combined data for all patients demonstrated a statistically significant reduction in retinal thickness and improvement in visual acuity after 12 weeks, compared to baseline. There were no drug-related serious adverse events, and treatment with the VEGF Trap-Eye was generally well-tolerated. The most common adverse events were those typically associated with intravitreal injections. The interim results of this Phase 2 trial were presented at the annual meeting of the Association for Research in Vision and Ophthalmology (ARVO) this past May. The Companies expect to report final primary endpoint results of the trial at a scientific meeting later this quarter.   Bayer HealthCare and Regeneron are collaborating on the global development of the VEGF Trap-Eye for the treatment of wet AMD, diabetic eye diseases, and other eye diseases and disorders. Bayer HealthCare will market the VEGF Trap-Eye outside the United States, where the parties will share equally in profits from any future sales of the VEGF Trap-Eye. Regeneron maintains exclusive rights to the VEGF Trap-Eye in the United States.   About the VEGF Trap-Eye Vascular endothelial growth factor (VEGF) is a naturally occurring protein in the body whose normal role is to trigger formation of new blood vessels (angiogenesis) to support the growth of the body’s tissues and organs. It has also been associated with the abnormal growth and fragility of new blood vessels in the eye, which lead to the development of wet AMD. The VEGF Trap-Eye is a fully human, soluble VEGF receptor fusion protein that binds all forms of VEGF-A along with the related placental growth factor (PlGF). The VEGF Trap-Eye is a specific and highly potent blocker of these growth factors. Blockade of VEGF, which can prevent abnormal blood vessel formation and vascular leak, has proven beneficial in the treatment of wet AMD. Blocking VEGF has been shown to be effective in patients with wet AMD; and a VEGF inhibitor, ranibizumab, has been approved for treatment of patients with this condition.   About AMD Age-related macular degeneration (AMD) is a leading cause of acquired blindness. Patients with this condition can experience a loss of vision due to the development of abnormal, fragile blood vessels in the back of the eye. A particular type of AMD, called wet AMD, accounts for approximately 90 percent of AMD-related blindness. Wet AMD is the leading cause of blindness for people over the age of 65 in the U.S. and Europe. Macular degeneration is diagnosed as either dry (nonexudative) or wet (exudative). In wet AMD, new blood vessels grow beneath the retina and leak blood and fluid. This leakage causes disruption and dysfunction of the retina creating blind spots in central vision, and it can lead to blindness in wet AMD patients.   About Regeneron Pharmaceuticals Regeneron is a biopharmaceutical company that discovers, develops, and intends to commercialize therapeutic medicines for the treatment of serious medical conditions. Regeneron has therapeutic candidates for the potential treatment of cancer, eye diseases, and inflammatory diseases and has preclinical programs in other diseases and disorders. Additional information about Regeneron and recent news releases are available on Regeneron’s worldwide web site at www.regeneron.com   About Bayer HealthCare The Bayer Group is a global enterprise with core competencies in the fields of health care, nutrition and high-tech materials. Bayer HealthCare, a subsidiary of Bayer AG, is one of the world’s leading, innovative companies in the healthcare and medical products industry and is based in Leverkusen, Germany.The company combines the global activities of the Animal Health, Consumer Care, Diabetes Care and Pharmaceuticals divisions. The pharmaceuticals business operates under the name Bayer Schering Pharma AG. Bayer HealthCare’s aim is to discover and manufacture products that will improve human and animal health worldwide. Find more information at www.bayerhealthcare.com.     Forward-looking statements This news release contains forward-looking statements based on current assumptions and forecasts made by Bayer Group management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in our annual and interim reports to the Frankfurt Stock Exchange and in our reports filed with the U.S. Securities and Exchange Commission (including our Form 20-F). The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.   Source: Bayer Press Release

New Head-to-Head Study ALERT (Atazanavir or LEXIVA with Ritonavir and Truvada) Comparing Protease Inhibitors Lexiva® and Atazanavir Show Similar Efficacy and Lipid Changes in Treatment of HIV Patients

---Additional studies evaluate a lower dose of Ritonavir® for boosting Lexiva---    Sydney, Australia – July 25, 2007 – A new study comparing two protease inhibitors used in the treatment of HIV patients showed similar efficacy and lipid effects between the two drugs. The head to head study, evaluated the use of GSK’s LEXIVA® (fosamprenavir calcium) given on an open label, randomized basis to 106 antiretroviral naïve patients versus the protease inhibitor atazanavir[*] (Reyataz®). These data, from a study known as ALERT, were presented today at the 4th International AIDS Society Conference (IAS) in Sydney, Australia.   A separate study, also presented at IAS, provides additional information on the efficacy and impact on lipids of LEXIVA with a lower dose of ritonavir – 100mg instead of 200mg, once daily in treatment naïve patients. Ritonavir works with LEXIVA and other protease inhibitors to boost the medication level in the bloodstream making the protease inhibitor more effective in suppressing HIV.   LEXIVA is indicated in combination with other antiretrovirals for the treatment of HIV infections and is usually boosted with 200mg of ritonavir. A regimen of LEXIVA with a 100mg dose of ritonavir is not approved; however, it is currently being evaluated for use by the U.S. Food and Drug Administration.   ALERT Study Explained   ALERT (Atazanavir or LEXIVAwith Ritonavir and Truvada) was an open-label, randomized study of 106 patients comparing the efficacy and safety of LEXIVA/r 1400mg/100mg to atazanavir (ATV/r) 300mg/100mg, each in combination with tenofovir and emtricitabine. Antiretroviral-naïve patients were randomized to either treatment arm and received medication once daily. The study monitored changes in viral load, total cholesterol, HDL, LDL and triglycerides. At week 48, both treatment arms showed comparable viral suppression, changes in lipid levels, incidence of adverse effects, and CD-4 cell count improvements.   In the LEXIVA/r arm, 75 percent (40/53) had viral load <50c/mL and 79 percent (42/53) had viral load <400c/mL. This compared with 83 percent (44/53) [p=0.34] and 87 percent (46/53) of patients [p=0.30] taking atazanavir/r, respectively. Percent increase in median lipids at week 48 was also similar for both treatment arms. Results for the LEXIVA/r and atazanavir/r arms were, respectively: total cholesterol 11mg/dL vs. 27mg/dL, triglycerides 34mg/dL vs. 7mg/dL, HDL-cholesterol 5mg/dL vs. 11mg/dL, and LDL-cholesterol 4mg/dL vs. 4mg/dL. Mean CD4 cell count change from baseline was +170 cells/mm3 for LEXIVA/r vs. +183 cells/mm3 for atazanavir/r.   Treatment-related Grade 2-4 adverse events occurred in a similar proportion of patients in both arms with the exception of hyperbilirubinemia which occurred in 43 percent of the patients in the ATV/r arm and in none of the patients treated with LEXIVA.     Ritonavir Dosing Study Explained   This study was an open-label, randomized study in 115 antiretroviral-naïve patients that compared the effect of the 200mg boosted dose to the 100mg boosted dose on changes in regional fat mass and bone mineral density. Epzicom® (abacavir sulfate and lamivudine) was the nucleoside backbone in both groups. The primary efficacy endpoints were HIV RNA <400 copies/mL at 48 weeks and the proportion of patients who experienced drug related discontinuations at week 48 (total N = 115).    Specifically the study showed:   84 percent of the patients in the ritonavir 100mg arm compared with 67 percent of the patients in the ritonavir 200mg arm achieved HIV RNA < 400 copies/mL at week 48 (p = 0.026). Fat changes in the upper limbs for patients treated with LEXIVA/r 200mg (n=43) versus LEXIVA/r 100/mg (n=44) was 16 percent vs. 11 percent, lower limbs (14 percent vs. 9 percent) and trunk (32 percent, vs. 18 percent). Changes in fasting lipids were similar between treatment groups. Although clinically meaningful (> 20 percent) declines in arm and leg fat and increases in trunk fat occurred in both groups of patients, they occurred LESS frequently in patients treated with LEXIVA plus 100mg ritonavir once per day (difference not statistically significant). Changes in BMD were small (<1 percent) in both study arms at 48 weeks.   Overall, treatment with Lexiva/r was generally well-tolerated. The most commonly reported adverse events were Grade 1 and included diarrhea (30 percent), nausea (20 percent), and vomiting (10 percent). There were no virologic failures or discontinuations due to adverse events.     LEXIVAIndication Statement and Background   LEXIVAis indicated for the treatment of HIV infection in combination with other antiretroviral medications. The following points should be considered when initiating therapy with LEXIVA plus ritonavir (LEXIVA/r) in protease inhibitor (PI)-experienced patients: the PI-experienced patient study was not large enough to reach a definitive conclusion that LEXIVA/r and lopinavir/ritonavir are clinically equivalent. Once-daily administration of LEXIVA plus ritonavir is not recommended for PI-experienced patients.    The recommended dosing for LEXIVA is:   Therapy naïve adults LEXIVA 1400mg twice daily LEXIVA 1400mg once daily plus ritonavir 200mg once daily LEXIVA 700mg twice daily plus ritonavir 100mg twice daily Protease inhibitor experienced adults LEXIVA 700mg twice daily plus 100mg ritonavir twice daily   LEXIVA was approved by the FDA for use in the US in 2003. It is the first PI to offer flexible dosing options (for PI-naïve patients) with no food or water restrictions.   Important Safety Information about LEXIVA    HIV medicines do not cure HIV infection/AIDS or prevent passing HIV to others.    Patients should not take LEXIVA if they have had an allergic reaction to LEXIVA or AGENERASE® (amprenavir). High blood sugar, diabetes or worsening of diabetes, and bleeding in hemophiliacs have occurred in some patients taking protease inhibitors. When a patient starts taking HIV medicines, his immune system may get stronger and could begin to fight infections that have been hidden in his body, such as pneumonia, herpes virus, or tuberculosis. If a patient has new symptoms after starting his HIV medicines, he should tell his doctor. Changes in body fat may occur in some patients taking antiretroviral therapy. The cause and long-term health effects of these conditions are not known at this time. Skin rashes can occur in patients taking LEXIVA. Rarely, rashes were severe or life threatening. Opportunistic infections can develop when a patient has HIV and his immune system is weak. It is very important that patients see their healthcare provider regularly while taking LEXIVA to discuss any side effects or concerns. Most common side effects in clinical studies were diarrhea, headache, nausea, rash, and vomiting. In most cases, these side effects did not cause people to stop taking their medicine.    For full prescribing information for LEXIVA, please visit www.treathiv.com .    LEXIVA was co-discovered by GlaxoSmithKline and Vertex Pharmaceuticals Incorporated.    About GlaxoSmithKline   GlaxoSmithKline is one of the world’s leading research-based pharmaceutical and healthcare companies and an industry leader in HIV research and therapies. The company is engaged in basic research programs designed to investigate new targets to treat HIV. For full prescribing information please go to www.LEXIVA.com.   GSK’s Bridges to Access program can help provide qualified individuals with access to GSK’s antiretroviral medications, as well as help identify insurance or other support for medications. Patients may be eligible for this program if they are not eligible for prescription drug benefits through any other private or public insurer, payer or program. In 2004, GlaxoSmithKline donated more than $372.5 million worth of prescription drugs to 475,000 patients. For more information, visit www.bridgestoaccess.gsk.com or call 1-866-PATIENT.     About Vertex   Vertex Pharmaceuticals Incorporated is a global biotechnology company committed to the discovery and development of breakthrough small molecule drugs for serious diseases. The Company’s strategy is to commercialize its products both independently and in collaboration with major pharmaceutical companies. Vertex’s product pipeline is principally focused on viral diseases, inflammation, autoimmune diseases and cancer. Vertex co-discovered the HIV protease inhibitor, LEXIVA, with GlaxoSmithKline.      [*]Atazanavir is known by the trade name Reyataz® and is made by Bristol-Myers Squibb.

Roche and Toyama Chemical Enter Licensing Agreement to Develop Potential Breakthrough Drug to Treat Rheumatoid Arthritis Novel Agent

----T-5224 may block the progressive destruction of joint and bone----   Basel, 25 June 2007----Toyama Chemical Co., Ltd. and Roche announced today that they have entered into a licensing agreement for the worldwide research, development and commercialization of Toyama Chemical’s novel oral rheumatoid arthritis agent T-5224. By inhibiting a specific inflammatory process, T-5224 has the potential to block signs and symptoms of rheumatoid arthritis as well as the progressive destruction of joint and bone. T-5224 is currently in phase I. With this partnership, Roche is further strengthening its promising portfolio and R&D pipeline in the area of rheumatoid arthritis.   "This novel oral compound complements Roche’s developing portfolio of drug candidates in inflammation and rheumatoid arthritis. The agent T-5224 has the potential to inhibit a key trigger of rheumatoid arthritis and has already shown promising pharmacological efficacy and safety in early clinical studies," said Jean-Jacques Garaud, Head of Roche Pharma Development. "Our new collaboration is good news for all patients with rheumatoid arthritis as well as for our two companies. We are looking forward to collaborating with our new colleagues in Japan to develop T-5224."   "By entering into a research and development collaboration with Roche, one of the world’s leading research and development companies, we are able to increase Toyama’s potential for novel drug development in the anti-inflammatory field, which is a field of concentration for Toyama Chemical," said Masuji Sugata, President of Toyama Chemical.   Under the terms of the agreement, Toyama Chemical has granted Roche exclusive rights to research, develop, and sell T-5224 worldwide excluding Japan where Toyama Chemical will retain exclusive rights. The agreement also encompasses the joint research and development of back-up candidates to T-5224. Toyama Chemical will receive upfront payments and milestone payments totalling up to 370 million US dollars, based on certain development and commercial milestones. If approved for marketing, Toyama Chemical will receive royalties based on the net sales of T-5224 by Roche.   About T-5224 T-5224 is an inhibitor of the transcription factor AP-1 (Activator Protein-1) which is known to play an important role in the pathology of rheumatoid arthritis. AP-1 turns on a variety of genes in response to inflammation triggers, including many that are responsible for the proteins that are the targets of current rheumatoid arthritis products. In addition, in joint cells called osteoclasts, AP-1 stimulates the production of enzymes that are thought specifically to cause the destruction of bones and joint tissue. Therefore, by inhibiting the AP-1 process, T-5224 affects several key pathways and may prevent the progression of this disabling disease in many patients.   T-5224 was first identified as a drug candidate in rheumatoid arthritis through collaboration between Toyama Chemical Research and Professors Shunichi Shiozawa of Kobe University and Shuichi Hirono of Kitasato University. Non-clinical studies were completed through this collaboration and Phase I studies have been carried out in Japan since June of last year. Toyama Chemical is receiving, through the Contract Development Program, support from the Japan Science and Technology Agency, an independent administrative institution, for its research and development in Japan.   About rheumatoid arthritis Rheumatoid arthritis (RA) is a progressive, systemic autoimmune disease characterized by chronic inflammation of multiple joints and fatigue as well as the possibility of osteoporosis, anaemia, and lung, skin and liver effects. This inflammation causes pain, stiffness and swelling, resulting in loss of joint function due to destruction of the bone and cartilage, often leading to progressive disability. Further, as chronic inflammation continues, there may be shortening of life expectancy as a result of effects on major organ systems. After 10 years, less than 50% of patients can continue to work or function normally on a day to day basis. RA affects more than 21 million people worldwide.   About Roche in rheumatoid arthritis One of the most important drivers for growth at Roche over the next few years is expected to be the company’s emerging franchise in autoimmune diseases with rheumatoid arthritis as the first indication. Following the launch of MabThera (rituximab) there are a number of projects in development, potentially allowing Roche to build on further opportunities. MabThera is the first and only selective B-cell therapy for RA, providing a fundamentally different treatment approach by targeting B cells, one of the key players in the pathogenesis of RA. Actemra is Roche’s second novel medicine and is a humanised monoclonal antibody to the interleukin-6 (IL-6) receptor, inhibiting the activity of IL-6, a protein that plays a major role in the RA inflammation process. Actemra is the result of research collaboration by Chugai and is being co-developed globally with Chugai. Additional projects creating a rich pipeline include compounds in Phase I, II and III clinical trials. Notably, ocrelizumab, a fully humanised anti-CD20 antibody, is just entering phase III development for RA.   About Toyama Chemical Toyama Chemical specializes in research and development, and strives to contribute to the further development of global health care through new drug development. Toyama concentrates its R&D in three fields: anti-infective agents, anti-inflammatory agents, and cerebral function improvers and cardiovascular drugs. Pharmaceuticals now in the pipeline include T-3811, a synthetic antibacterial agent; T-614, an oral anti-rheumatic agent; and T-817MA, a treatment for Alzheimer's disease. The company has formed strategic partnerships with domestic and overseas pharmaceutical manufacturers as well as establishing clinical research subsidiaries in the U.S. and U.K. Validation of Toyama’s success can be found in their technology exports and their royalty income which is the highest among mid-sized Japanese pharmaceutical companies. Toyama is taking an aggressive, outward-looking approach, globalizing its activities with the aim of becoming a key pharmaceutical manufacturer. Additional information about the Toyama Chemical is available on the Internet at www.toyama-chemical.co.jp/eng.   About Roche Headquartered in Basel, Switzerland, Roche is one of the world’s leading research-focused healthcare groups in the fields of pharmaceuticals and diagnostics. As the world’s biggest biotech company and an innovator of products and services for the early detection, prevention, diagnosis and treatment of diseases, the Group contributes on a broad range of fronts to improving people’s health and quality of life. Roche is the world leader in in-vitro diagnostics and drugs for cancer and transplantation, a market leader in virology and active in other major therapeutic areas such as autoimmune diseases, inflammation, metabolism and central nervous system. In 2006 sales by the Pharmaceuticals Division totalled 33.3 billion Swiss francs, and the Diagnostics Division posted sales of 8.7 billion Swiss francs. Roche employs roughly 75,000 worldwide and has R&D agreements and strategic alliances with numerous partners, including majority ownership interests in Genentech and Chugai. Additional information about the Roche Group is available on the Internet at www.roche.com.     Source: Roche Press Release

Optaflu®, the Novartis Cell Culture-Derived Influenza Vaccine, Receives Positive Opinion

---Novartis leading the introduction of influenza cell culture manufacturing - the first major innovation in influenza vaccine manufacturing in more than 50 years---   ---Optaflu® to help meet growing need for seasonal influenza vaccines, production technology has potential for quick scale-up in case of an influenza pandemic--   ---Novartis proprietary cell culture technology offers possibility to obtain a better matched vaccine with circulating viruses than currently available technology---   Basel, April 27, 2007 - Novartis has received a positive opinion supporting European Union approval of its cell culture-derived seasonal influenza vaccine Optaflu®, which is aiming to become the first influenza vaccine to utilize a mammalian cell line, rather than chicken eggs, for antigen production.   The Committee for Medicinal Products for Human Use (CHMP), which reviews applications for all 27 countries in the EU as well as Iceland and Norway, has recommended approval of this new vaccine. The European Commission generally follows the recommendations of the CHMP and delivers its final decision within two to three months.   "Novartis Vaccines is pleased with this positive recommendation for Optaflu, the first cell culture-derived influenza vaccine and the first major innovation in influenza vaccine manufacturing in more than 50 years," said Dr. Jörg Reinhardt, CEO of Novartis Vaccines and Diagnostics. "Optaflu contributes to meeting the growing demand for seasonal influenza vaccines, and this production technology offers the potential for quick scale-up of manufacturing in the event of an influenza pandemic."   A submission is anticipated in 2008 for US regulatory approval of this cell culture-derived seasonal influenza vaccine.   More than 3,400 people received Optaflu during the clinical development program evaluating the vaccine's safety and immunogenicity. Data reviewed by CHMP from the clinical program showed Optaflu fulfilled all of the Committee's immunogenicity criteria.   The data further showed the cell culture-derived influenza vaccine was comparable to conventional egg-based vaccines in efficacy and tolerability. Additives, such as antibiotics, are avoided in the Optaflu production process. Additionally, people allergic to eggs and egg products can benefit from receiving this vaccine since it is created without egg proteins. Like established conventional egg-based vaccines, Optaflu is administered via intramuscular injection. Data from the Phase III clincial program were presented at the Influenza Vaccines for the World Congress (IVW) meeting in October 2006.   About cell culture technology and the Novartis proprietary cell line   Cell culture manufacturing is the first major innovation in influenza vaccine manufacturing in more than 50 years. It represents a new approach to vaccine production whereby influenza virus is propagated in readily available mammalian cell lines rather than in chicken eggs.   Virus cultivation utilizing the Novartis proprietary cell line as an exclusive host offers the possibility of more robust virus proliferation since most circulating viral strains are unable to replicate in chicken eggs. In a next generation of products, it also offers the possibility for vaccine seed strain development that more closely matches the original "wild" virus because cell culture technology eliminates the need for passage through eggs where the virus may be forced to adapt in order to replicate. As a result, the antigen included in the vaccine may express more authentically the surface of the wild type virus, potentially translating into a better immunogenic and effective response.   The Novartis proprietary cell culture technology enables flexible, faster start-up of vaccine manufacturing. With the advent of this technology, Novartis Vaccines is contributing  to meet the growing need for seasonal influenza vaccines and quickly respond to a potential pandemic influenza threat.   About influenza and pandemic influenza   Influenza can cause mild to severe illness and at times can lead to death. Worldwide, influenza epidemics result in approximately 250,000 to 500,000 deaths each year[1]. Influenza-related complications can include pneumonia and dehydration, and worsening of chronic conditions, such as congestive heart failure, asthma, or diabetes[2]. The World Health Organization (WHO) and its Global Influenza Surveillance Network recommend vaccination as the principal method for preventing influenza[1].     Increased circulation of avian influenza A/H5N1 virus has been documented in Asia and Europe. On a pandemic threat scale of one to six, the World Health Organization currently ranks the H5N1 risk at phase three. This virus is highly contagious in chickens, adding the possibility that a pandemic strain could emerge at a time when egg supplies are lower than usual due to a previous epidemic in chickens. Novartis proprietary cell culture line offers an alternative to traditional egg-derived vaccines.   References 1. World Health Organization "Influenza Fact Sheet" http://www.who.int/mediacentre/factsheets/fs211/en/index.html Accessed October 10, 2006   2. Centers for Disease Control and Prevention (CDC) "Questions & Answers: The Disease" http://www.cdc.gov/flu/about/qa/disease.htm  Accessed October 10, 2006     Disclaimer This release contains certain forward-looking statements, relating to the Novartis Group's business, which can be identified by the use of forward-looking terminology such as "to help," "potential," "possibility," "aiming to", "recommended", "generally follows the recommendations," "anticipated," "potentially, "can," "could," or similar expressions, or by express or implied discussions regarding potential marketing approvals or future sales of Optaflu. Such forward-looking statements reflect the current views of Novartis regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results with Optaflu to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that Optaflu will be approved for any indications in any market or that Optaflu will reach any particular sales levels. In particular, management's expectations regarding Optaflu could be affected by, among other things, unexpected regulatory actions or delays or government regulation generally; unexpected clinical trial results, including additional analysis of existing clinical data and new clinical data; competition in general; the ability of Novartis to obtain or maintain patent or other proprietary intellectual property protection; increased government, industry, and general public pricing pressures; and other risks and factors referred to in the Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.   About Novartis Novartis Vaccines and Diagnostics is a division of Novartis focused on the development of preventive treatments and tools. Novartis Vaccines is the world's fifth-largest manufacturer and second-largest supplier of influenza vaccines in the US. The division's products also include meningococcal, pediatric and travel vaccines. Chiron, the blood testing and molecular diagnostics business, is dedicated to preventing the spread of infectious diseases through the development of novel blood-screening tools that protect the world's blood supply. For more information, please visit http://www.novartisvaccines.com.   Novartis AG (NYSE: NVS) is a world leader in offering medicines to protect health, cure disease and improve well-being. Our goal is to discover, develop and successfully market innovative-products to treat patients, ease suffering and enhance the quality of life. We are strengthening our medicine-based portfolio, which is focused on strategic growth platforms in innovation driven pharmaceuticals, high-quality and low-cost generics, human vaccines and leading self-medication OTC brands. Novartis is the only company with leadership positions in these areas. In 2006, the Group's businesses achieved net sales of USD 37.0 billion and net income of USD 7.2 billion. Approximately USD 5.4 billion was invested in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 100,000 associates and operate in over 140 countries around the world.   For more information, please visit http://www.novartis.com

Market Intelligence and Pharma Data Mining e-Published, Feb 1st, 2007  By Dr. Krishan Maggon,  Ph.D., Pharmaceutical Biotechnology R&D Advisor ICC- Route de Pré Bois 20, PO Box 1887, 1215 GENEVA 15, Switzerland, Email: maggonk@yahoo.com   Abstract Biomedical journals have recently published several market analysis covering new drugs and sales data for rheumatoid arthritis, influenza vaccines, monoclonal antibodies and recombinant protein therapeutics derived from commercial databases. This paper will revisit and analyse some of the published sales and market data. Authors from firms selling commercial data bases to pharmaceutical and biotechnology industry present their own market data, sales forecast and identify brands, which will drive future growth and markets. Comparison of the sales figures of blockbuster medicines from company sources and commercial reports and databases reveals significant discrepancies. Three Datamonitor papers in 2006 provide different sales and forecast for influenza vaccines. Comparison data from different sources and projections from previous reports or forecasts with actual data is rarely presented or discussed. Such discrepancies may result in a misleading evaluation of product, markets, portfolio, research development and company. Biomedical publications should develop a new policy and apply the same high standards of data reporting as in regular publications for commercial data sources.   Introduction Market intelligence, consultancy and knowledge providers to the pharmaceutical, biotechnology, device and diagnostic industry, had total global sales of $6 billion in 2005. Each year commercial data firms issue hundreds of research reports costing thousands of dollars each and 2007 will be the same. These reports cover global best selling medicines, new drugs and market analysis of selected therapeutic area. It is claimed that these exclusive research reports identify drivers of future growth and market size forecasts that drive decisions and shape strategies by executives. IMS with 2005 sales of $1.8 billion has a 30% market share and its global data, figures, graphs for top selling medicines are extensively covered in several popular news, financial, business, scientific and medical media thereby having a 100-fold multiplier impact factor as a yearly ritual. Similarly Ernst & Young, Accenture, IBM, Boston Consultancy, Price Waterhouse Cooper, Scrip, Reuters, Thompson-ISI and Datamonitor reports are quoted and reported extensively in new and old media. Unlike IMS, other data-mining firms do not report income/sales from pharmaceutical and biotechnology companies.   In addition to industry, hedge funds, venture capital, investment funds, industry specific funds, leading banks and traders use these reports and data to make decisions about trade, investment and profits. All major pharmaceutical and biotech companies in the world are customers of such reports and data.   The advantage of these reports is that they provide a comprehensive list of blockbuster drugs, sales and companies involved and market trends. The disadvantages are the high cost of these reports, somewhat outdated data, confidential nature of the data collection and evaluation and divergence of sales figures in comparison with company reports. All commercial databases take shelter behind the safe harbor statement “their models and methodologies for estimation of sales figures may give results which may differ from actual results”. Company annual and quarterly reports and presentations provide easy access to real data for their top selling products. The disadvantage is that some European and Japanese companies still do not provide sales data for their best selling products and use a different financial year than the calendar year.   Global Sales Data   Forecasting and predicting the future markets and trends for pharmaceuticals and monitoring the actual market sales remains an important tool for the industry to plan its growth, R&D and marketing strategy.  Several commercial reports cover global blockbuster drug sales and R&D trends (1-4) (Table 1). Differences of over $1 billion were observed for the top 1-2 brands and 0.5 billion for several brands (1-4) since 2002.  The ranking of best selling brands and growth rates were significantly different. Ranking of the companies based on sales of biologic drugs, R&D expenses and R&D budgets was different as well (5-8) (Tables 2, 3).       Table 1.  Global Pharmaceutical and Biotechnology Market  2005-2006 ($ Billion)            Global Pharmaceutical Market  IMS Health         2005                603   Global Biotechnology Market  Ernst & Young      2005                63                                                          Datamonitor                                      40                                                    IMS                                                  52             Leading therapeutic categories in 2005   Pharmaceuticals Market size Biotechnology Protein Market size CNS 91 Anemia Erythropoietin 12.3 Cardiovascular 85 Immuno Inflammatory TNF Blockers 8.6 Infections 58 Diabetes Insulin 7.2 Obesity 35 MS+ Hepatitis C Interferon 6.8 Cancer 30 Cancer, Arthritis Infection Monoclonal Antibodies 14 Ulcer 27 Infections Vaccines 14 Diabetes 20 Growth, fertility Hormones 5   IMS Top Line Industry Data 2005; Ernst & Young 2006 Beyond Borders Maggon K. R&D Paradigm Shift & billion dollar biologics. In Shayne C. Gad Ed. Handbook of Pharmaceutical Biotechnology. John Wiley, New York. 2007. In Press       Table 2.   Top Companies Sales of Biologics in 2005   Company Sales $ billion 2005                             Major Product Sale $ billion 2005                              Amgen 13 Enbrel 3.7, Aranesp 3.3 Roche 9.3 Rituxan 3.2, Herceptin 1.7 J&J 6.8 Remicade 3.5, Procrit 3.3 Novo Nordisk 4.2 Novolin, analogs 3.6 Lilly 3 Humulin, Humalog 2.1 Merck Serono 2 Rebif 1.3 Bayer Schering 2 PegIntron 1.4 Genzyme 2 Cerazyme 0.93 Baxter 1.8 r Proteins 1.2 Biogen Idec 1.5 Avonex 1.2 Wyeth 1.5 Prevanar 1.5 Sanofi Aventis 1.4 Lantus 1.4 Abbott 1.4 Humira 1.4 Schering Plough 1.4 Remicade 0.9 MedImmune 1.2 Synagis 1.1     Table 3. Top Brand Human Medicines in 2005 Generic Name Brands Companies Indications 2005 Sales $ billion Company   IMS     Diff Atorvastatin Lipitor Pfizer Cholesterol 12.2          12.9      +0.7 Clopidrogel Plavix Bristol Myers Squibb, Sanofi Aventis Atherosclerosis 6.2             5.9        -0.3        Fluticasone Salmetrol Advair Glaxo Smith Kline Asthma 5.5             5.6       +0.1 Amlodipine Norvasc Pfizer Hypertension 4.76           5.0      +0.24 Esomaprazole Nexium AstraZeneca Ulcers 4.63           5.7      +1.07 Simvastatin Zocor Merck Cholesterol 4.4             5.3       + 0.9 Glanzapine Zyprexa Lilly Schizophrenia 4.2             4.7        +0.5 Pentoprazole Protonix Atlanta, Wyeth Ulcers 4.0             NA Lansoprazole Prevacid Takeda, Abbott Ulcers 3.8             4.0       + 0.2 Valsartan Diovan Novartis Hypertension 3.67            NA Risperidone Risperdal J&J Schizophrenia  3.55           4.0     +0.45 Venlafaxine Effexor Wyeth Depression 3.5              3.8      + 0.3 Sales as reported by company’s annual results/reports. The IMS figures for 2005 are included if available.      IMS (1) and Ernst & Young (2) sales figures for pharmaceutical and biotechnology are considered Industry gold standard and are widely used.  IMS data for top selling global brands differs significantly from sales data reported by companies for the same year (Table 3). The differences of more than $1 billion and $ 0.5 billion for some brand were observed without any clear explanation or rationale. IMS figures for Lipitor sales in 2003 were $1 billion more than reported by Pfizer. Review of sales figures released by companies (6,7) producing medicines with sales in excess of $3 billion in 2004 (15 compounds in total), shows that the IMS figures differed by as much as $ 1 billion for two drugs (Lipitor and Nexium) and over $ 0.5 billion another four drugs in the year 2003 and two drugs in 2004. Differences in IMS values and company sales figures of less than $200 million was seen for only 2 drugs in the past  three years (Table 3). Variables like exchange rates, bulk discounts, Stockpiling, Parallel imports, Damages/returns and exclusion of certain developing countries may be contributing factors in data collection by IMS and companies may explain small differences of a few million dollars. Such differences were first reported by the author in 2003 for the year 2002 sales data and have persisted (5-7).               TNF Antagonists The market data presented for TNFα antagonists 2005 sales was included in a recent paper (9) covering rheumatoid arthritis drugs and markets published in March 2006. The companies (Amgen, Johnson & Johnson, and Abbott) had released their yearly earnings and top brand sales by last week of January 2006. The paper mentions a total market for the TNFα antagonists as more than $6 billion, the actual figure as reported by companies was $5.5 billion in 2004 and $8.6 billion in 2005 (Enbrel $ 3.7 billion, Remicade $ 3.5 billion, Humira $ 1.4 billion). Combined sales of Enbrel and Remicade are 83% and closer to the 80% of the total TNFα market mentioned in the paper (9). Only one monoclonal antibody in Phase III (Cimzia, UCB) for which NDA has been filed is mentioned. Twenty other monoclonal antibodies in Phase III trials in arthritis patients are not mentioned? The article fails to provide an updated 2005 sales or development status of Phase III/NDA projects in rheumatoid arthritis. There is a real need for a new agent, which in combination with methotrexate and TNFα antagonists will increase sustained response rate without increasing risk of infections or other cardiovascular adverse reactions (10-12). The success of future agents will depend on the real therapeutic gain achieved with $25000 annual cost and the ability of healthcare systems to cover all arthritis patients.  Monoclonal Antibodies Reichert and Pavlou (9) analysis of the monoclonal antibody market in 2004 predicted the monoclonal antibody market to $16.7 billion in 2008, the combined sales of the top selling therapeutic monoclonal antibodies in 2005 were $14 billion as reported by companies. This figure excludes antibodies used for diagnostic tests and procedures. Datamonitor (14-17) projected figures for 2008 were reached in 2006 with sales of $18 billion. The sales figures for Avastin were $ 500 million lower than the actual sales figures reported by Roche for 2005 and for Erbitux higher by $ 140 million. With over 200 companies developing monoclonal antibodies and the total number of active projects in R&D and clinical development at 132 seems to be lower than the real figure (17-20). FDA approved only one monoclonal antibody Orencia in 2005 and  two Lucentis and Vectibix in 2006.   Influenza Vaccines   Two recent 2006 Datamonitor articles on influenza vaccine provide divergent sales and forecast. One article reports 2004 sales of $1.3 billion and a 2010 forecast of $3.7 billion (21), and another $1.1 billion sales and $3.1 billion forecast  (22). A news story (23) about Datamonitor Influenza vaccine reports 2005 sales of $1.6 billion and a 2010 forecast of $3.0 billion (Table 4). Concerns about avian influenza and stockpiling by governments and the strong demand for influenza vaccines in 2006 were offset by mild influenza winter resulting in oversupply of the vaccine in USA and Europe.  If influenza vaccines accounted for 14% of total vaccine sales, the global market for vaccines was $14 billion in 2005.  Five top vaccine companies (Glaxo Smith Kline, Sanofi- Aventis, Merck, Wyeth and Chiron) (24) had combined sales of $8.6 billion in 2005. Table 4. Influenza Vaccine Sales and Forecast   Sales  $  billion   2004                2005                2010 forecast                           Reference --------------------------------------------------------------------------------------------- 1.2                   1.8                   NA                                          Company* 2005 Annual report Datamonitor Report 2006   1.3                   NA                  3.7                                           8   1.1                   NA                  3.1                                           9   NA                  1.6                   3.0                                           10 ________________________________________________________________   * Sanofi Aventis, Glaxo Smith Kline, Merck,    Chiron-Novartis, Solvay, Crucell-Berna, MedImmune   Therapeutic Proteins Datamonitor (4, 25, 26) market analysis and forecasting methodology has been described. Once again the global market growth projections for therapeutic proteins from 2004 to 2010 are provided. The market for 2005 was estimated at $40 billion and for 2010 at 50 billion. IMS (1) data gave a figure of $ 52 billion and Ernst & Young (2) of $ 63 billion (Table 1). The sales of the top 20-biotechnology products (20) were $59.6 billion and assuming that these products account for 75% of the total market, the total market value is near $75 billion for 2005. Similar results are obtained if total sales of different therapeutic categories are added (Table 1). The listed brands driving future markets25 and growth missed out on several current blockbuster brand like Synagis, Rituxan, Herceptin, Prevanar, Copaxone, Avastin and blood factors (5).                Discussion   Variables like exchange rates, bulk discounts, stockpiling, parallel imports, damages/returns and exclusion of certain developing countries cited as contributing factors in data collection by commercial firms may explain small differences of a few million dollars. There is no logical explanation for differences of $500-1000 million in the same year for some best selling global brands or R&D expenses of top research driven companies. Such differences were first reported in 2003 for the year 2002 sales data and have continued (1-4). In the era of Global Accounting Standards and SEC requirements, company-reporting standards are well known and more reliable while commercial data collection methods remain confidential. Commercial firms have failed so far to correct the deficiencies in their methodology and require constant improvements to eliminate and minimize differences. Publications in biomedical journals of such reports as regular or invited features with significant discrepancies, missing data and lack of comparative data require new editorial policy and guidelines.   Commercial research reports and sales figures differ significantly in comparison to companies’ annual reports. The data, trends and predictions may significantly impact market value of companies, R&D projects, licensing, merger and acquisition, joint ventures, alliances and deals. Similarly ranking of companies by sales, profitability, R&D budgets, new blockbuster drugs may change market value, perceptions and cost of  loans or new funds for companies.   Since commercial reports are used for strategic decision-making, it is obvious that significant discrepancies in sales data, market projections may contribute to the market failure of some new drugs and decline in R&D productivity and current low public perception of the pharmaceutical industry. Significant variations in past predictions concerning present trends and markets forecasts have been observed. The data mining firm’s recent data should match or come closer to company’s latest annual reports for top selling global brands, sales growth, R&D budgets and total market size in different indications.  Significant and persistent discrepancies in data from different sources will ultimately undermine the current reliance of industry on commercial data and research reports.   It is relatively difficult to publish an article challenging big commercial firms. The present article challenges commercial research report figures, marketing and growth forecast and future trends published in selected biomedical journals. Editors of journals when contacted about discrepancies in data decided to ignore the differences and not publish the corrections. One editor decided that an article pointing out data differences was not worth publishing as it did not go beyond discrepancies. When additional comments were added, the editor decided that the article was not balanced and must include positive aspect of commercial research reports.   There is no independent comparative evaluation of past predictions and actual results or any oversight by regulators or SEC for commercial reports. In the era of Global Accounting Standards and SEC requirements, company-reporting standards are well known and more reliable while commercial data collection methods remain confidential. The sales projections for the same product for any year should converge for all validated methods for data collection, forecast and analysis.   References   1.      IMS Top Line Global Industry Data (2005). www.imshealth.com, http://www.ims-global.com/insight/insight.htm 2.      Ernst & Young. (2005 & 2006). Global Biotech Report and Global Pharmaceutical Trends. Levinson A.D. (2005). What distinguishes biotech from big pharma? Global Industry Perspectives. 3.      Reuters Health. Reports (2004) The Pharmaceutical Market Outlook to 2010. http://www.reutersbusinessinsight.com/content/rbhc0091t.pdf. 4.    Datamonitor Potential blockbuster drugs (2004). www.datamonitor.com 5.      Gray N. (2006). Changing Landscape The World top 50 Pharmaceutical Companies. Pharmaceutical Exec. 26, 78-101.   6.      Maggon K. R&D paradigm shift and billion dollar biologics. In Handbook of Pharmaceutical Biotechnology. Ed Gad, S. C. John Wiley, New York. 2007 In Press 7.      Maggon K. The ten billion dollar molecule. Pharmaceutical Executive, 23, 60-68, 2003. 8.    Maggon K. Best Selling Human Medicines 2002-2004. Drug Discovery Today, 10, 738-742 (2005).   9.      Moreland, L.,Bate G. & Kirkpatrick, P. Abatacept. Nature Reviews. 5. 185-186(2006). 10.  Sesin, C. A. & Bingham, C. O. Remission in Rheumatoid Arthritis: Wishful Thinking or Clinical Reality? Seminars in Arthritis and Rheumatism, 35, Issue 3, 185-196 (2005). 11.  Hochberg, M. C. et al. The Benefit/Risk Profile of TNF-Blocking Agents: Findings of a Consensus Panel. Seminars in Arthritis and Rheumatism, 34, 819-836(2005). 12.  Miossec P. Therapeutic targets in rheumatoid arthritis: More to come but which one(s) to select? Drug Discovery Today: Disease Mechanisms, 2, 327-330 (2005). 13.  Reichert J. M.& Pavlou A. K. Monoclonal Antibody Market. Nature Reviews 3, 383-384, (2004). 14.  Evans, D. & Das, R. Monoclonal Antibodies : evolving into a $ 30 billion market. Datamonitor Report. (2005). 15.  Reichert J. M. et al. Monoclonal antibodies success in the clinic. Nature Biotechnology. 23, 1073-1078 (2005). 16.  Pavlou, A. K. & Belsey, M. J. The therapeutic antibodies market to 2008  Eur J Pharmaceut Biopharmaceut., 59, 389-396 (2005). 17.  Scannes, L.& Branca, M. A. The evolving market for monoclonal antibodies : Facing new opportunities and pitfalls. Pharmaweek 1-23 (2006). http://www.pharmaweek.com/Exclusive_Content/2_23%20test.asp 18.   Baker, M. Upping the ante on antibodies. Nature Biotechnology  23, 1065 - 1072 (2005). 19.  Liossis, S. N.C. & Tsokos, G. C. Monoclonal antibodies and fusion proteins in medicine.  J Allergy Clin Immunol. In Press, Corrected Proof, Available online 1 September 2005. 20.  Qu, Z.et al. Development of humanized antibodies as cancer therapeutics.  Methods, 36, 84-95 (2005). 21.  Belsey M. J. et al. Influenza Vaccines. Nature Reviews. 5, 183-184, 2006. 22.  Belsey M. et al. (2006). Growth Drivers and resistors of the influenza market: The importance of cell culture flu. J. Commerc. Biotechnol. 12, 150-155. 23.  Datamonitor report (2006). Pandemic threat reignites influenza vaccine market. Webbolt. April 20, 2006. webbolt.ecnext.com. 24.  Quigley, E.(2006). Influenza therapies: vaccines and antiviral drugs. Drug Discovery Today 11, 478-480. 25.   Pavlou A. K. & Reichert, J. M. Recombinant protein therapeutics—success rates, market trends and values to 2010. Nature Biotechnology  22, 1513 – 1519 (2004). 26.  Pavlou A.K. The immunotherapies markets, 2003–2008 Journal of Commercial Biotechnology, 10, 273-278 (2004).   * Please reference or credit any material, article, table or figure cited from http://www.medicineandbiotech.com as: Copyright 2004-2007. MedicineandBiotech.com, http://www.medicineandbiotech.com/

In Interests of Patient Safety, Pfizer Stops All Torcetrapib Clinical Trials; Company Has Notified FDA and is in the Process of Notifying All Clinical Investigators and Other Regulatory Authorities

Decision Based on Recommendation Received Today of Independent Data Safety Monitoring Board for ILLUMINATE Trial; Pfizer Will Discontinue Development of Compound   Pfizer Reaffirms Financial Guidance into 2009   Pfizer to Accelerate Timetable for Transformation of Operations; Will Invest in Diverse Range of Pipeline and External Opportunities     NEW YORK, Dec. 2 /PRNewswire-FirstCall/ -- Pfizer Inc said that in the interests of patient safety it is stopping all torcetrapib clinical trials and that it has informed the Food and Drug Administration. The Company is in the process of notifying all clinical investigators in the program as well as other regulatory authorities.   The Company was informed today that the independent Data Safety Monitoring Board (DSMB) monitoring the ILLUMINATE morbidity and mortality study for torcetrapib recommended terminating the study because of an imbalance of mortality and cardiovascular events.   The Company has terminated ILLUMINATE and is in the process of asking all clinical investigators conducting trials in this development program to inform patient participants to stop taking the study medication immediately. The Company has also ended the development program for this compound.   Dr. Philip Barter, Director of the Heart Research Institute in Australia and Chairman of the Steering Committee overseeing the ILLUMINATE study, said, "Based on all the evidence we have seen regarding torcetrapib and in light of prior study results, we were very surprised by the information received from the DSMB, the only body with access to the unblinded safety data. We believed that the study was coming along as expected, and this new information was totally unexpected and disappointing, given the potential benefits of this drug."   Pfizer's Chief Executive Officer Jeffrey B. Kindler said, "While the DSMB information we received today was both surprising and disappointing, our focus is on the best interests of patients and making sure all this information is communicated to appropriate medical and regulatory authorities as quickly as possible.   "With regard to our business, we understand the challenge that this represents and we will respond quickly and aggressively to it. It is important to put this information in the context of both our commitment to transform Pfizer and our overall product and financial strength," Mr. Kindler added.     He emphasized three key points:      * First, Pfizer has a broad and diverse in-line and new product      portfolio, as well as substantial operating and financial strength.      Our financial guidance for 2006 is unchanged.  As well, we continue to      forecast revenues in 2007 and 2008 that are comparable to 2006, a      return to revenue growth in 2009, and high single-digit average growth      in adjusted diluted EPS(1) over the next two years.  We will further      enhance total returns to shareholders through dividends and share      purchases.      * Second, Pfizer's previously announced plan for transforming the company      will now be accelerated.  Pfizer will focus on its core research and      development, manufacturing and commercial operations, as well as      procurement and other areas, to improve efficiency and lower its costs      as expeditiously as possible.      * Notwithstanding the acceleration of the Company's transformation,      Pfizer's substantial financial strength will enable it to continue to      invest in a wide range of pipeline opportunities across a diverse range      of therapeutic areas, capitalizing on the largest pipeline in its      history. It will bring forward these major new product opportunities as      aggressively as possible.  In addition, Pfizer will bring increased      focus and emphasis to its business development and licensing efforts in      order to identify new products and technologies that will supplement      its pipeline.  As a result, Pfizer continues to target the introduction      of about six new products a year starting in 2010. It is important to note that in the ILLUMINATE trial, Lipitor was used as a comparator for safety and efficacy. It is the most studied statin in reducing cardiovascular outcomes. "The only reason the study was stopped early was due to the torcetrapib data. The ILLUMINATE Steering Committee wants to reassure physicians and patients that nothing in today's information has any impact on the safety or efficacy of Lipitor whatsoever," said Dr. Barter.   DISCLOSURE NOTICE: The information contained in this document and the attachment is as of December 2, 2006. The Company assumes no obligation to update any forward-looking statements as a result of new information or future events or developments.   This document and the attachment contain forward-looking information that involves substantial risks and uncertainties about the Company's in-line products and product candidates, financial results and estimates, and business prospects. Among other things, this document and the attachment contains, in particular, forward-looking information that involves substantial risks and uncertainties about improvements in the Company's research and development productivity and about various products in development and potential additional indications for various in-line products, including their potential benefits and, in certain cases, projections with respect to their advancement within the research and development pipeline, regulatory authority filing and approval dates and launch dates. You can identify these statements by the fact that they use words such as "will," "anticipate," "estimate," "expect," "project," "intend," "plan," "believe," "target," "forecast" and other words and terms of similar meaning. Among the factors that could cause actual results to differ materially are the following: the uncertainties inherent in research and development activities; decisions by regulatory authorities regarding whether and when to approve drug applications and supplemental drug applications that have been or may be filed for such products in development and for such additional indications for in-line products as well as their decisions regarding labeling and other matters that could affect the availability or commercial potential of such products and such additional indications; the speed with which regulatory authorizations, pricing approvals and product launches may be achieved; competitive developments, including with respect to competitor drugs and drug candidates that treat diseases and conditions similar to those treated by our drugs and drug candidates; the ability to successfully market both new and existing products domestically and internationally; difficulties or delays in manufacturing; trade buying patterns; the ability to meet generic and branded competition after the loss of patent protection for our products or competitor products; the impact of existing and future regulatory provisions on product exclusivity; trends toward managed care and health care cost containment; possible U.S. legislation or regulatory action affecting, among other things, pharmaceutical pricing and reimbursement, including under Medicaid and Medicare, the importation of prescription drugs that are marketed outside the U.S. and sold at prices that are regulated by governments of various foreign countries, and the involuntary approval of prescription medicines for over-the-counter use; the potential impact of the Medicare Prescription Drug, Improvement and Modernization Act of 2003; legislation or regulations in markets outside the U.S. affecting product pricing, reimbursement or access; contingencies related to actual or alleged environmental contamination; claims and concerns that may arise regarding the safety or efficacy of in-line products and product candidates; legal defense costs, insurance expenses, settlement costs and the risk of an adverse decision or settlement related to product liability, patent protection, governmental investigations, ongoing efforts to explore various means for resolving asbestos litigation and other legal proceedings; the Company's ability to protect its patents and other intellectual property both domestically and internationally; interest rate and foreign currency exchange rate fluctuations; governmental laws and regulations affecting domestic and foreign operations, including tax obligations; changes in generally accepted accounting principles; any changes in business, political and economic conditions due to the threat of future terrorist activity in the U. S. and other parts of the world, and related U. S. military action overseas; growth in costs and expenses; changes in our product, segment and geographic mix; and the impact of acquisitions, divestitures, restructurings, product withdrawals and other unusual items, including our ability to realize the projected benefits of our Adapting to Scale multi-year productivity initiative, including the benefits of the planned broadening of this initiative in 2007 and 2008, and the ability of the Company and Johnson & Johnson to satisfy the conditions to closing the sale of the Company's Consumer Healthcare business, including receiving the required regulatory approvals A further list and description of these risks, uncertainties and other matters can be found in the Company's Annual Report on Form 10-K for the fiscal year ended December 31, 2005, and in its reports on Forms 10-Q and 8-K.   This document includes discussion of certain clinical studies relating to various in-line products and product candidates. These studies typically are part of a larger body of clinical data relating to such products or product candidates, and the discussion in this webcast should be considered in the context of the larger body of data.      (1) "Adjusted income" and "adjusted diluted earnings per share (EPS)" are        defined as reported net income and reported diluted EPS excluding        purchase-accounting adjustments, merger-related costs, discontinued        operations, and certain significant items. As described under        Adjusted Income in the Management's Discussion and Analysis of        Financial Condition and Results of Operations section of Pfizer's        Form 10-Q for the quarterly period ended October 1, 2006, management        uses adjusted income, among other factors, to set performance goals        and to measure the performance of the overall company. We believe        that investors' understanding of our performance in enhanced by        disclosing this measure. The adjusted income and diluted EPS measures        are not, and should not be viewed as, substitutes for U.S. GAAP net        income and diluted EPS. Photo: A free corporate logo to accompany this story is available immediately via Wieck Photo Database to any media with telephoto receiver or electronic darkroom, PC or Macintosh, that can accept overhead transmissions. To retrieve a logo, please call 972-392-0888. SOURCE: Pfizer Inc   CONTACT: Andy McCormick of Pfizer, +1-212-733-5469   Web site: http://www.pfizer.com/

Impact of Vioxx on the pharmaceutical R&D

By Dr. Krishan Maggon, Ph.D., Pharma Biotech R&D Advisor ICC- 20 route de Pre Bois, 1215, Geneva 15, Switzerland maggonk@yahoo.com Volume 4, November 2004. The withdrawal of rofecoxib (Vioxx) by Merck [1-3] has put pressure over the research based pharmaceutical industry, which is driven by unmet medical needs. The current drug approval system, marketing of drugs, directed consumer advertising, high priced new medicines coupled with the end of the blockbuster drug model, low R&D productivity, increasing costs and generic drugs have collectively put the future growth of the big pharma at risk. Merck has been the dominant R&D driven and most admired company during the 1980s and 1990s and had one of the highest market valuations in the industry. During the past two years, it has lost 55% of the market value including the loss of 40% of market value after rofecoxib news [1-3]. Thus, a sale loss of $2.5 billion of rofecoxib resulted in a loss of $27 billion market value in one day and another $20 billion within the next month. Several analysts had downgraded the stock due to late termination of two R&D projects in Phase III last year, rofecoxib withdrawal, federal, states and SEC investigations, product injury and litigations costs and the patent expiry of Zocor in 2006. Drug stocks of research based companies have lost 5-10% of the market value (total loss $50 billion) due the intense media coverage and concerns about the class cardiotoxicity of all Cycooxygenase II inhibitors (coxibs) [4-7]. Every day since withdrawal of rofecoxib, new class action lawsuits are filed in courts against Merck. Wyeth, Pfizer, and Bayer made provisions of $15 billion for previous withdrawals like Phen-fen (Redux), Glitazone (Rezulin) and Cerivastatin (Baycol) respectively. Analysts have provided estimates of up to $20 billion for rofecoxib litigation. Four selective COX II inhibitors are marketed in Europe and two in USA. Celecoxib (Celebrex) and valdecoxib (Bextra) are approved in the USA, while Parecoxib (Dynastat), Etoricoxib (Arcoxia) and Lumiracoxib (Prexige) are marketed in European countries. Celecoxib was the top selling coxib in 2000 and 2001 with sales of $2 billion and $3 billion, respectively but lost market leadership to rofecoxib in 2002 and 2003 due to better gastrointestinal (GI) tolerance. In the first half of 2004, global sales of COX II inhibitors were: celecoxib $1.5 billion, rofecoxib $1.3 billion, valdecoxib $545 million and etoricoxib $92 million. Celecoxib is expected to reach annual sales of $3 billion in 2004. Worldwide 80-100 million patients have used celecoxib and rofecoxib and 40 million in USA. The history of modern drug regulations is closely linked to the incidence of drug induced injury, organ failure and deaths (Table 1). Each tragedy linked to marketed drugs resulted in increased regulations and additional testing to prevent future episodes with new drugs of the same class (Table 2). The Elixir of Sulfanilamide tragedy resulted in the Food, Drug and Cosmetic Act of 1938. The Thalidomide tragedy in early 1960 resulted in requirements for safety and efficacy testing for drugs in animals and humans. Safety testing includes testing new drugs for adverse effects; for example, can a new chemical entity (NCE) cause birth defects, cancer, organ failure, organ toxicity or some other problem. Willman of The Los Angeles Times was honored with a Pulitzer Prize in 2001 for his investigative reporting of FDA fast track approval and seven deadly drugs in 2000 including Rezulin, Fen-Phen and Duract (bromfenac) [8]. All drug withdrawals are followed by regulatory review of similar drugs to rule out a class effect, additional safety data for marketed drugs and additional requirements for drugs in development. The withdrawal of benoxaprofen resulted in a ten fold increase in number of patients (from 200-400 patient year exposure to 2500-5000 patient year exposure to the study drug) required for newer NSAID (Non Steroidal Anti Inflammatory Drugs) and trials in elderly, hepatic and renal impairment and drug interactions. International guidelines require that for long-term treatment of non-life-threatening conditions, 1500 patients should be treated with the drug: for safety-300-600 treated for at least 6 months, and for efficacy at least 100 for 12 months. FDA has routinely required 200 patients treated for 1 year. Astra Zeneca total patient exposure in clinical trials submitted for approval for rosuvastatin (12,500) was considerably greater than the 2,000-3,000 patients submitted for most of the other marketed statins. Since the withdrawal of troglitazone (Rezulin), no other Peroxisome Proliferator Activator Receptor (PPAR) agonist has been approved because of the concerns about the class carcinogenicity, hepatotoxicity and cardiotoxicity. The published and available clinical data indicates an increased cardiac risk to patients linked to the long term use of rofecoxib [9-11]. Cardiovascular (CV) events linked to Cox-II inhibitors, include heart attack, stroke, high blood pressure, fluid retention and heart failure. After rofecoxib, a winning strategy for a safe and effective anti-inflammatory and analgesic COX-II agent is to reduce GI toxicity and not have any cardiovascular, renal, hepatic, neurological or any other toxicity. Toxicology studies in monkeys, in addition to rodents and dogs may help identifying CV risks early in drug development. Clinical trials to generate data for approval and show reduced GI toxicity and CV safety will require 25,000-30,000 patients with several thousands treated for 2-3 years. This is confirmed by recent FDA stance for additional long term safety data for the approval of etoricoxib and lumiracoxib. This has been the requirement for approvals of some new vaccines and drugs for common cold. The industrial R&D should move away from the twin focused NSAID induced GI toxicity and total COX II inhibition. The optimum COX II inhibition may provide cardiac, hepatic, renal, immunological and CNS safety [12, 13]. The total R&D costs for such a drug will be $1.5 billion over 12-15 years. If successful, the rewards are a blockbuster analgesic drug with potential annual sales of $5 billion. The available data indicates a differentiation of available COX-II inhibitors with respect to GI and CV effects [14]. Etoricoxib (Arcoxia) show reduced GI toxicity without increased CV risk but long term data is not available. Valdecoxib (Bextra), Parecoxib (Dynastat) and Lumiracoxib (Prexige) show reduced GI toxicity with increased CV risk. Rofecoxib showed reduced GI toxicity with increased CV risk. Celecoxib (Celebrex) has a similar GI toxicity as popular NSAIDS but may have a potential cardioprotective effect according to Pfizer but increased CV risk according to its critics.

References Merck Background Information Vioxx. http://www.merck.com/newsroom/vioxx_withdrawal/ Henry D. (2004) Market Lessons From Merck's Decline. Business Week. October 18, 2004. Maggon K. Shock and pain after rofecoxib. Express pharma Pulse 21 October 2004. http://www.expresspharmapulse.com/20041021/edit02.shtml FitzGerald, GA. Coxibs and Cardiovascular Disease. N Engl J Med 2004; 351:1709-1711. Topol, EJ. Failing the Public Health -Rofecoxib, Merck, and the FDA N Engl J Med 2004; 351:1707-1709. Dieppe P. et al. Balancing benefits and harms: the example of non-steroidal anti-inflammatory drugs. BMJ 2004; 329: 31-4. Howard, PA. and Delafontaine, P. Non steroidal anti-inflammatory drugs and cardiovascular risk. J. Am Coll. Cardiol. 2004; 43: 519.525. Willman. D. The new FDA; How a New Policy Led to Seven Deadly Drugs; The Los Angeles Times ; Dec 20, 2000; pg. A.1 http://www.pulitzer.org/year/2001/investigative-reporting/works/rezulin.html Bombardier C, et al. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. N Engl J Med 2000; 343:1520-8. Ott, E. et al. Efficacy and safety of the cyclooxygenase 2 inhibitors parecoxib and valdecoxib in patients undergoing coronary artery bypass surgery. J. Thorac. Cardiovasc. Surg. 2003; 125: 1481-1492, Farkouh ME, et al. Comparison of lumiracoxib with naproxen and ibuprofen in the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET), cardiovascular outcomes: randomised controlled trial. Lancet 2004; 364: 675-684. Maggon K. The future of the research based pharmaceutical industry. Editorial Express Pharma Pulse. January 29, 2004. http://www.expresspharmapulse.com/20040129/oped01.shtml Maggon K. Cardiotoxicity of Selective COX II Inhibitors. Express Pharma Pulse 25 November 2004.In Press. American College of Rheumatology Meeting Hotline 2004. Cardiovascular Complications Related to COX-2 Inhibitors. http://www.rheumatology.org/publications/hotline/0904chfvioxx.asp Dr. K. Maggon, Ph.D. is International industry consultant based in Geneva, Switzerland with a successful track record in new drug development, project management, clinical trials, business development, licensing, market introduction/support, contract and R&D evaluation, external research management and training. New drug development experience in Cardiovascular, CNS, Biotechnology Products, Imaging agents, Immune disorders, Anti Cancer and Infectious Diseases. Established leadership skills and ability to get results. Extensive contacts with key scientific, medical and technical academic and industrial leaders worldwide. 90 publications. Contributed to the development of over 50 products from Phase 1-IV. Added significant value to drug candidates. Annual sales of marketed products were over $4.5 billion in the year 2003. Dr Krishan Maggon, an alumnus of Delhi University, did post doctoral research at the University of Geneva. With more than 20 years experience in new drug R&D at reputed pharma and start up companies, Dr Maggon was involved in the early development of Losartan (2003 sales $2.5 billion) and has authored over 90 research publications in various international journals. *Please reference or credit any material, article or figure cited from http://www.medicineandbiotech.com as: Copyright 2004. MedicineandBiotech.com, http://www.medicineandbiotech.com/ Disclaimer: Please re-distribute MedicineandBiotech.com e-magazine. MedicineandBiotech.com does not assume, and hereby disclaim, any liability for any loss or damage caused by errors or omissions in any material published at the web-site http://www.medicineandbiotech.com, whether such errors or omissions resulted from negligence, misstatements or other oversights.

Combination Therapy to Fight Cancers We are in the era of designer drugs. However, cancers result from complex genetic alterations with multiple genes being cancer culprits. Companies like Bayer, GlaxoSmithKline, Pfizer and Wyeth are following the trend of developing combination therapy regimens where targeting multiple targets simultaneously may prove to be a more effective therapeutic strategy. Majority of the biotech companies and big Pharma have at least one favorite designer drug for treatment of a particular cancer. Most researchers and drug companies had hoped that one super drug could destroy that one critical cancer-causing protein, resulting in remission of cancer, followed by a long-term cure. The problem with this scenario at a molecular level, is that every cancer or tumor has multiple defective genes, which are driving the cancers or tumors towards uncontrolled cellular proliferation and persistent genetic instabilities. Therefore, targeting one particular gene, especially in the case of breast, colon, lung, and prostate cancers may not be the ultimate cure. Currently, Bayer, Pfizer, Genentech and other firms are developing combination therapy, with the ability to inactivate multiple defective cancer causing proteins with diverse molecular structures. Another strategy is to combine two or more drugs targeted at one particular target. This strategy can be effective when targeting multiple kinases, which are well-known cancer promoting proteins and may have similar structures. Combination therapy has shown some positive impact in treatment of certain kidney, breast, and lung cancers. The table here summarizes the current stage of combination therapy being tested by various companies. Dr. Neerja Sethi, Ph.D.