# Zelnorm® to be made available to US patients under restricted access program



## Jeffrey Roberts (Apr 15, 1987)

Zelnorm® to be made available to US patients under restricted access program• FDA approves limited treatment IND program for Zelnorm• Novartis continues discussions with FDA to evaluate Zelnorm safety data and identify appropriate next steps East Hanover, NJ, July 27, 2007 - In cooperation with the US Food and Drug Administration (FDA), Novartis has established a restricted access program for Zelnorm® (tegaserod maleate) so that patients in need of this medicine can be considered for treatment.The program, called a treatment IND, is designed to help women in the US under 55 years of age who suffer from irritable bowel syndrome with constipation (IBS-C) or chronic idiopathic constipation (CIC), and for whom no other treatment has provided satisfactory relief and/or patients who had satisfactory improvement of their symptoms with prior Zelnorm treatment for IBS-C or CIC. Novartis and the FDA are moving forward with this program because of requests from physicians and patients following the marketing suspension of Zelnorm in March 2007.Treatment INDs are generally used to allow restricted access to medications for patients in need if no comparable alternative drug or therapy is available to treat the disease. Patients given access through a treatment IND must meet specific FDA-approved criteria for enrollment.Through the program, appropriate female patients with IBS-C or CIC who are assessed by their physicians as being in critical need can have access to Zelnorm for relief of the often painful and disruptive symptoms associated with these conditions. The program protocol and consent materials are designed to ensure that patients and physicians are fully informed of the potential risks and benefits of Zelnorm.To be considered for access to Zelnorm through the treatment IND, patients must have IBS-C or CIC and meet the specific criteria in the treatment IND protocol. To become part of the treatment IND, patients should contact their physicians to inquire about the protocol and evaluate if they meet the criteria. For further details of the program's protocol, physicians can call 866-248-1348 or 888-669-6682 or go to www.zelnorm.com.For patients who do not meet the criteria of the treatment IND but have an urgent need for Zelnorm based on a life-threatening or severely debilitating condition, there may be an alternative option available through the FDA. Physicians may inquire about this potential access option by contacting Novartis at (888-NOW-NOVA) or the FDA CDER Division of Drug Information at 301-827-4570 or www.fda.gov/cder.Novartis suspended US marketing and sales of Zelnorm as a result of an FDA request in order to permit further discussion of its benefit/risk profile. This decision was based on a review of a new retrospective analysis of pooled clinical trial data which showed that the incidence of cardiovascular ischemic events was higher in patients taking Zelnorm than in those taking placebo. However, no causal relationship between Zelnorm and cardiovascular ischemic events has been demonstrated.Novartis has extensively studied Zelnorm and believes that this medicine provides important benefits for appropriate patients. Novartis is in discussions with the FDA to better understand the findings and to determine appropriate next steps.IBS is a disorder characterized by abdominal pain or discomfort, bloating, and altered bowel function. An estimated 12 million Americans suffer from IBS with constipation. Many have symptoms for five to 10 years, which trigger missed work days and often prevent them from participating in everyday activities with their family and friends. Chronic constipation accounts for more than 5.7 million constipation-related outpatient visits each year, with more than 990,000 visits to emergency rooms and more than 580,000 to hospital outpatient facilities. It leads to more than 282,000 in-patient hospitalizations with constipation as the primary diagnosis.DisclaimerThe foregoing press release contains forward-looking statements that can be identified by the use of forward-looking terminology such as "to be," "continues," "can have," "may," "believes" or by express or implied discussions regarding potential future regulatory filings, approvals or future sales of Zelnorm. Such forward-looking statements reflect the current views of Novartis regarding future events and involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that any future regulatory filings will satisfy regulatory requirements regarding Zelnorm, that Zelnorm will be brought back to market in the the US or any additional market or that Zelnorm will reach any particular level of sales. In particular, management's expectations regarding Zelnorm could be affected by, among other things, unexpected regulatory actions or delays or government regulation generally; unexpected clinical trial results, including additional analysis of clinical data, or unexpected new clinical data, as well as the additional risks and factors discussed in Novartis AG's Form 20-F filed with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those described herein as anticipated, believed, estimated or expected. Novartis is providing this information as of this date and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise.About NovartisNovartis Pharmaceuticals Corporation researches, develops, manufactures and markets leading innovative prescription drugs used to treat a number of diseases and conditions, including those in the cardiovascular, metabolic, cancer, organ transplantation, central nervous system, dermatological, gastrointestinal and respiratory areas. The company's mission is to improve people's lives by pioneering novel healthcare solutions.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, cure disease and improve well-being. Our goal is to discover, develop and successfully market innovative products to treat patients, ease suffering and enhance the quality of life. We are strengthening our medicine-based portfolio, which is focused on strategic growth platforms in innovation-driven pharmaceuticals, high-quality and low-cost generics, human vaccines and leading self-medication OTC brands. Novartis is the only company with leadership positions in these areas. In 2006, the Group's businesses achieved net sales of USD 37.0 billion and net income of USD 7.2 billion. Approximately USD 5.4 billion was invested in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 100,000 associates and operate in over 140 countries around the world. For more information, please visit http://www.pharma.us.novartis.com.# # #Novartis Media ContactsAnna FrableNovartis Pharmaceuticals Corporation862-778-5388 (Office)732-673-5262 (Cell)[email protected] SutherlandNovartis Pharmaceuticals Corporation862-778-0323 (Office)917-330-5981 (Cell)[email protected]


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## Jeffrey Roberts (Apr 15, 1987)

July 27, 2007 Media Inquiries: Rita Chappelle, 301-827-6242Consumer Inquiries: 888-INFO-FDA *FDA Permits Restricted Use of Zelnorm for Qualifying Patients*The U.S. Food and Drug Administration announced that it is permitting the restricted use of Zelnorm (tegaserod maleate) under a treatment investigational new drug (IND) protocol to treat irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC) in women younger than 55 who meet specific guidelines.In some instances, patients with a serious or life-threatening disease or condition who are not enrolled in a clinical trial may be treated with a drug not approved by the FDA. Generally, such use is allowed within guidelines called a treatment IND, when no comparable or satisfactory alternative drug or therapy is available.In addition to the age and gender restrictions, the IND protocol for Zelnorm limits use of the drug to those with IBS-C or CIC whose physicians decide the drug is medically necessary. Patients must sign consent materials to ensure they are fully informed of the potential risks and benefits of Zelnorm. On March 30, 2007, the FDA asked Novartis, the manufacturer of Zelnorm, to suspend its U.S. marketing and sales because a safety analysis found a higher chance of heart attack, stroke, and unstable angina (heart/chest pain) in patients treated with Zelnorm compared with treatment with an inactive substance (placebo). At that time, the FDA indicated that there might be patients for whom the benefits of Zelnorm treatment outweigh the risks and for whom no other treatment options were available. FDA committed to work with Novartis to allow access to Zelnorm for those patients through a special program. That work yielded this IND protocol."These patients must meet strict criteria and have no known or pre-existing heart problems and be in critical need of this drug," said Steven Galson, M.D., M.P.H., director of FDA's Center for Drug Evaluation and Research (CDER). "Zelnorm will remain off the market for general use."Irritable bowel syndrome is a disorder characterized most commonly by cramping, abdominal pain, bloating, constipation, and diarrhea. IBS causes a great deal of discomfort and distress, but it does not permanently harm the intestines and does not lead to disease. For some people, however, IBS can be disabling. They may be unable to work, attend social events, or even travel short distances.Patients are considered to have chronic constipation if they have fewer than three complete spontaneous bowel movements per week and at least one of the following symptoms for at least 25 percent of those bowel movements: straining, hard stools, incomplete evacuation. Physicians with IBS-C or CIC patients who meet the IND criteria should contact Novartis at 888- 669-6682 or 866-248-1348. Those who do not qualify for the Zelnorm treatment protocol may contact FDA's Division for Drug Information about other options at 888-463-6332. For more information: Novartis Zelnorm Web pagewww.zelnorm.comNational Institute of Diabetes and Digestive and Kidney Diseases-Irritable Bowel Syndromehttp://digestive.niddk.nih.gov/ddiseases/pubs/ibs/International Foundation for Functional Gastrointestinal Disorderswww.iffgd.orgFDA Center for Drug Evaluation and Researchwww.fda.gov/cder ####


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## Jeffrey Roberts (Apr 15, 1987)

Frequently Asked Questions About The Treatment IND?*What is the Zelnorm treatment IND program?* This program, called a "treatment IND," allows restricted access to Zelnorm if there is no comparable alternative drug or therapy available to treat the disease in the intended patient population. Under the Zelnorm treatment IND program, female patients with IBS-C or CIC will be considered to receive the medication if they meet the FDA approved criteria. *Who will qualify for the Zelnorm treatment IND program?* To be considered for access to Zelnorm through the treatment IND, female patients under 55 with IBS-C or CIC must meet the specific criteria outlined in the treatment IND protocol approved by the FDA. *What about patients who do not qualify for the Zelnorm treatment IND?* There may be an alternative access option available through the FDA for patients who do not meet the criteria of the treatment IND but have an urgent need for Zelnorm based on a life-threatening or severely debilitating condition. Physicians may inquire about this potential access option by contacting the FDA CDER Division of Drug Information at 301-827-4570 or www.fda.gov/cder. *How do patients/physicians enroll in the treatment IND program?* Female IBS-C or CIC patients under 55 seeking to enroll should contact their physicians to inquire about the protocol and evaluate if they meet the FDA-approved criteria. For further details of the program's protocol, physicians can call 866-248-1348 or 888-669-6682. *What is the cost of Zelnorm through this treatment IND?* If a patient is approved for the Zelnorm treatment IND , Novartis will provide Zelnorm at no cost to the patient. *How much medication will a patient receive?* If approved to participate in the treatment IND, Novartis will provide each patient with one month's supply of 6mg Zelnorm. Reauthorization from the physician will be required for an additional supply of Zelnorm to be sent to the patient. *How long will the treatment IND be available?* The treatment IND program is available now for patients with IBS-C or CIC who meet the approved inclusion/exclusion criteria. As Novartis is continuing to work with the FDA on the safety and benefit assessment of Zelnorm, we can not speculate at this time how long this new treatment IND program will be open. *Should patients take Zelnorm under the treatment IND program given the reported cardiovascular events?* This program was established in response to requests to Novartis and the FDA from patients and physicians following the marketing suspension earlier in the year. The program materials are designed to help ensure that physicians are fully informed of the potential risks and benefits of Zelnorm, and can make appropriate medical judgments about whether the drug makes sense for their individual patients. Patients will also receive materials about the potential risks and benefits, to allow them to make an informed consent to participate. In addition, the treatment IND will not include patients who have cardiovascular ischemic disease or cardiovascular risk factors. *What are the Zelnorm treatment IND inclusion criteria?*Key inclusion criteria include: 
Women under the age of 55 years
Currently suffering with IBS-C or Chronic Idiopathic Constipation
No satisfactory response to other available treatments and/or patients who had satisfactory improvement of their symptoms with prior Tegaserod treatment
 Key exclusion criteria include: 
History or current diagnosis of cardiovascular ischemic disease
Symptoms suggestive of cardiovascular ischemic disease
Presence of any cardiovascular risk factors according to NIH guidelines
Uncompensated depression or anxiety or suicidal ideation or behavior
 To become part of this program, patients should contact their physicians to inquire about the protocol and evaluate if they meet the criteria.From http://www.zelnorm.com retrieved on July 27, 2007


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## Jeffrey Roberts (Apr 15, 1987)

Some further notes about the IND protocol:The IND protocol provides 70 - 6 mg. tablets monthly to patients via their physicians at NO CHARGE. A re-assessment by your physician must take place at the end of each month to determine whether the benefits continue to outweigh the risks. Patients must undergo a new ECG and Lipid profile before initially receiving access. Historical data will not suffice, ie: an ECG or Lipid profile 3 months ago is not good enough. These tests are done at the patients own expense. Inclusion for access to the IND protocol - per Rome Criteria for IBS-C and CC- no satisfactory relief from other treatments or previous success with Zelnorm- under 55 years old [Side note about 55 years old - following NIH guidelines for cardiovascular disease. Risks increase greatly 55 and above. Patients 55 years or older must use Emergency IND for access. This IND protocol will not cover them.] Exclusion for access to the IND protocol - symptoms or known cardio or family history factors- refer to NIH cardio guidelines Logistics Physician calls Quntiles, 888- 669-6682 or 866-248-1348, to confirm interest. Qunitiles sends an enrollment kit, training materials and FDA regularity forms which checks basic physician qualifications and confirms that physician is not blacklisted by FDA. Novartis sends medication directly to physician at NO CHARGE. It is a very simple process.


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## Tiss (Aug 22, 2000)

Jeff, do you know how long it takes to go through this process to actually get the Zelnorm in the patient's hands?


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## Jeffrey Roberts (Apr 15, 1987)

Tiss,From my understanding it really depends on the length of time it takes to get an appointment with your physician, have the physician make the request for the kit, get regulatory approval, send you for a new ECG and Lipid profile, get those results, and then order the medication. It everything lines up it seems like it could be rather quick; however, you are more or less dependent on your physician to move this forward. Once the medication is sent from Quintiles it is only dependent on the speed of the mail.Jeff


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