PHARMACEUTICALS

 


Sanofi-aventis’ SoloSTAR® Disposable Insulin Injection Pen for Diabetes Patients Receives the Prestigious GOOD DESIGN Award

February 2008. The Chicago Athenaeum Museum of Architecture and Design has awarded a 2007 GOOD DESIGN™ Award for the new SoloSTAR® disposable insulin injection pen for people with type 1 and type 2 diabetes.

“LANTUS®  SoloSTAR® and APIDRA® SoloSTAR®, the results of over four years of intensive development, have been designed in dialogue with patients, nurses and doctors and meet the high standards of the industry,” said Paul Jansen, Global Head Medical Devices, Sanofi-aventis.

For some people with diabetes, self-injection can be a barrier to acceptance of insulin therapy. “SoloSTAR® is a marriage of sleek, handsome design styling with easy, but advanced sophisticated technology for dispensing insulin to people with diabetes,” says Christian K. Narkiewicz-Laine, President Chicago Athenaeum Museum of Architecture and Design.

“SoloSTAR® represents a design for social good and for humanitarian concerns”.

When choosing a specific insulin pen for an individual patient, clinicians consider the patient's insulin regimen, lifestyle, and other factors that may affect the ability to use a particular device, such as manual dexterity and visual acuity. Therefore certain characteristics of a given insulin pen may make it preferable for patients. The outstanding design of SoloSTAR® using breakthrough technology contributes to making this patients’ and clinicians’ choice easier.

SoloSTAR® provides a delivery option that may be more acceptable and more convenient to use in comparison with other delivery systems, thus may promote patient compliance, which could help achieve and maintain glycemic control.

A recent survey of LANTUS® SoloSTAR® use in everyday clinical practice, involving more than 2000 people with diabetes (16% with manual dexterity problems and 15% with poor eyesight not corrected by glasses) showed that more than 95% of participants declared to be “satisfied” or “very satisfied” with using SoloSTAR® to inject insulin, irrespective of diabetes type or previous device experience.

Healthcare professionals involved in teaching the people in this survey how to use LANTUS® SoloSTAR® found SoloSTAR® to be easy learn and easy to use for people with diabetes. SoloSTAR® also operates with a lower injection force and a recent study found that SoloSTAR® required 31% less injection force than the Novo Nordisk FlexPen® and 54% less force than the Eli Lilly Humulin/Humalog pen.

“Insulin injection with SoloSTAR® brings flexibility, satisfaction for the patients, and an opportunity for earlier initiation of insulin therapy which may contribute to better long term glycaemic control”, Denis Raccah, Professor of Endocrinology, University Hospital Sainte Marguerite, France, added.

About SoloSTAR®

SoloSTAR® is a new, easy-to-use disposable pen for administration of LANTUS® and APIDRA®. SoloSTAR®, allows to administer doses from 1 up to 80 units, in one unit increments, in one injection. SoloSTAR offers a 25% greater maximum capacity than other insulin pens. Consequently, the administration until 80 units of insulin can be done with only one injection. SoloSTAR uses a simple, intuitive design with easy-to-read display featured and requires only a few steps to use it properly. SoloSTAR® is small, discreet and eliminates the need for the patient to change insulin cartridges. Easy-to-use and easy-to-inject, SoloSTAR® reduces the injection force by 30% or more in comparison to other most broadly available pens in its class.

Lantus® SoloSTAR® and APIDRA® SoloSTAR® were approved by the EMEA in September 2006; LANTUS® SoloSTAR® was approved by the FDA in April 2007. LANTUS® SoloSTAR® and APIDRA® SoloSTAR® are launched in France, UK, Italy, Spain, Germany, Netherlands, Slovakia, Slovenia, Sweden, Norway, Austria, Denmark, Estonia, Finland, Greece, Hungary, Ireland, Latvia, Australia, Lithuania, Lebanon, and South Africa. LANTUS® SoloSTAR® is launched in the US, Canada and Switzerland. The preparation for launches in other countries is planned during 2008.

The elegant exterior design of Lantus® and Apidra® SoloSTAR® and its ease of use due to advanced technology is the result of the collaboration with DCA Design International Ltd. in Great Britain DCA Company.

About Sanofi-aventis’ pen portfolio

Sanofi-aventis having 85 years of innovation in the diabetes is committed to offering people with diabetes an integrated system of insulin products and delivery devices. In addition to the SoloSTAR®, the pen portfolio available for LANTUS® and APIDRA® includes the OptiSet® disposable pen, the OptiClik® and OptiPen® Pro reusable pens, and the Autopen® 24 from Owen Mumford.

About LANTUS® (insulin glargine [rDNA origin])

LANTUS® is indicated for once-daily subcutaneous administration in the treatment of adult patients with type 2 diabetes mellitus who require basal (long-acting) insulin for the control of hyperglycemia and for adult and pediatric patients (6 years of age and older) with type 1 diabetes mellitus. LANTUS® demonstrates a consistent slow, prolonged absorption and a relatively constant concentration/time profile over 24 hours.

About APIDRA® (insulin glulisine [rDNA origin])

APIDRA® is a rapid-acting insulin analog with a unique zinc-free molecular structure that maintains a rapid onset and a short duration of action, indicated for adult patients with type 1 and type 2 diabetes. APIDRA® offers patients mealtime dosing flexibility—it can be taken 15 minutes before or within 20 minutes after starting a meal. APIDRA® is also flexible for use in patients with a variety of body types, from lean to obese.

About Diabetes

Diabetes is a chronic, evaluative widespread disease in which the body reduces or does not produce or properly use insulin – the hormone needed to convert glucose (sugar) into energy. More than 240 million people worldwide are living with the disease. It is estimated that near 250 million people worldwide have diabetes, the number is expected to reach some 380 million within 20 years.

It is estimated more than 20 million Americans have diabetes, including an estimated 6.2 million who remain undiagnosed. At the same time, approximately half of those diagnosed are not achieving the general blood sugar control standard of A1C <7% recommended by the American Diabetes Association and the European Association for the Study of Diabetes (ADA/EASD). The A1C test reflects average blood glucose levels over a two- to three-month period.

Without proper insulin production and action, glucose remains in the blood, leading to chronic hyperglycaemia (raised blood sugar). This can result in short and long-term complications, many of which, if not prevented and left untreated, can be fatal. All have the potential to reduce the quality of life of people with diabetes and their families.

The most common long-term complications are:

- Diabetic nephropathy (kidney disease), which may result in total kidney failure and in the need for dialysis or kidney transplant.

- Diabetic eye disease (retinopathy and macular oedema), damage to the retina of the eye

which can lead to vision loss.

- Diabetic neuropathy (nerve disease), which can ultimately lead to ulceration and amputation of the feet and lower limbs.

- Cardiovascular disease, which affects the heart and blood vessels and may cause fatal

- complications such as coronary heart disease (leading to a heart attack) and stroke.

Diabetes is the fourth leading cause of death by disease globally. Every year, 3.8 million people die from diabetes-related causes.

About GOOD DESIGN

The Museum’s historic GOOD DESIGN program was founded in Chicago in 1950 by Edgar J.Kaufmann, Jr. with the participation of some of America’s most important designers. Every year the jury meets in New York and select products and graphics worthy of the GOOD DESIGN Award for design distinction. GOOD DESIGN remains the oldest and most important Awards program worldwide.

About Sanofi-aventis

Sanofi-aventis, a leading global pharmaceutical company, discovers, develops and distributes therapeutic solutions to improve the lives of everyone.

References:

For easy to inject

Owens DR. Comparison of insulin pen devices reveals lower injection force of Solostar® compared with novo Flexpen® and lilly® disposable pen; Diabetes Technology Meeting 25–17 October 2007, San Francisco, CA, USA. Journal of Diabetes Science and Technology, March 2008; Abstract OWEN70184; In press.

Clarke A, Spollett G. Dose accuracy and injection force dynamics of a novel disposable insulin pen. Expert Opin. Drug Deliv. (2007) 4(2):165-174.

For easy to use and patient’s satisfaction

Carter J et al. Usability, participant acceptance and safety of SoloStar in an observational survey in everyday clinical practice; Diabetes Technology Meeting 25–17 October 2007, San Francisco, CA, USA. Journal of Diabetes Science and Technology, March 2008; Abstract CART70119; In press.

Source: Sanofi-Aventis Press Release

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Affymetrix Launches World's Most Comprehensive Solution for Clinical Drug Metabolism Studies for Pharmaceutical Research

--Drug Metabolizing Enzymes and Transporters (DMET) Early Access Solution Enables Pharmaceutical Researchers to Assess all Clinically Relevant ADME Markers in a Single Assay--

SANTA CLARA, Calif-Jan. 24, 2008--Affymetrix Inc. announced the availability of its Drug Metabolizing Enzymes and Transporters (DMET) Early Access solution, currently the world's most comprehensive method for assaying the genetics of drug metabolism. The DMET offering profiles more than 1,069 drug metabolism biomarkers, including 172 "core" genetic markers. Data is automatically interpreted into a common format that can be integrated into clinical trial workflows. The information enables researchers to make more informed drug-development decisions, which in turn significantly streamlines the drug-development process and, therefore, time to market.

The DMET solution is available as a service through Affymetrix' South San Francisco Services Laboratory and Cogenics, a subsidiary of Clinical Data. Both providers have been accepting samples since the fourth quarter of 2007, following the successful completion of a six-week training and certification program to ensure that data is complete, accurate and reproducible. Cogenics is offering DMET as a Good Laboratory Practice (GLP)-compliant service from its North Carolina facility, while Affymetrix' South San Francisco facility is running the service strictly for non-GLP research studies. Additional worldwide service providers will be certified and announced in the near future. Affymetrix and Clinical Data announced a joint marketing agreement today in a separate press release.

Pharmaceutical customers are using the DMET solution to better understand pharmacokinetics, the study of the bodily absorption, distribution, metabolism and excretion (ADME) of drugs. DMET is the only product available with comprehensive coverage of all ADME drug metabolism biomarkers, including common and rare variations, insertions, deletions, copy number, triallelic SNPs and pseudogenes. For the first time, scientists are able to assess all clinically relevant ADME markers in a single assay, unlike previously used single-plex approaches.

"Being able to measure a variety of 'core' genetic markers is critical to delivering accurate clinical assays, something the Affymetrix technology is allowing us to achieve. Accurate clinical assays have the ability to deliver improved patient outcomes because the medicines we develop become more directly targeted to the patient's specific needs," said Richard Deane Hockett, senior clinical research physician, group leader for genomic medicine, Department of Diagnostic and Experimental Medicine at Eli Lilly & Co. "We are implementing this technology across the research portfolio in all phases of clinical trials at Lilly."

Regulatory authorities have indicated a renewed interest in surveying drug metabolism biomarkers to ensure safer dosing, which in turn reduces the possibility of adverse events and improves patient safety. Just three months ago, the U.S. Food and Drug Administration (FDA) made history by updating the label on the anticoagulant drug, Warfarin, to include information on CYP2C9 and VKCORC1.

According to a commentary in Clinical Pharmacology and Therapeutics co-authored by the FDA(1), "Pharmacogenomic data can facilitate our understanding of the sources of variability in drug response and can potentially lead to improved safety and efficacy of drug therapy for individual patients. Through various initiatives, the FDA is encouraging drug developers to apply the rapidly evolving pharmacogenomic tools and integrate these data into the evaluation of patient variability."

Michael Caldwell, M.D., Ph.D., director of the Wound Healing Program at Marshfield Clinic, has been using the DMET solution to research the genetics behind an individual's drug response to Warfarin, a drug that if prescribed at the wrong dose can have serious adverse events. "The DMET panel has allowed us to better delineate the stable therapeutic dose of Warfarin for our patients at the initiation of therapy, where risk of complications from the drug are at their highest," said Dr. Caldwell. "Thus our hope is that these studies will enable us to reduce the overall complications of Warfarin therapy by a better prediction of stable therapeutic dose."

The DMET solution features easy-to-use patient consent tracking and data translation software to identify functional variants across the panel and to convert genotyping results into standardized star nomenclature, a convention commonly used in the genetic analyses of clinical trials. The automated analysis takes only a few minutes to complete and provides pharmaceutical researchers performing clinical trials with familiar data that can be easily integrated into existing workflows. Previously, this analysis was a manual and time-consuming task as scientists were required to scour literature for relevant answers.

"DMET Early Access is the result of an ongoing Affymetrix commitment to develop assays that are targeted at clinical drug development," said Maneesh Jain, senior director of marketing at Affymetrix. "We've been fortunate to work with leading pharmaceutical partners and key medical centers to design and develop an assay that's comprehensive for ADME biomarkers and directly provides information with clinical utility."

About Affymetrix

Affymetrix GeneChip(R) microarray technology is the industry-standard tool for analyzing complex genetic information. After inventing microarray technology in the late 1980s, Affymetrix scientists have been dedicated to developing innovative products that provide researchers with a more complete view of the genome. These products continue to accelerate genetic research and enable scientists to develop diagnostics and tailor treatments for individual patients by identifying and measuring the genetic information associated with complex diseases.

Today, Affymetrix technology is used by the world's top pharmaceutical, diagnostic and biotechnology companies, as well as leading academic, government and not-for-profit research institutes. More than 1,600 systems have been shipped around the world and more than 10,500 peer-reviewed papers have been published using the technology.

Affymetrix is headquartered in Santa Clara, Calif., and has manufacturing facilities in Sacramento, Calif., and Singapore. The company has about 1,100 employees worldwide and maintains sales and distribution operations across Europe and Asia. For more information about Affymetrix, please visit: www.affymetrix.com.

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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: 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

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: [email protected]

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).

         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

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).

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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

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* 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/

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

[email protected]

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 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. 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.

  • Merck Background Information Vioxx. http://www.merck.com/newsroom/vioxx_withdrawal/
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    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/

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