Allergy Sufferers Offered Longer Relief With Fewer Shots Using Experimental Ragweed Therapy

Americans accustomed to the seasonal misery of sneezing, runny noses and itchy, watery eyes caused by ragweed pollen might one day benefit from an experimental allergy treatment that not only requires fewer injections than standard immunotherapy, but leads to a marked reduction in symptoms that persists for at least a year after therapy has stopped, according to a new study in the October 5 issue of i The New England Journal of Medicine (NEJM). The research was sponsored by the Immune Tolerance Network, which is funded by the National Institute of Allergy and Infectious Diseases (NIAID) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), both components of the National Institutes of Health (NIH), and the Juvenile Diabetes Research Foundation International.

“As many as 40 million Americans suffer from seasonal allergies caused by airborne pollens produced by grasses, trees and weeds,” says NIH Director Elias A. Zerhouni, M.D. “Finding new therapies for allergy sufferers is certainly an important research goal.”

“This innovative research holds great promise for helping people with allergies,” says NIAID Director Anthony S. Fauci, M.D. “A short course of immunotherapy that reduces allergic symptoms over an extended period of time will significantly improve the quality of life for many people.”

Ragweed is one of the most common pollens in the United States and is prevalent in the Northeast, Midwest and the South. In Baltimore, where the NEJM study was conducted, the ragweed pollen season lasts from mid-August to October.

Physicians treat people suffering from mild and moderate ragweed allergies with antihistamines or nasal corticosteroids. However, when people with allergies do not respond to these treatments or experience severe symptoms, the next therapeutic option is a course of subcutaneous injections of the allergen, which is called allergen immunotherapy. Although this standard immunotherapy is often effective, it has two major drawbacks. First, it can cause systemic allergic reactions, such as anaphylaxis, a hypersensitivity reaction that can lead to severe and sometimes life-threatening physical symptoms. Second, to provide long-lasting relief, standard immunotherapy may require frequent injections over a 3- to 5-year period. The large number of injections over such an extended period of time often results in many people not completing the treatment.

In the study detailed in NEJM, lead investigator Peter Creticos, M.D., medical director of the Johns Hopkins Asthma and Allergy Center in Baltimore, and his research team found that an investigational therapy based on the major ragweed allergen, Amb a 1, coupled to a unique short, synthetic sequence of DNA that stimulates the immune system, reduced allergy symptoms in adults for at least one year when given just once a week over a 6-week period. The therapeutic agent was provided by Dynavax Technologies Corp., based in Berkeley, CA.

“For almost 100 years, we’ve been using the tedious process of giving allergy sufferers one to two shots a week for up to 4 to 5 years to ensure its success,” Dr. Creticos says. “This study is an important immunotherapy advance in that we’ve shown you can induce long-lasting relief from allergic rhinitis with just a few weeks of injections.”

The study initially involved 25 adult volunteers, ages 23 to 60, with a history of seasonal allergic rhinitis, positive skin test reactions to ragweed pollen, and an immediate reaction when nasally challenged with ragweed. Prior to the start of the 2001 fall ragweed season, the study participants received six injections, each a week apart, of either the investigational therapy in increasingly higher doses or a placebo. They received no other injections throughout the course of the study. Fourteen volunteers received the study drug; 11 were given the placebo. The therapy was well-tolerated and caused only limited local reactions, which required neither medication nor change in treatment dose. No clinically significant, therapy-related adverse events occurred.

Throughout the 2001 and 2002 ragweed seasons, the volunteers were monitored for allergy-related symptoms, including the number of sneezes and the degree of post-nasal drip, allergy medication use and quality-of-life scores. Compared with the placebo recipients, the group that received the therapy experienced dramatically better outcomes that continued throughout the 2002 ragweed season even though therapy ended one year earlier.

Clearly, the regimen of only six injections showed therapeutic promise when compared with the current therapy, the study authors note. However, because the results are based on a small number of volunteers and the long-term safety of the therapy is unknown, they say additional clinical trials with longer-term follow-up to adequately assess the therapy’s safety and effectiveness are necessary.

How the experimental therapy relieves ragweed allergy symptoms is not fully understood at this time. When exposed to ragweed pollen, people who are allergic to ragweed experience an increase in IgE (immunoglobulin) antibodies; immunotherapy blocks this increase in IgE. Researchers believe the experimental therapy tempers the release of immune regulatory proteins called cytokines, which blocks increases in the level of IgE antibodies.

“Using ragweed as a model allergen system with a predictable seasonal pattern of symptoms and pollen counts, it is possible to correlate pollen levels with symptoms and measure treatment effects on symptoms. This enables us to better understand immune response to allergens and serves as an approach to similar therapies to manage other allergic reactions for which there are currently no treatments, such as food allergies,” says Marshall Plaut, M.D., chief of the Allergic Mechanisms Section of NIAID’s Division of Allergy, Immunology and Transplantation.

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NIAID is a component of the National Institutes of Health. NIAID supports basic and applied research to prevent, diagnose and treat infectious diseases such as HIV/AIDS and other sexually transmitted infections, influenza, tuberculosis, malaria and illness from potential agents of bioterrorism. NIAID also supports research on basic immunology, transplantation and immune-related disorders, including autoimmune diseases, asthma and allergies.

The National Institutes of Health (NIH)–The Nation’s Medical Research Agency–includes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov/.

Reference: PS Creticos et al. Immunotherapy with a ragweed-TLR9 agonist vaccine for allergic rhinitis. The New England Journal of Medicine DOI: 10.1056/NEJMoa052196 (2006).

News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov/.

Contact: Kathy Stover
NIH/National Institute of Allergy and Infectious Diseases

EU Health Research Must Prioritise Allergies

European public health experts are concerned because “allergic diseases” in all their different aspects – from hay fever to fatal attacks of asthma or reactions to peanuts – are not included in the health priorities of the EU research programme. While allergies are mentioned among the food research priorities, the absence of wider allergy problem as a top concern in health research agenda threatens to comprise overall progress in the understanding of this complex condition.

  Paul van Cauwenberge, Coordinator of GAІLEN (Global Allergy and Asthma European Network), says that if the European Union does not make it a top concern in health research, researchers and practitioners may fail to contain the allergy epidemic. (1)

  “GAІLEN has helped to demonstrate the magnitude of this public health problem and begun to find the solutions,” says Prof. van Cauwenberge of the University of Ghent, Belgium. “But if allergic diseases are not included as a health priority in the next EU framework programme FP7 (2), we are much less likely to build the overall understanding we need to help control this epidemic through effective prevention and treatment.” (2)

  While allergy experts welcomed the fact that allergy was considered under the food safety programme in the FP6, they point out that only 8% of allergies in Europe are related to food. Allergic diseases represent a “global” problem in the sense that it has multiple presentations and causes, both genetic and environmental. All the different aspects of the condition and its triggers must be addressed to gain a comprehensive understanding of allergic diseases as a whole.

  Prof. van Cauwenberge believes that politicians and different authorities would want to be alerted to the absence of the overall allergy and asthma problem within the research agenda. “If Europe does not continue to make major investments into integrating and co-ordinating research for an overall vision, we are unlikely to get to grips with why the rapid increase in prevalence is occurring, nor to be able to identify and introduce into clinical practice the best ways to prevent and manage the problem,” he says. 

  Allergic diseases are taking lives daily and creating huge financial costs. According to the World Health Organization, asthma kills someone in Europe every hour. (3) One child in three is allergic today and by 2015, half of the European population may be suffering from one or more allergic condition. (4)

  Estimates have put the financial costs of allergic diseases in Europe at up to 100 billion Euros per year. (4) The personal costs fall particularly heavily on families. Parental fears of a serious attack create anxiety, and even with mild allergies family activities may be limited. Children miss days at school and abstain from sport and other recreational activities. Breathing problems and skin rashes can also harm the self-image of young children, adults and especially teenagers. (5)

  The GAІLEN network has successfully brought together 26 “centres of excellence” in allergies spread through different European countries with the aim to advance the diagnosis, prevention and treatment of allergic diseases. European researchers and doctors involved are now using standardised skin-prick allergy tests so that Europe-wide comparative analysis can take place. In the last few months, a huge European database of comparable longitudinal epidemiological studies, known as birth cohorts, has been finalised so that significantly more reliable analysis can now be made of the multiple genetic and environmental factors causing allergies.

  Working with partner organizations representing allergy specialists and patients’ groups (1), GAІLEN is developing evidence-based guidelines for health professionals and the patients to help them preventing and managing the disease. GAІLEN urges policy makers to support the European Parliament proposal to include allergic diseases in the health priorities of the 7th research framework programme.

  1. GAІLEN – the Global Allergy and Asthma European Network is a “Network of Excellence” funded by the European Union 6th Research Framework Programme. It consists of 26 research centres spread throughout Europe, as well as the European Academy of Allergology and Clinical Immunology (EAACI) and the European Federation of Allergy and Airways Diseases Patients Associations (EFA). More than 30 collaborating centres have joined the network since its launch in 2004.

2. The European Union’s next research programme, known as the Seventh Framework Programme Seven (FP7), begins next year and will run for seven years until 2013.  

3. World Health Report 2003, “Shaping the Future”. World Health Organization.

4. “Allergy: An epidemic that must be stopped”, Position Paper, European Academy of Allergology and Clinical Immunology (EAACI). http://www.efanet.org/activities/eu_policy.html

5. “EU 7th Framework Programme for Research”, Position Paper, European Federation of Allergy and Airways Diseases Patients Associations (EFA). http://www.efanet.org/activities/eu_policy.html

GAІLEN – the Global Allergy and Asthma European Network

http://www.ga2len.net

Children Of Allergy Sufferers Prone To Same Problem

Infants whose parents have allergies that produce symptoms like wheezing, asthma, hay fever or hives risk developing allergic sensitization much earlier in life than previously reported, according to a study by Cincinnati researchers.

The study suggests that the current practice of avoiding skin testing for airborne allergens before age 4 or 5 should be reconsidered, so children in this high-risk group can be detected early and monitored for the possibility of later allergic respiratory disease.

Produced by scientists in UC’s departments of environmental health and internal medicine and at Cincinnati Children’s Hospital Medical Center, the study is reported in the October 2006 edition of The Journal of Pediatrics.

The Cincinnati researchers collected data on 680 children being evaluated for enrollment in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS), sponsored by the National Institute of Environmental Health Sciences (NIEHS), and compared their results with findings in a 2004 Swedish study.

Using the skin-prick allergy test, the Swedish group found that in their general population – which included children whose parents did not suffer from allergies – 7 percent had allergic sensitivity at age 1. The Swedes tested five allergens, two of which were food allergens.

The Cincinnati results, however, showed that 28.4 percent of infants born to “atopic” parents, defined as those with allergies, were sensitized to one or more airborne or food allergens. Eighteen percent were positive to one or more airborne allergens, and 13.7 percent were positive only to an airborne allergen.

According to UC epidemiologist Grace LeMasters, PhD, principal investigator for CCAAPS and the lead author of the report, the Cincinnati findings suggest that the potential for allergic disorders in infancy is underemphasized, “even though sensitization to allergens at younger ages has been shown to be more important than sensitization in late childhood for the development of wheezing symptoms and asthma.”

Working with LeMasters on the study were David Bernstein, MD, Jocelyn Biagini, James Lockey, MD, Patrick Ryan, Manuel Villareal, MD, all UC, and Gurjit Khurana Hershey, MD, PhD, Cincinnati Children’s.

Contact: Amanda Harper
University of Cincinnati

Food Allergies Could Be Fought With Friendly Bacteria In Alcoholic Milkshake

Feeding babies alcoholic milk may help to protect against some food allergies. Kefir, a traditional fermented drink, is consumed in Eastern Europe as a health food, and is often used to wean babies, as it is easily digested. Food allergy prevalence is especially high in children under the age of three, with around 5-8% of infants at risk. Currently the only treatment is avoidance of the problematic food.

“Friendly” bacteria in kefir may play a role in blocking the pathway involved in allergic responses, Lisa Richards reports in Chemistry & Industry, SCI’s fortnightly magazine. Research published 16 October 2006(DOI 10.1002/jsfa2469) in the SCI’s Journal of the Science of Food and Agriculture has shown that the milk drink inhibits the allergen specific antibody Immunoglobulin E (IgE). IgE is involved in immune responses to inactivate organisms that might cause disease. However, in the presence of allergens it can also activate cells responsible for the release of histamine, a chemical which stimulates allergic responses, such as inflammation and constriction of airways.

Ji-Ruei Liu’s team of scientists at the National Formosa University, Yunlin, Taiwan, fed mice the milky drink, and found that after 3 weeks, the amount of ovalbumin (OVA) specific IgE was reduced three-fold. Ovalbumin is an allergenic protein found in egg whites, which cause most allergies in young children. Kefir is also reported to prevent food antigens from passing through the intestinal wall.

Liu believes that the milky drink could be a promising tool in the prevention of allergies. “In the future, maybe we can screen out the certain components (bacterial strains or bioactive peptides) from kefir and utilize them in medicine,” he said.

Also in this weeks Chemistry & Industry, UK firm Rigest are looking for backers to develop an air sanitizing system using an enzyme found naturally in human tears. Lactoperoxidase can attack and kill microbes such as ‘flu viruses and the bacteria responsible for MRSA. The system could be used to sanitize the air in airplanes and hospital sick bays.

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Journal of the Science of Food and Agriculture
About the Journal of the Science of Food and Agriculture The Journal of the Science of Food and Agriculture (JSFA) publishes peer-reviewed original research and critical reviews in these areas, with particular emphasis on interdisciplinary studies at the agriculture/food interface. This international journal covers fundamental and applied research.

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FDA Approves Allegra(R) (fexofenadine Hydrochloride) Oral Suspension For Treatment Of Seasonal Allergy Symptoms And Chronic Idiopathic Urticaria

Sanofi-aventis U.S. (EURONEXT: SAN and NYSE: SNY) announced today that the U.S. Food and Drug Administration (FDA) has approved Allegra(R) (fexofenadine hydrochloride) Oral Suspension for the twice-daily treatment of symptoms associated with seasonal allergies in pediatric patients, 2 to 11 years of age, and for the treatment of chronic idiopathic urticaria in children 6 months to 11 years of age. This approval makes available a safe and effective seasonal allergy treatment option that is non-impairing to pediatric populations as young as 2 years old.

“Until now, parents had few seasonal antihistamine treatment options that were not associated with cognitively impairing adverse side effects,” says Eli Meltzer, M.D., of the Allergy and Asthma Medical Group and Research Center in San Diego. “However, with Allegra Oral Suspension, which does not cause sedation at any dose and is well-established for its antihistamine activity, a medication is now available in a good tasting, easy-to-swallow formulation that can help reduce the seasonal allergy symptoms of children.”

Seasonal allergic rhinitis is a common chronic condition in children. Symptoms of seasonal allergies include nasal drainage, sneezing, watery eyes and itchy nose, eyes and throat. Studies indicate that seasonal allergy inflammation as well as the impairing side effects of older antihistamines can be disruptive to a child and may affect cognitive skills and function.

Allegra Oral Suspension has also been approved for the treatment of chronic idiopathic urticaria (CIU) in twice-daily 30 mg doses for pediatric patients 2 to 11 years of age and twice-daily 15 mg doses for pediatric patients 6 months to 2 years of age. CIU is a rare and bothersome condition characterized by hives lasting more than 6 weeks from an unknown cause. Its symptoms are caused by a reaction to an unknown trigger in the upper layers of the skin. The condition itself may cause severe itching, but is made worse by scratching.

Allegra Oral Suspension will have a berry flavor* and is expected to be available to consumers in time for the 2007 spring allergy season.

Artificial raspberry-cream flavoring

Important Safety Information

Side effects in children 6 months to 5 years old were similar to placebo. Side effects varied by age. The most commonly reported side effects were: vomiting, pyrexia, cough, otitis media and diarrhea.

Please see full prescribing information for Allegra Oral Suspension at http://products.sanofi-aventis.us/allegra_oral/allegra.pdf.

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 “expect,” “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.

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

About 700,000 People Each Year Seek Care In Emergency Departments For Adverse Supplement And Drug Reactions, Study Says

Adverse reactions to some of the most commonly prescribed medications result in more than 700,000 emergency department visits annually, according to a study published on Wednesday in the Journal of the American Medical Association, the AP/Washington Times reports. For the study, led by CDC epidemiologist Daniel Budnitz, researchers examined data from the first two years — 2004 to 2005 — of a national surveillance project on outpatient medication safety developed by CDC, FDA and the Consumer Product Safety Commission. The data included information from 63 nationally representative hospitals that reported 21,298 adverse reactions to medications among ED patients. According to the study, the data, when extrapolated nationwide, indicated that adverse reactions to medications accounted for at least 701,547 ED visits (Tanner, AP/Washington Times, 10/18). The study found that the most common adverse reactions among ED patients involved accidental overdoses and allergic reactions (Ricks, Long Island Newsday, 10/18). About 17% of ED patients who experienced adverse reactions to medications required hospitalization, the study found (AP/Washington Times, 10/18). In addition, the study found:

• The medications most commonly involved in adverse reactions among ED patients were insulins used to treat diabetes; pain medications that contain opiates, such as OxyContin; and blood thinners, such as Coumadin;

• The medications most commonly involved in allergic reactions among ED patients were antibiotics that contain amoxicillin and antihistamines and other over-the-counter cold treatments (McVicar, South Florida Sun-Sentinel, 10/18); and
• Patients ages 65 and older who experienced adverse reactions to medications were twice as likely to visit EDs and seven times as likely to require hospitalization as younger patients (AP/Washington Times, 10/18).

“These are estimates just of the patients who make it” to the ED, Budnitz said, adding, “We don’t even attempt to estimate the number of patients who never make it to treatment” (Long Island Newsday, 10/18).

An abstract of the study is available online.

CBS’ “Evening News” on Tuesday reported on the report. The segment includes comments from Paul Watkins, professor of medicine and pharmacotherapy at the University of North Carolina-Chapel Hill, and a U.S. patient who experienced an adverse reaction to a medication (LaPook, “Evening News,” CBS, 10/17).

The complete transcript of the segment is available online. The complete segment is available online in RealPlayer.

“Reprinted with permission from http://www.kaisernetwork.org. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at http://www.kaisernetwork.org/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork.org, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

FDA Approves Prescription Zaditor(R) For Over-The-Counter Relief From Itchy Eyes

Novartis Pharmaceuticals Corporation today announced that the U.S. Food and Drug Administration (FDA) has approved prescription Zaditor(R) (ketotifen fumarate ophthalmic solution 0.025%), indicated for the temporary prevention of itchy eyes due to allergic conjunctivitis, for OTC use. An estimated 40 million Americans suffer from eye allergies. Whether in reaction to seasonal allergens including pollen and ragweed, or perennial allergens such as animal hair or pet dander, itchy eyes are a main complaint.

While most OTC products provide only 3-4 hours of short-term relief, Zaditor’s full prescription strength formula offers eye itch relief that works in minutes and lasts up to 12 hours with just one drop. This significantly reduces the number of doses required per day to keep affected eyes itch-free. In addition, Zaditor is the first OTC eye itch medication safe for use in children as young as three.

“Now for the first time, people who suffer from itchy eyes caused by allergens such as pollen or pet dander can get fast, long-acting relief over- the-counter with Zaditor,” says Marion Morton, Head of the US Novartis Ophthalmics Business Unit. “Because Zaditor is now available at full prescription strength without a prescription, consumers can save time and money without sacrificing long-lasting symptom relief.”

Zaditor is the only OTC drop to treat eye itch associated with pollen, ragweed, grass, animal hair and dander without the potentially negative effects of a decongestant. Many OTC eye drops contain topical decongestants, which constrict the blood vessels to reduce the appearance of redness in the eye. With regular use, these products can interfere with the eye’s natural ability to regulate the blood vessels, resulting in a continued redness for a period of time after discontinuation (rebound effect). Zaditor does not contain a decongestant and may be used without risk of rebound redness.

“The availability of Zaditor without a prescription greatly improves treatment options for eye itch sufferers,” said Jane MacEnroe, MD, Associate Director, Medical Information and Communication, Novartis Ophthalmics. “For the first time, patients can get lasting relief over-the-counter without worrying about potential side-effects associated with long-term use of topical decongestants found in other OTC eye itch drops.”

Triple Mechanism of Action

Zaditor is the only OTC eye itch drop with a triple-action formula to provide fast, durable efficacy at the source. It includes a:

— Potent antihistamine that rapidly relieves itchy eyes within minutes

— Mast cell stabilizer that provides extended relief for up to 12 hours

— Prevents the release of chemical mediators to stop the late phase allergic reaction

Histamines, a chemical made by the body during an allergic reaction, are a primary cause of itchy eyes. Unlike most OTC drops, Zaditor blocks the histamines that cause itchy eyes and prevents the release of additional histamines, treating the source of the itch, not just the symptoms.

Approved in 1999 for prescription use, Zaditor has become a leading treatment for the temporary prevention of itchy eyes due to allergic conjunctivitis. Zaditor will be available over-the-counter in drug and chain stores nationwide beginning January 2007. It has a suggested retail price of $14.99 for a 30-day supply. In clinical studies, Zaditor was well tolerated and any side effects are generally mild.

About Novartis Ophthalmics

Novartis Ophthalmics, a business unit of Novartis Pharmaceuticals Corporation, is a leader in research, development and manufacturing of leading ophthalmic pharmaceuticals that assist in the treatment of age-related macular degeneration, eye inflammation, glaucoma, ocular allergies and other disorders of the eye. Novartis Ophthalmics products are available in more than 110 different countries. Novartis products are made in Switzerland, France, the United States and Canada.

About Novartis Pharmaceuticals Corporation

Located in East Hanover, New Jersey, Novartis Pharmaceuticals Corporation is an affiliate of Novartis AG (NYSE: NVS), a world leader in offering medicines to protect health, treat 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. Novartis is the only company with leadership positions in both patented and generic pharmaceuticals. 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. In 2005, the Group’s businesses achieved net sales of USD 32.2 billion and net income of USD 6.1 billion. Approximately USD 4.8 billion was invested in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 97,000 people and operate in over 140 countries around the world. For more information, please visit http://www.novartis.com/.

Disclaimer

The foregoing release contains forward-looking statements that can be identified by terminology such as “will,” or similar expressions, or by express or implied discussions regarding potential future sales of Zaditor. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results with Zaditor to be materially different from any future results, performance or achievements expressed or implied by such statements. Management’s expectations regarding Zaditor could be affected by, among other things, competition in general; increased government, industry, and general public pricing pressures; unexpected clinical trial results, including additional analysis of Zaditor clinical data, or new clinical data; unexpected regulatory actions or delays or government regulation generally; the company’s ability to obtain or maintain patent or other proprietary intellectual property protection; and other risks and factors referred to in the Company’s current Form 20-F on file with the U.S. 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.

Novartis Ophthalmics
http://www.novartis.com/

Allergy Drugs More Harmful Than Helpful For Chronic Ear Inflammation

Children who have persistent fluid in the middle ear, a condition called otitis media with effusion, are more likely to be harmed than helped by antihistamines and decongestants, a new review of studies has found.

The drugs are no better than placebo in alleviating symptoms or avoiding complications of OME and expose children to a significant risk of drug-related side effects.

“This review finds no benefit for any of the short- or long-term outcomes, including resolution of the fluid, hearing problems or the necessity of additional referral to specialists,” concluded review authors led by Glenn Griffin, M.D., of Quinte West Medical Centre in Ontario, Canada. “However, treated study subjects experienced 11 percent more side effects than untreated subjects.”

The review appears in the current issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates research in all aspects of health care. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing trials on a topic.

Otitis media with effusion is one of the most common conditions affecting young children, and about nine of 10 children will have OME at least once before school age. While OME usually is not painful, the presence of fluid in the middle ear can cause problems with hearing and balance.

Antihistamines and decongestants, commonly used to treat symptoms of allergies and colds, are sometimes prescribed for OME. According to the review authors, these drugs theoretically could alleviate congestion and decrease obstruction of the Eustachian tube, allowing drainage of fluid.

The reviewers pooled the results of 15 randomized controlled trials involving 1,516 children that compared antihistamines, decongestants or the combination to a placebo for otitis media with effusion.

The findings were consistently negative. Children who received decongestants alone or in combination with antihistamines were no more likely to be cured within one month than children who received a placebo. The same results were seen when children were evaluated at one to three months or after more than three months.

Likewise, for each of the other major outcomes the reviewers examined — hearing loss, risk of recurrent OME, development of acute otitis media and the need for surgery to drain fluid from the middle ear — the drugs performed no better than placebo. In fact, for hearing loss, there was a trend toward worse outcomes among the children who received medication.

In parallel with the consistent lack of benefit, the reviewers also found a significant risk of harm. In the six studies that evaluated side effects, 17 percent of children who received medication suffered side effects, compared with 6 percent of children who received a placebo.

The 11 percent difference in side effects means that for every nine children treated with these drugs, one would be harmed while none would benefit.

The results of this review came as no surprise to Richard Rosenfeld, M.D., director of pediatric otolaryngology at Long Island College Hospital in Brooklyn, N.Y. The real surprise, he said, is that physicians continue to prescribe these medications for a condition that in the vast majority of cases resolves on its own.

The 2004 American Academy of Pediatrics guideline for OME, for which Rosenfeld was co-chairman, recommended against the use of antihistamines and decongestants for OME based on the preponderance of harm over benefit. A 1994 guideline also found no data supporting the use of these drugs.

“There is absolutely no question that these products don’t work,” said Rosenfeld. “We have a very old, very consistent body of knowledge, all of which says the same thing, and yet these products are still commonly used by practicing clinicians.”

According to Rosenfeld, the continuing use of these drugs despite no evidence of benefit is a classic example of the way in which mental images can trump the best research.

“Parents will say, ‘My doctor gave me these medications to dry up the fluid,’ or, ‘If I use this, it’s going to open the Eustachian tube.’ Apparently that mental image is so powerful that it completely overwhelms common sense regarding the management of this disorder.”

The best-documented side effects of antihistamines and decongestants are insomnia, hyperactivity, drowsiness, behavioral changes and variability in blood pressure.

“These are pretty ubiquitous and nontrivial effects that can impair a child’s functioning at home and at school,” said Rosenfeld. “If you’re going to subject your child to any medication that has the potential for harm, there needs to be some assurance of benefit. Don’t use ineffective medications just because you have nice visual images. You’re better off doing nothing.”

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By Kelly Griffin, Contributing Writer Health Behavior News Service

Griffin GH, et al. Antihistamines and/or decongestants for otitis media with effusion (OME) in children. Cochrane Database of Systematic Reviews 2006, Issue 4.

The Cochrane Collaboration is an international nonprofit, independent organization that produces and disseminates systematic reviews of health care interventions and promotes the search for evidence in the form of clinical trials and other studies of interventions. Visit http://www.cochrane.org/ for more information.

Contact: Lisa Esposito
Center for the Advancement of Health

Potential New Therapeutic Target For Asthma, Allergies And Cancer

Virginia Commonwealth University researchers have identified how a bioactive molecule involved with allergy, inflammation and cancer is transported out of mast cells, according to findings published online this week in the Proceedings of the National Academy of Sciences.

Mast cells are specialized cells that react to allergy-causing agents by releasing substances that trigger the body’s allergic response, leading to conditions like asthma and hives. Among the molecules released by mast cells that participate in the allergic response is sphingosine-1-phosphate. This molecule is also implicated in cancer.

The work by the VCU investigators opens up a new approach to treating asthma, which affects about 15 million Americans and is increasing in incidence and mortality, especially among African-Americans. It also has implications for other allergic disorders and for cancer in terms of developing drugs that inhibit the transport of SIP out of cells.

Sarah Spiegel, Ph.D., professor and chair, VCU Department of Biochemistry, and colleagues reported how S1P, which also regulates many important physiological functions in cells, is transported out of mast cells. S1P is produced by all cells and secreted by some cells into the circulation where it can bind to specific S1P receptors. Until now, researchers have not known the mechanism by which S1P is transported out of cells.

“Our study shows that mast cells can use a special kind of transporter that has long been known to be used by cancer cells to push anti-cancer drugs out and help them survive the treatment,” said Spiegel. “Our study is the first to establish a mechanism by which S1P can be exported out of mast cells and perhaps by cancer cells as well.”

In previous research, Spiegel’s team found that S1P levels are significantly elevated in fluid collected from the lungs of asthmatic patients after exposure to an allergen. Those findings led Spiegel’s team to believe that mast cells could be a source of S1P. Mast cells are found in all body tissues and rapidly produce and secrete a number of inflammatory substances such as histamine and S1P when activated by an inflammatory stimulus. Spiegel said that S1P in turn amplifies allergic and inflammatory responses. Therefore, S1P secreted from mast cells can orchestrate many allergic responses, including asthma.

This work was supported by a grant from the National Institutes of Health.
The team included researchers Poulami Mitra, a Ph.D. candidate, Carole A. Oskeritzian, Ph.D., Shawn G. Payne, Ph.D., from the VCU Department of Biochemistry; Michael A. Beaven, Ph.D., a researcher with the National Heart, Lung, and Blood Institute; and Sheldon Milstien, Ph.D., a neuroscientist with the National Institute of Mental Health.

About VCU and the VCU Medical Center:
Located on two downtown campuses in Richmond, Va., Virginia Commonwealth University ranks among the top 100 universities in the country in sponsored research and enrolls 30,000 students in more than 180 certificate, undergraduate, graduate, professional and doctoral programs in the arts, sciences and humanities in 15 schools and one college. Sixty of the university’s programs are unique in Virginia, and 20 graduate and professional programs have been ranked by U.S. News & World Report as among the best of their kind. MCV Hospitals, clinics and the health sciences schools of Virginia Commonwealth University compose the VCU Medical Center, one of the leading academic medical centers in the country. For more, see http://www.vcu.edu/.

Contact: Sathya Achia-Abraham
Virginia Commonwealth University

Emergency Department Visits Necessary For Large Number Of Adverse Drug Events

Each year, an estimated 700,000 persons experience adverse drug events that lead to emergency department visits, according to a study in the October 18 issue of JAMA.

Outpatient use of drug therapies in the United States is common. In 2004, 82 percent of the U.S. population reported using at least 1 prescription medication, over-the-counter medication, or dietary supplement in the previous week and 30 percent reported using 5 or more of these drugs, according to background information in the article. While these medications may offer substantial benefits, there also may be risks. Information on outpatient adverse drug events (ADEs) has been difficult to collect, but the problem is large and can be expected to increase.

Daniel S. Budnitz, M.D., M.P.H., of the Centers for Disease Control and Prevention, Atlanta, and colleagues analyzed data from the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project (NEISS-CADES) to determine the frequency and characteristics of ADEs in the U.S. that have led to emergency department visits. The study included data from Jan. 2004 through Dec. 2005.

Over the 2-year study period, 21,298 adverse drug event cases were reported. “Based on data from a nationally representative surveillance system, we estimate that more than 700,000 patients were treated for ADEs in U.S. emergency departments annually in 2004 and 2005, and 1 of every 6 required subsequent hospital admission, transfer to another health care facility, or emergency department observation admission. Individuals aged 65 years or older were more than twice as likely to be treated in emergency departments for an ADE and nearly 7 times as likely to require hospitalization as individuals younger than 65 years. Among all patients who were hospitalized, most ADEs were due to unintentional overdoses and two-thirds of these were due to toxicity from a relatively small set of drugs for which regular monitoring is commonly required to prevent acute toxicity. Sixteen of the 18 drugs most commonly causing ADEs have been in clinical use for more than 20 years,” the authors write.

Adverse drug events accounted for 2.5 percent of estimated emergency department visits for all unintentional injuries and 6.7 percent of those leading to hospitalization, and also accounted for 0.6 percent of estimated emergency department visits for all causes.

Insulins or warfarin, drugs that typically require ongoing monitoring to prevent overdose or toxicity, were implicated in 1 in every 7 estimated ADEs treated in emergency departments.

“The finding that individuals aged 65 years or older (12 percent of the U.S. population) accounted for one-quarter of ADEs overall and half of adverse events requiring hospitalization highlights the importance of directing ADE prevention efforts to this vulnerable population. Emergency department visits for ADEs in this age group were nearly as common as those for motor vehicle occupant injuries,” the authors write.

“Efforts to reduce the burden of outpatient ADEs have been hampered by sparse data, except in selected health care systems or settings. Ongoing data collection in NEISS-CADES will enable more detailed examination of the epidemiology of emergency department-treated outpatient ADEs, focusing on specific patient populations, drug classes, conditions, and circumstances. Identifying appropriate measures of drug exposure and evaluating drug risks in relation to drug benefits remain important challenges in improving the quality of outpatient drug therapy,” the researchers write.

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(JAMA. 2006;296:1858-1866.)

Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Contact: Jennifer Morcone
JAMA and Archives Journals