New Data Shows Rimonabant Benefited Patients With Type 2 Diabetes By Improving Blood Sugar Control And Reducing Weight

Sanofi-aventis announced today that new data on rimonabant, its first-in-class cannabinoid type 1 (CB1) receptor blocker, showed that patients with type 2 diabetes not currently treated with anti-diabetic medications experienced significant improvements in blood sugar control and weight as well as other risk factors such as HDL-cholesterol (good cholesterol) and triglycerides when compared to placebo. The study, called SERENADE, was presented today at the International Diabetes Federation (IDF) World Diabetes Congress in Cape Town, South Africa. SERENADE is the second study demonstrating that rimonabant significantly improved blood sugar levels in people with type 2 diabetes.

In the SERENADE study, treatment-naive type 2 diabetes patients receiving rimonabant 20mg per day for a duration of six months significantly lowered their HbA1c levels by 0.8% from a baseline value of 7.9 as compared to a reduction of 0.3% in the placebo group (p=0.002). In addition, patients with an HbA1c level greater than or equal to 8.5% at baseline, significantly reduced their HbA1c by 1.9% with rimonabant as compared to 0.7% with placebo (p
“The management of type 2 diabetes should not only focus on controlling blood sugar levels but also improve other risk factors such as weight, good and bad cholesterol, triglycerides and blood pressure,” said Julio Rosenstock, M.D., Director of the Dallas Diabetes and Endocrine Center at Medical City and also Clinical Professor of Medicine at the University of Texas Southwestern Medical School, Dallas, Texas who was an investigator in the SERENADE trial. “This study suggests that rimonabant can achieve improvement in blood glucose with the added benefit of significant weight loss and improvement in other risk factors.”

Today, more than 194 million adults or 5% of adults worldwide have been diagnosed with diabetes, with type 2 diabetes constituting 85-95% of all diabetes in developed countries.(ii) Approximately 90 percent of type 2 diabetes is attributed to people being overweight or obese.(iii) Diabetes and obesity are often associated with other risk factors for cardiovascular disease including high blood pressure and unhealthy cholesterol. Worldwide, diabetes is among the leading causes of blindness, renal failure and lower limb amputation, as well as death through its effects on cardiovascular disease (70-80 percent of people with diabetes die of cardiovascular disease).(ii)

Accompanying the improvements in HbA1c and weight seen in the rimonabant arm of the SERENADE trial were improvements in multiple cardiometabolic risk factors. Patients in the rimonabant arm decreased their waist circumference (a measure of abdominal obesity) by 6.1 cm (2.34 in) compared to a 2.4 cm (0.93 in) decrease for patients on placebo (p
Approximately 57% of the improvements in HbA1c (p
The overactivity of the Endocannabinoid System (ECS) in the fat tissue and muscle is found to promote fat accumulation and decrease glucose uptake, which can lead to an increased risk of developing insulin resistance and impaired glucose tolerance. By selectively blocking CB1 receptors of the ECS, which according to animal and human studies can be found in the brain, fat tissue, gastrointestinal tract, pancreas, liver and muscle, rimonabant results in a decrease in food intake, a loss of body weight, and direct improvements in blood sugars (HbA1c), HDL-cholesterol and triglycerides.

“Some current medications for type 2 diabetes are often associated with weight gain,” said Julio Rosenstock. “The fact that blood sugar levels were reduced along with weight loss and improvements in HDL-cholesterol (“good” cholesterol) and triglycerides may further support the novel mechanism of action of rimonabant, which is different from the mode of action of current oral anti-diabetic medications.”

The most common side effects with placebo and rimonabant 20mg reported in the SERENADE trial were dizziness (2.1% vs. 10.9%), nausea (3.6% vs. 8.7%), nasopharyngitis (7.9% vs. 7.2%), upper respiratory tract infection (2.7 % vs. 7.2%), anxiety (3.6% vs. 5.8%), depressed mood (0.7% vs. 5.8%), and headache (6.4% vs. 3.6%). The rate of serious adverse events was 3.6% for patients in the placebo arm versus 6.5% for patients in the rimonabant 20 mg.

Overall, discontinuation rates due to adverse events in the trial were 2.1% in placebo-treated patients versus 9.4% for patients on rimonabant 20mg. The most common adverse events leading to discontinuation for the placebo and rimonabant 20mg patients, respectively, were nausea (0% vs. 2.2%), depressed mood disorder (0% vs. 2.2%) and paraesthesia (0% vs. 2.2%).

About SERENADE

SERENADE (Study Evaluating Rimonabant Efficacy in Drug-NAive DiabEtic Patients) was a multi-center, randomized, double-blind, placebo-controlled, parallel-group study comparing rimonabant 20mg once daily to placebo in improving blood sugar control (as indicated by HbA1c) in treatment-naive type 2 diabetic patients not adequately controlled by diet alone for a period of six months.

The study was conducted on 278 patients at 56 study centers in the United States, Germany, Argentina, Chile, Hungary, Poland and the Netherlands. The primary endpoint of the trial was change from baseline of HbA1c levels. Secondary endpoints included weight and waist circumference, a key marker of intra-abdominal adiposity, fasting plasma glucose, lipid parameters and arterial blood pressure.

To be included in the trial patients had to have a diagnosis of type 2 diabetes for at least two months but less than three years, HbA1c levels greater than 7% and less than 10%, and could not have been treated previously with an anti-diabetic medication within six months prior to screening.

SERENADE is part of an extensive worldwide Phase IIIb clinical trial program involving over 22,000 patients in eight studies, which will investigate the role of rimonabant in the treatment of type 2 diabetes and cardiovascular disease.

About Rimonabant

In Europe, rimonabant, known as ACOMPLIA(R) is approved as an adjunct to diet and exercise for the treatment of obese patients (BMI>or equal to 30kg/m2), or overweight patients (BMI>27kg/m2) with associated risk factors, such as type 2 diabetes or dyslipidemia. Rimonabant is currently commercialized in the United Kingdom, Germany, Denmark, Sweden, Finland, Norway, Ireland, Argentina and Austria.

At the end of October 2006, sanofi-aventis submitted a complete response to the U.S. Food and Drug Administration (FDA) approvable letter received in February 2006.

About sanofi-aventis Sanofi-aventis is the world’s third largest pharmaceutical company, ranking number one in Europe. Backed by a world-class R&D organization, sanofi- aventis is developing leading positions in seven major therapeutic areas: cardiovascular, thrombosis, oncology, metabolic diseases, central nervous system, internal medicine, and vaccines. Sanofi-aventis is listed in Paris (EURONEXT: SAN) and in New York (NYSE: SNY).

Forward Looking Statements

This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995. Forward-looking statements are statements that are not historical facts. These statements include financial projections and estimates and their underlying assumptions, statements regarding plans, objectives and expectations with respect to future events, operations, products and services, and statements regarding future performance. Forward-looking statements are generally identified by the words “expects,” “anticipates,” “believes,” “intends,” “estimates,” “plans” and similar expressions. Although sanofi-aventis’ management believes that the expectations reflected in such forward-looking statements are reasonable, investors are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of sanofi-aventis, that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include those discussed or identified in the public filings with the SEC and the AMF made by sanofi-aventis, including those listed under “Risk Factors” and “Cautionary Statement Regarding Forward- Looking Statements” in sanofi-aventis’ annual report on Form 20-F for the year ended December 31, 2005. Other than as required by applicable law, sanofi- aventis does not undertake any obligation to update or revise any forward- looking information or statements.

For more information, log onto http://www.sanofi-aventis.com.

References:

i American Diabetes Association. Standards of Medical Care in Diabetes 2006. Diabetes Care 2006;29:S4-42.

ii The International Diabetes Federation Diabetes Atlas. Available at: http://www.idf.org/home/index.cfm?unode=3B96906B-C026-2FD3-87B73F80BC22682A. Last Accessed November 15th, 2006.

iii World Health Organization, http://www.diabetes.org/diabetes-heart-disease-stroke.jsp. Last accessed 11/17/08/p2/Line 63-64.

sanofi-aventis
http://www.sanofi-aventis.us

Ragweed pollen main cause of hay fever (seasonal allergy symptoms)

Ragweed is a prolific pollen producer and the number one cause of seasonal allergy symptoms according to the American College of Asthma, Allergy and Immunology (ACAAI).

“A single ragweed plant can produce up to 1 billion pollen grains, and each grain can travel more than 100 miles from its source,” said Richard W. Weber, M.D., National Jewish Medical and Research Center, Denver, and chair of the ACAAI Aerobiology Committee that specializes in pollen and mold allergens.

“Throughout much of the country, people with pollen allergies already have suffered through high pollen counts from spring pollinating plants. Once the dry weather conditions of late summer and autumn take hold, ragweed’s profuse pollen is released into the air, accounting for 75 percent to 90 percent of all pollen found from August through October in some regions,” Dr. Weber said.

“Peak ragweed pollen counts start first in the North, hitting around Labor Day. Southern states experience peak conditions in late September or mid-October. But if people are prepared and know what to do, they can get through it with a minimum of discomfort,” he said.

Allergists – doctors who specialize in treatment of allergic diseases including asthma – want people to know that increasing amounts of ragweed pollen in the air can also trigger life-threatening asthma symptoms such as wheezing and difficulty breathing.

Children with allergies are particularly at risk of developing asthma during peak pollen seasons. A three-year study of children with seasonal allergies found that 1 in 5 experienced asthma symptoms during pollen season, even though they had no previously reported history of asthma.

“Noted aerobiologists agree that the time of day when pollen is at peak levels will vary from plant to plant,” said allergist-immunologist Warren V. Filley, M.D., Oklahoma City, Okla.

“Ragweed pollen is released onto the plant leaves at daybreak, then depending upon the dew and wind conditions, it usually is at it highest airborne level between 10:00 a.m. and noon, but this is variable.”

The ACAAI recommends the following actions to minimize ragweed pollen allergy symptoms:

— Begin allergy medications one or two weeks ahead of the ragweed season. The best medications work by inhibiting the immune system’s release of chemicals that can cause allergic reactions and, if taken prior to exposure to pollens, can help stabilize your immune system before you experience symptoms. Talk to your family doctor or an allergist about the best medications for you.

— If medications don’t provide sufficient relief or if you experience medication side effects, talk to an allergist about allergy shots, or immunotherapy. Allergy shots can provide long-term relief by stimulating the immune system to fight allergies safely, effectively and naturally. Immunity does not occur immediately, but you can expect some relief quickly. You also may be a candidate for “rush” immunotherapy, a type of vaccination process that speeds up the development of immunity.

— When gardening or mowing the lawn, wear a particle mask.

— Take your allergy medications before going outdoors.

— Wear sunglasses to keep pollen from getting into your eyes.

— After being outdoors, bathe and wash your hair, change your clothes and use a nasal salt water rinse to remove pollens.

— Check out your local television or newspaper weather reports for pollen counts and forecasts. When counts are high, avoid outdoor activities.

More information on allergic rhinitis, allergic asthma and immunotherapy is available by calling the ACAAI toll free number at (800) 842-7777 or visiting its Web site at http://www.acaai.org.

The ACAAI is a professional medical organization comprising nearly 5,000 qualified allergists-immunologists and related health care professionals. The College is dedicated to the clinical practice of allergy, asthma and immunology through education and research to promote the highest quality of patient care.

American College of Allergy, Asthma and Immunology (ACAAI)
85 W. Algonquin Rd., Ste 550
Arlington Heights, IL 60005
United States
http://www.acaai.org

Spectrum Pharmaceuticals Announces Initiation Of Phase 2 Trial Evaluating Satraplatin In Combination With Tarceva In Patients With Lung Cancer

Spectrum Pharmaceuticals, Inc. (Nasdaq: SPPI) announced today that its partner, GPC Biotech, has initiated a Phase 2 randomized trial evaluating satraplatin in combination with Tarceva(R) (erlotinib) as a first-line therapy in patients with inoperable, advanced non-small cell lung cancer (NSCLC) who are 70 years of age and older. A Phase 3 registration trial exploring satraplatin in combination with prednisone as a second-line chemotherapy treatment for patients with hormone-refractory prostate cancer has completed patient enrollment. Additional clinical studies are being explored to explore the potential of satraplatin as a single agent or in combination with different drugs and other treatment modalities in a variety of tumor types.

The Phase 2 study in advanced NSCLC is a randomized trial that is expected to involve more than 20 centers in the U.S. and Europe and enroll approximately 120 patients. The primary objective of this study is to evaluate progression-free survival. The study will also examine overall survival, response rates and safety. Patients in the Phase 2 trial will be randomized to receive satraplatin plus Tarceva or Tarceva alone. A sequential dosing regimen will be used in the satraplatin arm. The treatment cycle for both arms is 28 days. Patients will be stratified according to smoking history and gender.

“We are pleased that our partner is committed to rapidly advancing satraplatin through clinical development in multiple indications,” stated Rajesh Shrotriya, M.D., president and chief executive officer of Spectrum. “Our partnership for the development of satraplatin is consistent with our risk-reduced drug development strategy, and it provides us with a potential source of non-dilutive funding with which we will advance our proprietary oncology pipeline. If successful, we expect to begin receiving milestone and royalty payments for satraplatin as early as next year, starting with the acceptance by the FDA of the NDA submission of the drug for hormone-refractory prostate cancer. The rolling NDA filing remains on track, and is expected to be completed by end of the year”

About Lung Cancer

Lung cancer is the leading cause of cancer death in the U.S., with an estimated 162,000 deaths expected from the disease in 2006. Over 170,000 new cases are expected to be diagnosed in 2006. The five-year survival rate for lung cancer in the U.S. is only 15 percent. Recent statistics for Europe estimated over 375,000 cases annually of lung cancer and over 345,000 deaths from the disease. NSCLC accounts for over 80% of all lung cancer cases, and over 50% of patients present with inoperable disease.

Standard first-line chemotherapy for patients with advanced NSCLC typically involves a combination regimen, frequently with a platinum-based therapy. For elderly patients or patients with a poor performance status, a single-agent chemotherapy may be recommended due to concerns about these patients’ ability to tolerate a combination regimen. Thus, there is a need for well-tolerated, effective combination treatments.

About Satraplatin

Satraplatin, an investigational drug, is a member of the platinum family of compounds. Over the past two decades, platinum-based drugs have become a critical part of modern chemotherapy treatments and are used to treat a wide variety of cancers. Unlike the platinum drugs currently on the market, all of which require intravenous administration, satraplatin is an orally bioavailable compound and is given as capsules that patients can take at home.

Spectrum out-licensed satraplatin to GPC Biotech AG in 2002, and GPC Biotech fully funds all development expenses. In December 2005, the accrual to the Phase 3 registrational trial was completed and the rolling submission of a New Drug Application (NDA) for satraplatin with the U.S. Food and Drug Administration (FDA) was initiated. Also in December 2005, GPC Biotech signed a co-development and license agreement with Pharmion GmbH, a wholly owned subsidiary of Pharmion Corporation, under which Pharmion was granted exclusive commercialization rights to satraplatin for Europe and certain other territories outside the U.S.

Satraplatin has been studied in clinical trials involving a range of tumors, and Phase 2 trials have been completed in hormone-refractory prostate cancer, ovarian cancer and small cell lung cancer. Other trials evaluating the effects of satraplatin in combination with radiation therapy, in combination with other cancer therapies and in various other cancers are underway or planned.

About Spectrum

Spectrum Pharmaceuticals is opportunistically acquiring and advancing a diversified portfolio of oncology drug candidates that meet critical health challenges for which there are few other treatment options. Spectrum’s expertise lies in identifying undervalued drugs with demonstrated safety and efficacy, and adding value through further clinical development and selection of the most viable and low-risk methods of commercialization. The company’s pipeline includes promising early and late-stage drug candidates with unique formulations and mechanisms of action that address the needs of seriously ill patients, such as at-home chemotherapy and new treatment regimens for refractory disease. For more information, please visit our website at http://www.spectrumpharm.com.

Forward-Looking Statement

This press release may contain forward-looking statements regarding future events and the future performance of Spectrum Pharmaceuticals that involve risks and uncertainties that could cause actual results to differ materially. These statements include but are not limited to statements that relate to our business and its future, Spectrum’s ability to identify, acquire and develop its portfolio of drug candidates, the Company’s promising pipeline, that Spectrum will receive royalties from sales of satraplatin, the expected number of centers and patients involved in the Phase 2 study, that satraplatin provides us with a potential source of non-dilutive funding with which we will advance our proprietary oncology pipeline, that we will begin receiving milestone and royalty payments from GPC Biotech for satraplatin as early as next year, the acceptance by the FDA of the NDA submission of satraplatin for hormone-refractory prostate cancer, that the rolling NDA filing will be completed by end of the year, that other trials evaluating the effects of satraplatin in combination with radiation therapy, in combination with other cancer therapies and in various other cancers will be initiated and any statements that relate to the intent, belief, plans or expectations of Spectrum or its management, or that are not a statement of historical fact. Risks that could cause actual results to differ include the possibility that our existing and new drug candidates, may not prove safe or effective, the possibility that our existing and new drug candidates may not receive approval from the FDA, and other regulatory agencies in a timely manner or at all, the possibility that our existing and new drug candidates, if approved, may not be more effective, safer or more cost efficient than competing drugs, the possibility that price and other competitive pressures may make the marketing and sale of our generic drugs not commercially feasible, the possibility that our efforts to acquire or in-license and develop additional drug candidates may fail, our lack of revenues, our limited experience in establishing strategic alliances, our limited marketing experience, our limited experience with the generic drug industry, our dependence on third parties for clinical trials, manufacturing, distribution and quality control and other risks that are described in further detail in the Company’s reports filed with the Securities and Exchange Commission. We do not plan to update any such forward-looking statements and expressly disclaim any duty to update the information contained in this press release except as required by law.

Spectrum Pharmaceuticals, Inc.
http://www.spectrumpharm.com/

SCHWARZ PHARMA Highlights The Results Of 13 Lacosamide Data Presentations At North American Regional Epilepsy Congress In San Diego

As part of its ongoing scientific research program for lacosamide, SCHWARZ PHARMA presented an overview of comprehensive pre-clinical and clinical data at the North American Regional Epilepsy Congress, including a positive Phase III trial, which suggested that lacosamide was both efficacious and well tolerated when added to drug regimens of subjects previously uncontrolled on 1-3 antiepileptic drugs (AEDs). Other highlights included data presentations on lacosamide’s mode of action, pre- clinical efficacy for various seizure types and neurological disorders, and Phase II and III clinical trials investigating lacosamide for epilepsy and painful distal diabetic neuropathy.

“The studies presented at the North American Regional Epilepsy Congress strongly support the clinical development of lacosamide, a novel compound with a dual mode of action, for both epilepsy and diabetic neuropathic pain,” said Iris Loew-Friedrich, MD, PhD, member of the Executive Board SCHWARZ PHARMA AG. “The Phase III studies presented at the meeting will become part of the marketing authorization applications for lacosamide in both the European Union and United States.”

Pre-Clinical Data Summary

Following are highlights from the pre-clinical data presentations:

— Lacosamide appears to have two novel modes of action. Unlike other drugs that treat epilepsy and diabetic neuropathic pain, lacosamide selectively enhances slow inactivation of voltage-gated sodium channels, and modulates collapsin response mediator protein 2 (CRMP-2)

— Lacosamide was shown to have potent and broad neuroprotective effects in-vitro and in animal models, which may positively influence the pathogenesis of epilepsy with long-term use

— Combinations of lacosamide with other antiepileptic drugs were associated with potential synergistic anticonvulsant effects

— Lacosamide was highly-active in multiple pre-clinical models of different seizure types and attenuation of seizure spread. Additionally, lacosamide did not induce negative central nervous system (CNS) effects at therapeutic doses

— Lacosamide showed potent and broad effects in animal models for essential tremor, tardive dyskinesia, schizophrenia, and anxiety

Clinical Data Summary

Following are highlights from the clinical data presentations:

Epilepsy

— A pivotal Phase III trial evaluating oral lacosamide 200 and 400 mg/day as adjunctive therapy in adults with uncontrolled partial seizures demonstrated statistically significant and clinically relevant improvements over placebo. Lacosamide was generally well tolerated when administered concomitantly with 1-3 antiepileptic drugs

— In a multi-center, open-label, Phase III trial, the safety profile for lacosamide solution for intravenous infusion was shown to be comparable to oral lacosamide tablets and was generally well tolerated

— An interim analysis of an ongoing, open-label, multi-center Phase II extension trial (SP 615) suggests that lacosamide greater than or equal to 200 mg/day may be well tolerated as long-term adjunctive treatment for patients with partial seizures

— A pharmacokinetic analysis from a multi-center, double-blind trial showed that concomitant antiepileptic drug plasma concentrations were not affected by oral lacosamide treatment

Diabetic Neuropathic Pain

— A multi-center, double-blind, placebo-controlled Phase III trial demonstrated that lacosamide 400 mg/day significantly reduced pain scores in patients with diabetic neuropathy, and the effect was sustained over an 18-week treatment period

About Lacosamide

Lacosamide is a novel, investigational compound that has been studied in Phase III trials. The results suggest efficacy in treating both epilepsy and painful diabetic neuropathy. Studies have indicated that lacosamide works through two unique and separate modes of action. Unlike traditional AEDs that affect sodium channel fast-inactivation, lacosamide is believed to selectively enhance slow-inactivation, thus reducing abnormal neuronal transmission in the brain. Additionally, lacosamide acts on a protein involved in neuronal growth (CRMP-2). The interaction of lacosamide with CRMP-2 may prevent the formation of abnormal neuronal connections in the brain. This could have a possible effect on the underlying disease.

In epilepsy patients, lacosamide was generally well tolerated. Dizziness, headache and nausea were the most commonly reported side effects across all treatment groups. In DNP patients, incident rates of individual adverse events were similar between the placebo, 200 and 400 mg/day groups, but were higher with the 600 mg/day dose. The most common treatment emergent adverse events included dizziness, nausea, fatigue and headache.

About Epilepsy

“Epilepsy” is the name for a whole group of serious disorders, which may be inherited or caused by other factors such as trauma. An abnormal increase in the activity of the central nervous system leads to epileptic seizures, which are usually manifested as shaking or convulsions with impaired consciousness. Approximately 5-8% of the population will have a seizure once in their life. About 0.5-1.0% of the population will have recurrent seizures, which is necessary to diagnose epilepsy. Anticonvulsants serve to prevent epileptic seizures and are most often used as long-term therapy.

About Diabetic Neuropathic Pain

Approximately 11 million patients worldwide suffer from diabetic neuropathic pain (DNP), a common and chronic condition associated with blood glucose levels that are or have been out of control. DNP is thought to result from permanently damaged nerves, which cause sensations such as numbness, tingling, burning or aching in the extremities. For many patients, diabetic neuropathic pain is intolerable. Daily life activities and quality of life can be severely affected. Patients with DNP often require long-term treatment to manage the pain associated with the condition.

SCHWARZ PHARMA (headquartered in Monheim, Germany) is a stock listed company with approximately 4,400 employees worldwide. The company develops novel medicines in the therapeutic areas of the central nervous system. Furthermore it markets innovative drugs focused to treat cardiovascular and gastro-intestinal diseases. In 2005 the SCHWARZ PHARMA group achieved global sales of nearly euro 1 billion. The company has a strong international presence with subsidiaries in Europe, USA and Asia.

This press release contains forward-looking statements based on current plans, estimates and beliefs of the management of SCHWARZ PHARMA AG. Such statements are subject to risks and uncertainties that may cause actual results to be materially different from those that may be implied by such forward-looking statements contained in this press release. Important factors that could result in such differences include: changes in general economic, business and competitive conditions, effects of future judicial decisions, changes in regulation affecting SCHWARZ PHARMA AG, exchange rate fluctuations and hiring and retention of its employees.

SCHWARZ PHARMA
http://www.schwarzusa.com

Barr Receives Approval For Allegra(R) Capsules

Barr Pharmaceuticals, Inc. (NYSE: BRL) today announced that its subsidiary Barr Laboratories, Inc. has received final approval from the U.S. Food and Drug Administration (FDA) for its generic version of Aventis Pharmaceuticals’ Allegra(R) (Fexofenadine Hydrochloride) Capsules, 60 mg. The Company is the first applicant to file an Abbreviated New Drug Application (ANDA) containing a paragraph IV patent challenge on the patents related to the Allegra capsule product, and is entitled to 180 days of marketing exclusivity on the product.

Allegra (Fexofenadine Hydrochloride) is indicated for the relief of symptoms associated with seasonal allergic rhinitis and for the treatment of uncomplicated skin manifestations of chronic idiopathic urticaria in adults and children 6 years of age and older. Allegra (Fexofenadine Hydrochloride) Capsules, 60 mg, which had annual sales of approximately $14,000 based on IMS data for the twelve months ended May 2005, is no longer marketed by Aventis.

Barr filed an ANDA for Fexofenadine Hydrochloride Capsules, 60 mg, in May 2001. Following receipt of notice of acceptance from FDA, Barr notified Aventis of its ANDA filing. Aventis filed suit in the United States District Court for the District of New Jersey seeking to prevent approval of Barr’s ANDA until after the expiration of various patents, the last of which expires in 2017.

In July 2004, Barr announced that the U.S. District Court in New Jersey had granted summary judgment of non-infringement with respect to three patents in the Company’s patent challenge litigation involving Allegra (Fexofenadine Hydrochloride). On April 1, 2005, the Company announced that the Court granted summary judgment of invalidity on an additional patent in the case.

The court has yet to rule on five patents related to the Allegra tablet and capsule products remaining in the litigation — three method-of-use patents and two raw material patents. While no trial date has been set, Barr anticipates that the case may be ready for trial early in 2006.

Barr Pharmaceuticals, Inc. is a holding company whose principal subsidiaries, Barr Laboratories, Inc. and Duramed Pharmaceuticals, Inc., develop, manufacture and market generic and proprietary pharmaceuticals.

Forward-Looking Statements

Except for the historical information contained herein, the statements made in this press release constitute forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Forward-looking statements can be identified by their use of words such as “expects,” “plans,” “projects,” “will,” “may,” “anticipates,” “believes,” “should,” “intends,” “estimates” and other words of similar meaning. Because such statements inherently involve risks and uncertainties that cannot be predicted or quantified, actual results may differ materially from those expressed or implied by such forward-looking statements depending upon a number of factors affecting the Company’s business. These factors include, among others: the difficulty in predicting the timing and outcome of legal proceedings, including patent-related matters such as patent challenge settlements and patent infringement cases; the outcome of litigation arising from challenging the validity or non- infringement of patents covering our products; the difficulty of predicting the timing of FDA approvals; court and FDA decisions on exclusivity periods; the ability of competitors to extend exclusivity periods for their products; our ability to complete product development activities in the timeframes and for the costs we expect; market and customer acceptance and demand for our pharmaceutical products; our dependence on revenues from significant customers; reimbursement policies of third party payors; our dependence on revenues from significant products; the use of estimates in the preparation of our financial statements; the impact of competitive products and pricing on products, including the launch of authorized generics; the ability to launch new products in the timeframes we expect; the availability of raw materials; the availability of any product we purchase and sell as a distributor; the regulatory environment; our exposure to product liability and other lawsuits and contingencies; the increasing cost of insurance and the availability of product liability insurance coverage; our timely and successful completion of strategic initiatives, including integrating companies and products we acquire and implementing our new enterprise resource planning system; fluctuations in operating results, including the effects on such results from spending for research and development, sales and marketing activities and patent challenge activities; the inherent uncertainty associated with financial projections; changes in generally accepted accounting principles; and other risks detailed from time-to-time in our filings with the Securities and Exchange Commission, including in our Annual Report on Form 10-K for the fiscal year ended June 30, 2004.

The forward-looking statements contained in this press release speak only as of the date the statement was made. The Company undertakes no obligation (nor does it intend) to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except to the extent required under applicable law.

Barr Pharmaceuticals, Inc. news releases are available free of charge through PR Newswire’s News On-Call site at http://www.prnewswire.com/comp/089750.html. Barr news releases and corporate information are also available on Barr’s website (http://www.barrlabs.com). For complete indications, warnings and contraindications, contact Barr Laboratories’ Product Information Department at 1-800-Barr Lab.

Carol A. Cox
Barr Laboratories, Inc.
+1-201-930-3720
ccox@barrlabs.com
http://www.barrlabs.com

First-ever Genomic Test Predicts Which Lung Cancer Patients Need Chemotherapy To Live

Duke University Medical Center scientists have developed the first-ever genomic test to predict which patients with early-stage lung cancer will need chemotherapy to live and which patients can avoid the toxic regimen of drugs.

The test has the potential to save thousands of lives each year by recommending chemotherapy for patients who are currently advised against it, said the test’s developers at Duke’s Institute for Genome Sciences & Policy.

The test’s promising results have initiated a landmark multi-center clinical trial, to be led by Duke investigators next year. Patients with early-stage non-small cell lung cancer, the most common and fatal form of cancer, will receive the genomic test and its results will determine their treatment.

The new test, called the Lung Metagene Predictor, scans thousands of genes to identify patterns of gene activity in individual tumors that indicate a patient is likely to suffer a recurrence of disease. Recurrent tumors are typically fatal, so identifying at-risk patients is critical to properly treating them, said the Duke researchers.

“Using the unique genomic signatures from each tumor, our new test predicted with up to 90 percent accuracy which early-stage lung cancer patients would suffer a recurrence of their cancer and which patients would not,” said Anil Potti, M.D., an assistant professor of medicine and lead author of the study. “We now have a tool that can be used to move these high-risk patients from the ‘no chemotherapy’ group into the aggressive treatment group.”

The researchers will publish their findings in the August, 2006, issue of the New England Journal of Medicine. The research was funded by the National Institutes of Health.

The genomic test can theoretically apply to any cancer, but the Duke team focused its effort on lung cancer because the survival rate is just 15 percent. Lung cancer now kills more Americans each year than breast, prostate and colorectal cancers combined. But toxic chemotherapy drugs are prescribed only to patients with relatively large and aggressive tumors.

Early-stage patients – those with small, stationary tumors – are considered at low risk of recurrence. Hence, they only receive surgery but not chemotherapy. The dilemma, said Potti, is that a third or more of early-stage patients who appear to be at low risk will experience a recurrent tumor.

“Until now, there simply has been no way to identify the 30 percent to 40 percent of early-stage lung cancer patients who would experience a recurrence,” Potti said. “Now, with our test, we can say with confidence that we can identify this group of patients so they can be treated accordingly.”

The upcoming trial is the first to use a genomic test to select treatment options for individual lung cancer patients, said David Harpole, M.D., a professor of thoracic surgery at Duke and principal investigator of the upcoming clinical trial. The trial, to begin within six months, will enroll more than 1,000 patients at multiple centers in the United States and Canada.

“If we can use the test to increase patient survival by even 5 percent, we would save 10,000 lives a year,” Harpole said.

The Duke researchers developed the test by analyzing the activity of genes from early-stage lung cancer patients whose disease outcomes were known. The Duke scientists then validated the genomic test in 129 patients by comparing the test’s predictions with the patient’s actual outcomes. The test predicted their risk of recurrence with 90 percent accuracy, the study showed.

If proven to be effective in the clinical trial, the test will replace the current method of assessing risk, which is imprecise and provides only a broad estimate of a patient’s risk, said Joseph Nevins, Ph.D., a professor of molecular genetics at Duke and senior author of the study being reported.

Physicians now assign each patient to a clinical “stage” based on the size of the patient’s tumor, whether it has invaded lymph nodes and whether it has spread to other organs. They use this staging method to prescribe the best treatment options. But staging parameters are general, at best, and do not accurately define who should receive chemotherapy, Nevins said.

“Instead of placing all patients with small tumors in the same early-stage category, as physicians currently would do, we can now assess their risk based on the tumor’s genomic profile,” Nevins said. “The current system of ’staging’ lung cancer tumors will eventually become obsolete.”

To employ the test, physicians take a sample of the tumor as it is removed during surgery. They extract its “messenger RNA,” which represents the activity of thousands of genes in the tumor. Messenger RNA translates a gene’s DNA code into proteins that run the cell’s activities. Hence, it is a barometer of a gene’s activity level inside the cell.

Scientists label the messenger RNA with fluorescent tags. The fluorescent RNA is then placed on a tiny glass slide, called a gene chip. There, it binds to its complementary DNA sequence on the gene chip.

When scanned with special light, the fluorescent RNA emits a telltale luminescence that demonstrates how much RNA is present on the chip – and thus which genes are most active in a given tumor. The physicians then use a rigorous statistical analysis to assess the relative risk of large grouping of genes, called metagenes, which have similar characteristics.

The test generates a risk “number” for each patient. If their risk exceeds 50 percent, the patient is advised to get chemotherapy.

“This new genomic test is a clear example of personalized medicine, where we use the unique molecular characteristics of each patient’s tumor to guide treatment decisions,” said Geoffrey Ginsburg, M.D., Ph.D., a professor of medicine and co-author of the study.

Eventually, physicians will use genomic tests not only to predict patient outcomes, but also to select the individual drugs that will best match a tumor’s molecular makeup, Ginsburg said.

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Other collaborators on the study being reported include, from Duke, Sayan Mukherjee, Holly Dressman, Andrea Bild, Rebecca Petersen, Jason Koontz, Michael Kelley and Mike West; Robert Kratzke of the University of Minnesota; and Mark Watson of Washington University in St. Louis.

Contact: Marla Vacek Broadfoot
Duke University Medical Center

PDE3B Regulates Energy Levels In Mice

Insulin acts on many cells to exert its control over the amount of energy that is available to the body. When cells become resistant to the effects of insulin, type 2 diabetes and other metabolic disorders can develop. Understanding the molecular pathways by which insulin affects the different cells might provide clues as to why insulin resistance develops. Now, in a study appearing in the December issue of the Journal of Clinical Investigation, researchers from the National Heart, Lung and Blood Institute have shown that a protein known as PDE3B has a non-redundant role in some of the molecular pathways activated by insulin in mice.

Young Hun Choi and colleagues generated mice lacking PDE3B and found that lipid metabolism, which is regulated by insulin, was dysregulated in these animals. Although when stimulated, PDE3B-deficient mice secreted more insulin than normal mice, the PDE3B-deficient mice were less able to control their blood glucose levels and to regulate lipid metabolism. This demonstration of insulin resistance in PDE3B-deficient mice indicates that PDE3B has an irreplaceable role in the molecular pathways that are activated by insulin. The authors therefore suggest that altered expression or activity of PDE3B might have a role in the development of insulin resistance in humans.

TITLE: Alterations in regulation of energy homeostasis in cyclic nucleotide phosphodiesterase 3B-null mice.

AUTHOR CONTACT:
Young Hun Choi
National Institutes of Health, Bethesda, Maryland, USA.

View the PDF of this article at: http://https://www.the-jci.org/article.php?id=24867

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JCI table of contents: December 1, 2006

Contact: Karen Honey
Journal of Clinical Investigation

New factor implicated in allergy and asthma attacks

Discovery that oxidative stress from pollen is as important as antigen exposure could lead to new therapies –

For a person with allergies or asthma, breathing in pollen can be a very bad thing. Within minutes of inhalation by someone sensitive to their effects, these tiny particles can trigger severe inflammation of the respiratory passages, producing uncontrollable sneezing, coughing, or extreme shortness of breath — symptoms agonizingly familiar to those who suffer from allergy and asthma attacks.

Scientists have long assumed that they know how pollen produces such debilitating responses. They blame an overreaction by the body’s immune system, set off by proteins known as antigens, which are found on the surface of pollen particles–an inappropriate activation of the normal “antigen-mediated” immune response the body uses to defend itself against viruses and bacteria.

Now, though, researchers at the University of Texas Medical Branch at Galveston have discovered strong evidence that an additional factor is necessary to cause the severe respiratory inflammation involved in an allergy or asthma attack. This factor is the damage caused by chemically hyperactive molecules known as “reactive oxygen species,” which are spawned by interactions between a single pollen-carried enzyme and the cells that line airways. And, the researchers say, if an effective way can be found to reduce that damage–called “oxidative stress”–new and powerful allergy and asthma therapies may result.

“There has been a lot of discussion about oxidative stress exacerbating asthma and allergies, but this is the first direct evidence that oxidative stress is required to induce a robust inflammation, and the first demonstration that a source of that stress is right there in the pollen itself,” said UTMB associate professor Istvan Boldogh, a lead author of a paper on the research that will be published online August 1 in the Journal of Clinical Investigation.

Boldogh and the other lead authors –Attila Bacsi, Nilesh Dharajiya and Barun Choudhury, along with UTMB researchers Tapas Hazra, Sankar Mitra, Randall Goldblum and Sanjiv Sur and Rafeul Alam (formerly of UTMB and now director of the Division of Allergy and Immunology at the National Jewish Medical and Research Center in Denver)–worked nearly four years conducting extensive test-tube and lab-mouse experiments to prove the paradigm-shifting “two-signal concept” in detail. They zeroed in on a key enzyme known as NADPH oxidase, which they identified in grains of pollen produced by ragweed and 38 other plant pollens and molds linked to allergy and asthma attacks. Within minutes of exposure, ragweed pollen or its extract containing NADPH oxidase produce damaging reactive oxygen species in cell culture and, in experiments with mice, in their lungs and airway lining fluid. The resulting oxidative stress, Boldogh said, almost immediately prompted the production of inflammatory immune signaling molecules and accumulation of inflammatory cells, a downstream event common to lung and other type of allergic inflammations. By contrast, ragweed pollen extract from which NADPH oxidase had been removed produced no reactive oxygen species, and resulted in a much smaller increase in numbers of inflammatory immune cells.

“We showed that you need both oxidative stress and antigenic exposure to get a robust allergy or asthma attack, and also that the first few minutes of the exposure are critical,” Boldogh said. “The antigen exposure has to happen in parallel with oxidative stress, and having both components in the pollen makes that possible.” These two signals play a vital role in inducing allergic inflammation.

These findings suggest that antioxidant substances may be useful in forestalling allergy or asthma attacks. Sur and Boldogh predict that this new paradigm of initiation of allergic inflammation will lead to extensive research into discovery of novel compounds that either specifically inhibit pollen NADPH oxidases or those that prevent or inhibit oxidative stress in the lungs induced by this enzyme.

Past studies report contradictory results concerning the effectiveness of antioxidants such as Vitamin C in reducing airway inflammation. Those contradictions, Dharajiya pointed out, are resolved by the evidence that pollen brings both NADPH oxidase and antigens into the airways, making airway antioxidant levels the critical factor. “The antioxidant has to be there when the person is exposed, and if the antioxidant level is not sufficient, it won’t eliminate this oxidative insult.”

Because antioxidant compounds are quickly metabolized in the lungs and airways, it may be necessary to deliver them every few hours via an inhaler. Boldogh and Sur suggested that it is now important to develop longer-lived antioxidant. “If we can find an antioxidant with a longer half-life, it could be really very effective in asthma and allergy treatment and also prevention,” Boldogh said.

This research was supported by a grant to Sur and Boldogh from the National Heart Lung and Blood Institute, UTMB’s National Institute of Environmental Health Sciences Center (Sur, Alam, Boldogh), and National Heart Lung and Blood Institute Proteomics Initiative (Sur).

For more information or to schedule an interview, request a digital photo or arrange a taped or live television interview via UTMB’s satellite services, please call the media hotline.

Jim Kelly
jpkelly@utmb.edu
409-772-8791
University of Texas Medical Branch at Galveston
http://www.utmb.edu

Novel Treatment Approach For Lung Cancer At The University Of Pittsburgh Medical Center (UPMC) Cancer Centers Targets Tumors While They Are Moving

Clinicians at the University of Pittsburgh Medical Center (UPMC) Cancer Centers successfully treated a lung cancer patient in her mid-fifties using a new more precise technique that combines image-guided radiotherapy (IGRT) with respiratory gating to zero in on her tumor while adapting for breathing motion. The new tissue sparing procedure was made possible using advanced imaging and treatment technology from Varian Medical Systems (NYSE: VAR) of Palo Alto, California.

The UPMC medical team specially designed the patient’s sophisticated treatment to protect her heart and esophagus as well as the healthy parts of her lung. The Dynamic Targeting IGRT(TM) treatment was delivered using Varian’s powerful Trilogy(TM) linear accelerator equipped with an On-Board Imager(TM) for monitoring tumor motion and the RPM(TM) respiratory gating system for synchronizing beam delivery with the patient’s natural breathing cycle.

“We had to be concerned about compromising this patient’s ability to breathe,” said Dwight Heron, MD, vice chairman of clinical affairs, department of radiation oncology, UPMC Cancer Centers. “As a result, it was vitally important to minimize the exposure of radiation to the surrounding healthy lung tissue.” Typical side effects from lung cancer treatments include inflammation of the esophagus or healthy lung tissue, but the new procedure has made it possible to reduce the risk of complications while increasing the chances of eradicating the tumor.

Using Images to Fine-Tune Patient Positioning

To position the patient for treatment each day, the UPMC clinical team used the On-Board Imager to generate high-quality radiographic X-ray images of the targeted area immediately before each treatment session. With the push of a button, the patient was then repositioned, based on changes detected in the daily images. Periodically, the UPMC team also generated three-dimensional cone-beam CT images, to further verify that the patient had been moved into the best position for the ultra-precise treatment.

Dealing with Tumor Motion

An imaging study of the patient revealed that her tumor moved 1.2 centimeters with every breath she took. Traditionally, Heron said, tumor motion of this magnitude would have compelled him to treat an additional margin of about 1 to 1.5 centimeters around the tumor, in order to ensure that the treatments fully encompassed the tumor. In this patient’s case, he felt that this would have meant irradiating too large a volume of healthy tissue in the upper lobe of her left lung. RPM(TM) respiratory gating technology helped him solve the problem.

“We set our RPM respiratory gating system to deliver the treatment beam only during a particular part of her respiratory cycle, when her tumor moved the least,” Heron said. “This happened when she was about halfway through her exhalation — the tumor was virtually motionless at that point, so we could target it very accurately. Using this approach, we were able to decrease the treatment margin to half a centimeter,” Heron said.

“Technologies like the Trilogy(TM) machine, with the On-Board Imager and respiratory gating make it possible for us to adopt a truly personalized approach to cancer care,” Heron added. “With these tools, we can make individual adjustments each day based on what we’re seeing that day. To have all of these capabilities fully integrated with the treatment machine has given us the power to truly tailor cancer treatment for each and every patient.”

Heron and his clinical team at UPMC Shadyside have treated over 100 lung cancer cases using Dynamic Targeting IGRT technology since December of 2005. According to the American Cancer Society, there are approximately 174,000 new cases of lung cancer diagnosed in the U.S.each year, and surgery has been the most common form of treatment for localized tumors. “Up to now, most early stage lung cancer patients have been treated with chemotherapy or surgery — very few received radiation, because accurate targeting was difficult to achieve,” said Dow Wilson, president of Varian’s Oncology Systems business.

”The success of this work at UPMC suggests that more and more patients can benefit from noninvasive radiotherapy procedures for some forms of lung cancer.”

ABOUT UPMC CANCER CENTERS

UPMC Cancer Centers, one of the largest integrated community networks of cancer physicians and health care specialists in the country, allows patients to receive the highest level of cancer care without having to leave their communities. Working in tandem with the University of Pittsburgh Cancer Institute (UPCI), UPMC Cancer Centers offers patients the latest advances in cancer prevention, detection, diagnosis and treatment at locations throughout Western Pennsylvania and sounding areas.

ABOUT VARIAN MEDICAL SYSTEMS

Varian Medical Systems, Inc., of Palo Alto, California is the world’s leading manufacturer of integrated cancer therapy systems, which are treating thousands of patients per day. The company is also a premier supplier of X- ray tubes and flat-panel digital subsystems for imaging in medical, scientific, and industrial applications. Varian Medical Systems employs approximately 3,300 people who are located at manufacturing sites in North America and Europe and in its 55 sales and support offices around the world. Additional information is available on the company’s investor relations web site at http://www.varian.com .

FORWARD LOOKING STATEMENTS

Statements in this press release regarding future business, events, plans, objectives, expectations, estimates, and other similar matters, including, but not limited to, statements using the terms “can be used,” “plan to,” will enable,” “are likely to,” “is becoming,” and “have the potential to” constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements contained in this press release are subject to risks and uncertainties that could cause actual results to differ materially from those anticipated, including, but not limited to, the risks described in the company’s Annual Report on Form 10-K and other reports filed from time to time by the Company with the Securities and Exchange Commission. These forward-looking statements represent the Company’s judgment as of the date of this press release. The Company assumes no obligation to update or revise these forward-looking statements because of new information, future events, or otherwise.

Varian Medical Systems
http://www.varian.com

LifeMasters Provides Healthy Eating Tips To Help Individuals Manage Chronic Conditions During The Holidays

The holiday grazing season sparks weight gain worries for the average American, but for individuals with chronic conditions, the worries and health risks can be more serious. Holiday foods high in fat, sugar, calories and sodium can contribute to symptoms that challenge their management of chronic conditions.

“The temptation of large dinners and baked goods may cause overindulging, and the cold weather discourages people from exercising,” said C. Rene Hughes, RN, MS, CV/ANP, Clinical Product Manager, at LifeMasters Supported SelfCare, Inc., a leading provider of disease management programs and services in the nation. “Holiday eating can present challenges for people with chronic conditions. People with diabetes can skyrocket their blood glucose levels by eating too many carbohydrates and for those dealing with congestive heart failure or hypertension, consuming foods high in sodium can lead to fluid retention and aggravation of high blood pressure.”

Hughes offers the following tips to reference during the holidays to help improve management of chronic conditions and enjoy a happy and healthy holiday:

LifeMasters Tips for a Healthy Holiday:

1. Think ahead: Don’t skip meals. Keep consistent meal times when possible as eating at your regular meal times can help prevent overeating.

2. Manage size: Practice portion control by limiting meals to one serving and eating slowly so the brain registers the feeling of being full.

3. Avoid ingredients that can affect your condition: Read the nutritional facts on package labels and ask about the ingredients of served food to avoid high amounts of fat, sugars, carbohydrates and sodium.

4. Know your body: For people with diabetes, increase glucose monitoring during the holiday season. It may be helpful to check your blood glucose levels before holiday events, meals and parties. Fatigue during the holiday season is common. Prevent fatigue by getting a good night’s sleep. An occasional nap during the day may be helpful too.

5. Exercise frequently: Walk or do low-intensity workouts to burn up excess calories and increase energy levels. For people with diabetes, exercise helps control blood glucose levels. Attend light workout classes like Tai Chi or schedule “walk breaks” during the work day. If it’s cold outside, walking at your local mall or taking the stairs instead of the elevator are good alternatives for activity. Regular exercise can also help reduce the stress that the holiday season brings.

6. Limit your alcohol: Alcohol is high in calories. The amount of calories varies with the type and amount of an alcoholic beverage. Keep to sensible drinking. Don’t drink on an empty stomach. Enjoy your drink with your meal.

About LifeMasters Supported SelfCare

LifeMasters Supported SelfCare, Inc. is a leading provider of disease management programs and services that create health partnerships among individuals, their physicians and payors. Its mission is to empower individuals to achieve and maintain optimal health. The programs improve quality of care for people with chronic illnesses, reduce chronic-disease costs for payors and provide decision-support tools for physicians. LifeMasters offers programs for individuals with diabetes, congestive heart failure (CHF), coronary artery disease (CAD), chronic obstructive pulmonary disease (COPD) hypertension and asthma (all of which are fully accredited by the National Committee for Quality Assurance (NCQA) and URAC) and musculo-skeletal pain. LifeMasters’ programs are holistically focused, support co-morbidities such as depression and facilitate lifestyle changes such as smoking cessation and weight loss. LifeMasters provides services to more than 650,000 people throughout the nation.

Founded in 1994 by a physician, LifeMasters works with some of the nation’s leading health plans, employers, retirement systems and governmental organizations, including Aetna, BlueCross BlueShield of Tennessee, State Teachers Retirement System of Ohio, Florida’s Agency for Health Care Administration (Medicaid) and CMS. More information about LifeMasters can be found at http://www.lifemasters.com or by calling 1-800-777-1307.

LifeMasters Supported SelfCare, Inc.
http://www.lifemasters.com