# Zelnorm Study Shows Significant Improvement in Work Productivity



## Jeffrey Roberts (Apr 15, 1987)

Second study finds reduction in healthcare resource utilization in women with IBS ORLANDO, Fla., Nov. 3 /PRNewswire/ -- A new health economic study forZelnorm® (tegaserod maleate) shows a significant improvement in overall workproductivity in employed women who suffer with Irritable Bowel Syndrome (IBS)with constipation. The data demonstrated that women receiving Zelnorm showed a decrease inabsenteeism (missed time at work) and presenteeism (reduced on-the-jobeffectiveness). On average, patients receiving Zelnorm were able to worktwo-and-one-half hours more per week compared to patients receiving placebo. The productivity results -- assessed as part of a randomized,double-blind, placebo-controlled, multi-center clinical trial of Zelnormcompared to placebo in 2,650 women -- were presented today during the 69thannual meeting of the American College of Gastroenterology (ACG). Positiveresults were seen in work productivity early on and those benefits weremaintained until the end of the four-week trial period with the pro-motilityagent, Zelnorm. "It is exciting to see an intervention produce clinical benefit and alsodemonstrate a significant improvement in patients' ability to work and conductdaily activities," says Margaret Reilly, who conducted the study and is ahealth economic analyst and president of Margaret Reilly Associates, Inc., NewYork. "Data of this type helps patients, employers, physicians, the medicalcommunity, and insurers because it begins to quantify the contribution atherapy can make on a personal and health economic level." For employed patients with IBS, direct medical and indirect productivitycosts to the employer have been estimated to be 50 percent higher than foremployees without IBS(1). It is estimated in the United States alone that theannual costs of IBS are $30 billion, with indirect costs, including lost daysat work, estimated at $20 billion(1),(2),(3). These costs do not includepartial day absences, or reduced on-the-job effectiveness. The productivity results at the end of four weeks found Zelnormsignificantly reduced absenteeism by 2.6 percent (p .LE. 0.004), presenteeism by5.4 percent (p .LE. 0.0001), overall work productivity loss by 6.3 percent(p .LE. 0.0001), and daily activity impairment by 5.8 percent (p .LE. 0.0001).The health economic endpoints were assessed by the validated Work Productivityand Activity Impairment Questionnaire for IBS (WPAI-IBS); the validation ofwhich was published in August 2004 in Alimentary Pharmacology andTherapeutics(4). The WPAI measures absenteeism, presenteeism, and impairmentwith daily activities in the past seven days. Daily activities included butwere not limited to housework, shopping, childcare, exercising and studying. The clinical trial included a two-week baseline period followed by afour-week placebo-controlled treatment period. Women in the trial met theaccepted diagnostic (Rome II) criteria for IBS with constipation. Those inthe Zelnorm arm took 6 mg of Zelnorm twice a day. Of the 1,675 employed studypatients, the mean age was 40.8 years and the mean duration of IBS symptomswas 13 years. In the Zelnorm group, 63.8 percent were employed compared to59.4 percent in the placebo group. Prior to study enrollment, patientsreported absenteeism (51 percent), presenteeism (92 percent), and limitationsin daily activities due to IBS with constipation (87 percent). "We know that recurring constipation, abdominal pain and bloatingassociated with IBS with constipation can significantly reduce a person'squality of life," says Alex Gorsky, chief operating officer of NovartisPharmaceuticals Corporation. "It is gratifying for us to learn that treatmentwith Zelnorm can help patients feel good enough to be more productive atwork." Zelnorm Significantly Reduced Healthcare Resource Utilization in ManagedCare for Patients with IBS with Constipation A second study presented at ACG of 3,365 new Zelnorm users and 3,364matched non-Zelnorm users carried out by a large geographically diversemanaged care organization found that effective treatment with Zelnorm reducedthe use of GI-related medical healthcare resources that included physicianoffice visits, emergency room (ER) visits, hospitalizations and diagnosticprocedures. The study found that during the six-month study period, all GI-relatedmedical resource categories showed significant (p .LT. 0.01) absolute decreases inutilization, with a relative decrease between 20 and 40 percent for Zelnormusers that was not observed consistently for non-Zelnorm users. GI drug usedid not change significantly for Zelnorm users; however, there was astatistically significant, 15 percent relative increase, (p .LT. 0.01) fornon-Zelnorm users. Zelnorm reduced the number of GI-related physician office visits by 22percent (-0.42 visits), hospitalizations by 33 percent (-0.02hospitalizations), ER visits by 40 percent (-0.04 visits), endoscopicprocedures by 21 percent (-0.08 procedures), and non-endoscopic procedures by31 percent (-0.16 procedures), when compared to the use of these resourcesduring the six months prior to taking Zelnorm for IBS or a GI-relateddisorder. Eighty-two percent of Zelnorm users had diagnostic claims consistentwith IBS, or one or more of the cardinal symptoms of IBS: IBS (48 percent),abdominal pain (40 percent), bloating (11 percent), or constipation (38percent) during the study period. This retrospective, longitudinal study used medical and pharmacy claimsusing ICD-9-CM codes to identify Zelnorm users and matched non-Zelnorm userswho were continuously enrolled, benefit-eligible patients. GI-relatedresource use was compared for the six months prior to and following use ofZelnorm. In comparing post utilization to pre utilization, all GI-relatedmedical resource categories showed a significant decrease (p .LT. 0.01) for Zelnormusers that was not seen consistently in the control group. About Zelnorm As a pro-motility agent, Zelnorm acts as an agonist at 5HT4 (serotonintype 4) receptors in the GI tract and mimics the natural effects of serotoninby activating 5HT4 receptors, which normalizes impaired motility in the GItract, inhibits visceral sensitivity and stimulates intestinal secretion.Zelnorm treats dysmotility symptoms caused by chronic constipation and IBSwith constipation. Zelnorm is indicated for the short-term treatment of women with IBS whoseprimary bowel symptom is constipation. The safety and effectiveness of Zelnormin men with IBS with constipation have not been established. Zelnorm also isindicated for the treatment of patients less than 65 years of age with chronicidiopathic constipation, a condition that affects up to 4.5 million Americans.Effectiveness of Zelnorm in patients 65 years or older with this condition hasnot been established. Zelnorm was developed by Novartis and is also known in some countries asZelmac. It is approved in more than 55 countries for IBS with constipation.Zelnorm also is approved for use in chronic constipation in 10 countries,including Mexico and Latin America. Zelnorm is being studied as a potentialtreatment for other important GI motility disorders, includinggastroesophageal reflux disease (GERD) and dyspepsia. Zelnorm Safety Data Overall, safety data is now available in more than 11,600 patients whohave enrolled in clinical trials assessing Zelnorm's safety and efficacy invarious GI conditions. In IBS with constipation clinical trials, Zelnorm was generally welltolerated. The only adverse event reported notably more often with Zelnormthan with placebo was diarrhea (9 percent vs. 4 percent). The majority ofpatients reporting diarrhea had a single episode and in most cases, diarrheaoccurred in the first week of treatment. Typically, it resolved withcontinued therapy. Serious consequences of diarrhea, including hypovolemia,hypotension and syncope, have been reported in the clinical studies(0.04 percent) and during marketed use of Zelnorm. In some cases, thesecomplications have required hospitalization for rehydration. In chronic constipation studies, the only adverse event reported moreoften with Zelnorm 6 mg twice a day than placebo was diarrhea (6.6 percent vs.3 percent). Diarrhea rarely led to discontinuation of the study (0.9 percent).Typically, diarrhea was transient, lasting two days, and generally resolvedwithout rescue medication or interruption of treatment. Data from the trialthat incorporated a 13-month extension study showed Zelnorm to be generallysafe and well tolerated long term. This release contains certain forward-looking statements relating to theCompany's business, which can be identified by the use of forward-lookingterminology such as "can make," "can help," "potential treatment," or similarexpressions, or by express or implied discussions regarding potential newapprovals or new indications or future sales of Zelnorm. Such forward-lookingstatements reflect the current views of the Company with respect to futureevents and are subject to certain risks, uncertainties and assumptions. Therecan be no guarantee regarding potential future revenues from Zelnorm or thatZelnorm will be approved for any additional indications or in any additionalcountries. In particular, management's expectations could be affected, amongother things, by uncertainties relating to unexpected regulatory actions ordelays; government regulation generally; new clinical data; unexpectedclinical trial results; the ability to obtain or maintain patent or otherproprietary intellectual property protection; competition in general;government, industry, and general public pricing pressures; and other risksand factors referred to in the Company's current Form 20-F on file with theSecurities and Exchange Commission of the United States. Should one or moreof these risks or uncertainties materialize, or should underlying assumptionsprove incorrect, actual results may vary materially from those describedherein as anticipated, believed, estimated or expected. Novartis is providingthe information in this news release as of this date and does not undertakeany obligation to update any forward-looking statements contained in this newsrelease as a result of new information, future events or otherwise. About Novartis Novartis Pharmaceuticals Corporation researches, develops, manufacturersand markets leading innovative prescription drugs used to treat a number ofdiseases and conditions, including central nervous system disorders, organtransplantation, cardiovascular diseases, dermatological diseases, respiratorydisorders, cancer and arthritis. The company's mission is to improve people'slives by pioneering novel healthcare solutions. Located in East Hanover, New Jersey, Novartis Pharmaceuticals Corporationis an affiliate of Novartis AG (NYSE: NVS), a world leader in pharmaceuticalsand consumer health. In 2003, the Novartis Group's businesses achieved salesof USD 24.9 billion and a net income of USD 5.0 billion. The Group investedapproximately USD 3.8 billion in R&D. Headquartered in Basel, Switzerland,Novartis Group companies employ about 78,500 people and operate in over 140countries around the world. For further information please consult http://www.novartis.com. For more information and for a copy of the complete prescribinginformation, please contact: Carrie Callahan (862) 778-7065, or via email atcarrie.callahan###pharma.novartis.com. References 1. Leong SA, Barghout V, Birnbaum HG, et al. The economic consequences of irritable bowel syndrome: a US employer perspective. Arch Intern Med 2003; 163: 929-35. 2. Martin R, Barron JJ, Zacker C. Irritable bowel syndrome: toward a cost-effective management approach. Am J Manage Care 2001; 7(Suppl. 8): S268-75. 3. American Gastroenterological Association. The burden of gastrointestinal diseases, 2001. 4. Reilly MC, et al. The validity and accuracy of the work productivity and activity impairment questionnaire- irritable bowel syndrome version. Aliment Pharmacol Ther 2004; 20: 1-9. Contacts Carrie Callahan Novartis Pharmaceuticals Corporation Tel 862 778 7065 (direct) or 917 348 9437 (mobile) carrie.callahan###pharma.novartis.com John Gilardi Novartis Global Media Relations Tel +41 61 324 30 18 (direct) or +41 79 593 42 91 (mobile) john.gilardi###group.novartis.com Kevin Bannon Ruder Finn Public Relations Tel 212 715 1621 (direct) or 917 679 9126 (mobile) bannonk###ruderfinn.comSOURCE Novartis Pharmaceuticals CorporationWeb Site: http://www.novartis.com


----------

