Novartis suspends US marketing and sales of Zelnorm

[JohnMack]

Source: Novartis Press Release

Novartis suspends US marketing and sales of Zelnorm(R) in response to request from FDA


# Retrospective analysis of pooled clinical trial data shows numerical imbalance in cardiovascular events in patients taking Zelnorm compared to those on placebo

# FDA asks Novartis to suspend marketing and sales to permit further discussion of benefits and risks of Zelnorm

# Novartis believes Zelnorm provides important benefits for appropriate patients suffering from irritable bowel syndrome with constipation

# Discussions ongoing with FDA to evaluate best way to continue to make Zelnorm available to appropriate US patients

Basel, March 30, 2007 - Novartis is complying with a request from the Food and Drug Administration (FDA) to suspend US marketing and sales of Zelnorm®[*] (tegaserod maleate), a treatment for irritable bowel syndrome (IBS) with constipation and chronic constipation.

This action has been taken after Novartis notified the FDA about a retrospective analysis of data from more than 18,000 patients in the clinical trial database. This was the result of an ongoing review involving a number of health authorities including the FDA.

A small (but not statistically significant) imbalance in cases of angina pectoris was recorded and included in the US label when Zelnorm was approved in 2002. A recent analysis of the entire clinical database revealed a statistically significant imbalance in the incidence of cardiovascular ischemic events in patients taking Zelnorm/Zelmac compared to those taking placebo. These events included myocardial infarction, stroke, and unstable angina pectoris.

The data, which were reviewed by independent experts, showed that events occurred in 13 out of 11,614 patients treated with Zelnorm/Zelmac (0.11%), compared to one case in 7,031 placebo-treated patients (0.01%). All patients affected had pre-existing cardiovascular disease and/or CV risk factors.

The rate of cardiovascular ischemic events seen in Zelnorm/Zelmac-treated patients in controlled trials corresponds approximately with the expected rates for such events in the general population.


"My review of the data suggested that a causal relationship is unlikely between tegaserod and the rare cardiovascular ischemic events observed in clinical trials," said Jeffrey L. Anderson, MD, Professor of Internal Medicine at the University of Utah and Associate Chief, Cardiology Division, LDS Hospital in Salt Lake City and an independent cardiologist who reviewed the data. "Furthermore, the data did not show any consistent pattern of event type, time to event or dose relationship in tegaserod-treated patients."

Multiple studies do not suggest any constrictive effects of Zelnorm on coronary arteries.

An estimated 12 million Americans suffer from the painful and disruptive symptoms of 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.

"Zelnorm/Zelmac provides unique benefits to patients by treating the multiple symptoms of abdominal pain, bloating and constipation that are associated with IBS with constipation," said James Shannon, MD, Global Head of Development at Novartis Pharma AG. "Although we have complied with the FDA's request and are collaborating with the agency, we continue to believe that Zelnorm/Zelmac provides important benefits for appropriate patients."

Nevertheless, Novartis has suspended the marketing, sales and distribution of Zelnorm in response to the FDA's request, so that public discussion and an Advisory Committee meeting can take place to determine the risks and benefits of this medicine.

Novartis and the FDA will communicate this information to physicians and patients, and will discuss the best way to continue to make Zelnorm available to appropriate patients, including through a Treatment IND. US patients taking Zelnorm are being advised to consult their physicians.

Novartis is in discussion with health authorities in other countries where Zelnorm/Zelmac is available to determine next steps. Patients outside the US who have any concerns about Zelnorm/Zelmac should discuss the situation with their healthcare professional.

About Zelnorm
Zelnorm received FDA approval for the short-term treatment of women with IBS in the US on July 24, 2002. Zelnorm also received FDA approval for the treatment of men and women less than 65 years of age with chronic idiopathic constipation in the US on August 20, 2004.

Zelnorm/Zelmac is approved for the treatment of IBS with constipation in 50 countries including Australia, Switzerland, Canada, the US, Mexico, China and Brazil. Zelnorm/Zelmac is also approved for the treatment of chronic constipation in more than 20 countries including the US, Canada and Mexico. Novartis markets the therapy under the trademark Zelnorm (tegaserod maleate) in the US, Canada, Philippines and South Africa; and as Zelmac (tegaserod) in Switzerland, Latin America and the Asia-Pacific region.

Financial update
For its 2007 financial guidance, Novartis has revised its outlook for net sales growth, barring unforeseen events, for the Group to above five percent, and for the Pharmaceuticals division to a low- to mid-single-digit rate, both in local currencies.

Novartis is still evaluating the impact on the full-year 2007 operating and net income results from continuing operations (excluding the announced divestiture of Medical Nutrition expected to be completed in 2007).

An invitation will be issued to financial analysts to join an update telephone conference call at 19:00 Central European Summer Time (CEST) on Friday, March 30. A listen-only version of this event will be available on the Internet at www.novartis.com, where a recorded version of this conference call will be made available after the event.

Disclaimer
The foregoing release contains certain forward-looking statements that can be identified by terminology such as "will," "outlook," or similar expressions, or by express or implied discussions regarding potential future approvals to return Zelnorm/Zelmac to the market, or potential future sales of Zelnorm/Zelmac, or the potential impact of Zelnorm/Zelmac on the potential future sales or earnings of the Novartis Group or its Pharmaceuticals Division. Such forward-looking statements involve known and unknown risks, uncertainties or other factors that may cause the 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 Zelnorm/Zelmac will be approved by the FDA or other health authorities for return to the market for any indication, or that Zelnorm/Zelmac will achieve any particular level of sales. Nor can there be any guarantees that the Novartis Group, or the Pharmaceuticals Division, will achieve any particular financial results. In particular, management's expectations regarding these matters could be affected by, among other things, unexpected regulatory actions or delays or government regulation generally; unexpected clinical trial results or results of data analysis, including additional analysis of existing clinical data and other data regarding patients' experience with Zelnorm/Zelmac, or unexpected new clinical or other such data; competition in general; government, industry and general public pricing pressures; the ability to obtain or maintain patent or other proprietary intellectual property protection; as well as factors discussed in the Company's Form 20-F filed with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

About Novartis
Novartis AG (NYSE: NVS) is a world leader in offering medicines to protect health, cure disease and improve well-being. Our goal is to discover, develop and successfully market innovative products to treat patients, ease suffering and enhance the quality of life. We are strengthening our medicine-based portfolio, which is focused on strategic growth platforms in innovation-driven pharmaceuticals, high-quality and low-cost generics, human vaccines and leading self-medication OTC brands. Novartis is the only company with leadership positions in these areas. In 2006, the Group's businesses achieved net sales of USD 37.0 billion and net income of USD 7.2 billion. Approximately USD 5.4 billion was invested in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 101,000 associates and operate in over 140 countries around the world. For more information, please visit http://www.novartis.com.

# # #

Novartis Media Relations

John Gilardi
Novartis Global Media Relations
+41 61 324 3018 (direct)
+41 79 596 1408 (mobile)
john.gilardi@novartis.com

[JohnMack]

Source: Bloomberg

Novartis Stops Zelnorm Marketing, Sales on Heart Risk (Update4)

By Eva von Schaper

March 30 (Bloomberg) -- Novartis AG, Switzerland's largest drugmaker, stopped U.S. sales of its Zelnorm irritable bowel syndrome treatment at the request of the Food and Drug Administration after people taking the medicine had more heart attacks and strokes.

A review of data from 18,000 patients showed that a statistically significant number had heart problems, and one patient died. The heart attack rate ``corresponds approximately with the expected rates for such events in the general population,'' Basel, Switzerland-based Novartis said today.

Zelnorm was approved in 2002 for irritable bowel syndrome and constipation, and brought in $561 million in last year. The FDA asked Novartis to stop sales, and the agency said it would consider a ``limited re-introduction'' if benefits are proven in new tests. Novartis lowered its full-year sales forecasts.

``This is a serious blow,'' Denise Anderson, an analyst with Kepler Lansbanki in Zurich said in a telephone interview today. ``This was a drug that had a delay in the approval, a slow build in sales and we thought it was finally coming into its own.'' Anderson estimated the drug would eventually bring in more than $1 billion a year.

Novartis American depositary receipts fell $1.98, or 3.4 percent, to $54.98 in New York Stock Exchange trading at 2:10 p.m. The Swiss shares rose 45 centimes, or 0.7 percent, to 69.70 Swiss francs ($57.48) today.

Novartis now says net sales will rise more than 5 percent for the whole company and to low- to mid-single digit rate for the drug division. Novartis had forecast mid- to high-single digit sales rate for the entire company and mid-single digit sales growth in the pharmaceuticals unit.

EU Rejection

Zelnorm brought in $488 million in the U.S. in 2006, where about 500,000 people are taking the product. Sales are suspended in Canada, and Novartis is talking to health agencies in other countries. The drug will stay on the market in Switzerland.

``I don't know'' if the medicine will return, Novartis Chief Executive Officer Daniel Vasella said on a conference call. The product could have stayed on the market with a label change, he said. The patients taking sugar pills in the tests had an unexpectedly low rate of heart attacks, Vasella said.

Last year, the medicine was rejected for a second time by a European Union health advisory panel. The risks of Zelnorm outweighed the possible benefits, the European Medicines Agency committee said last March. Novartis applied to use Zelnorm for women with constipation, and appealed the rejection.

The EMEA was concerned that taking the drug ``would not translate into real benefit to the patient treated,'' the panel said at the time. ``Zelnorm's benefits are not greater than its risks.''

Other Suspensions

Regulators are becoming tougher after the recall of Merck & Co.'s Vioxx painkiller because of links to heart attacks and strokes. Last year, the FDA allowed Elan Corp. and Biogen Idec Inc.'s Tysabri multiple sclerosis medicine back on the market after the product was linked to a fatal side effect.

Yesterday the FDA said Permax, a drug for Parkinson's disease, is being withdrawn in the U.S. after two studies linked the product to heart valve damage, regulators said.

Tysabri was only the second drug to be put back on the U.S. market following a safety-related suspension. The only other was GlaxoSmithKline Plc's irritable bowel drug Lotronex, returned to the market with restrictions in 2002 after a link to patient deaths.

While the overall number of Zelnorm patients who suffered a heart attack, stroke or severe chest pain that can turn into a heart attack, one tenth of a percent, the percentage of patients taking Zelnorm that had serious and life-threatening side effects was ten times higher that the percentage of patients taking a sugar pill.

`No Longer Favorable'

``We believe that the risk versus benefit profile of Zelnorm is no longer favorable,'' John Jenkins, director of the FDA's office of new drugs, said in a conference call today. Novartis agreed with the FDA's assessment yesterday after meeting with regulators to discuss their concerns.

People taking the medicine should speak to their doctors to discuss other possible treatments, the FDA said.

Zelnorm was approved for short-term treatment of women with irritable bowel syndrome with constipation and for patients younger than 65 years with chronic constipation.

In late February and early March, Novartis gave the FDA results of new analyses of 29 clinical studies of Zelnorm for treatment of a variety of gastrointestinal tract conditions. The data from all the studies were combined to assess the chance of side effects on the heart and blood vessels.

The 29 studies included 11,614 patients treated with Zelnorm and 7,031 treated with a sugar pill, the agency said. The average age was 43 years and 88 percent of patients were women.

One Death

Thirteen patients treated with Zelnorm had serious side effects, including four heart attacks and three strokes. One person died. Only one patient taking the sugar pill had symptoms suggesting the beginning of a stroke, which went away without complication.

``It really took pulling together all 29 studies that have been conducted throughout the entire life of the product to see this level of a signal,'' Jenkins said.

Zelnorm may be the only treatment option for some patients with severe symptoms of irritable bowel syndrome, Jenkins said.

``We have to wait and see how many patients feel like they were really gathering significant benefit from Zelnorm and whose symptoms were so severe that they'd consider continuing to take the drug,'' Jenkins said. ``It's really heart to know how many patients would want to continue.''

It will take ``at least several weeks'' before a program to start a new trial for the drug is in place, Jenkins said.

To contact the reporter on this story: Eva von Schaper in Munich at evonschaper@bloomberg.net .

[JohnMack]

Source: FDA

Tegaserod maleate (marketed as Zelnorm)

FDA is issuing this public health advisory to inform patients and health care professionals that the sponsor of Zelnorm (tegaserod maleate), Novartis Pharmaceuticals Corporation, has agreed to stop selling Zelnorm. Zelnorm is being taken off the market because a new safety analysis has found a higher chance of heart attack, stroke, and worsening heart chest pain that can become a heart attack in patients treated with Zelnorm compared to those treated with a sugar pill they thought was Zelnorm.

FDA announces the following, effective immediately:

* At FDA’s request, Novartis Pharmaceuticals Corporation has agreed to stop selling Zelnorm.
* Patients being treated with Zelnorm should contact their physician to discuss alternative treatments for their condition.
* Patients who are taking Zelnorm should seek emergency medical care right away if they experience severe chest pain, shortness of breath, dizziness, sudden onset of weakness or difficulty walking or talking or other symptoms of a heart attack or stroke.
* Physicians who prescribe Zelnorm should work with their patients and transition them to other therapies as appropriate to their symptoms and need.

Zelnorm is a prescription medication approved for short term treatment of women with irritable bowel syndrome with constipation and for patients younger than 65 years with chronic constipation. In late February and early March 2007, Novartis Pharmaceuticals gave FDA the results of new analyses of 29 clinical studies of Zelnorm for treatment of a variety of gastrointestinal tract conditions; the data from all the studies were combined to assess the chance of side effects on the heart and blood vessels. In each study, patients were assigned at random to either Zelnorm or a sugar pill they thought was Zelnorm. These 29 studies included 11,614 patients treated with Zelnorm and 7,031 treated with a sugar pill. The average age of patients in these studies was 43 years and most patients—88%--were women.

The number of patients who suffered a heart attack, stroke or severe heart chest pain that can turn into a heart attack was small. However, patients treated with Zelnorm had a higher chance of having any of these serious and life-threatening side effects than did those who were treated with a sugar pill. Thirteen patients treated with Zelnorm (0.1%) had serious and life-threatening cardiovascular side effects; among these, four patients had a heart attack (one died), six had a type of severe heart chest pain which can quickly turn into a heart attack, and three had a stroke. Among the patients taking the sugar pill, only one (or 0.01%) had symptoms suggesting the beginning of a stroke that went away without complication.

There may be patients for whom no other treatment options are available and in whom the benefits of Zelnorm treatment outweigh the chance of serious side effects. FDA will work with Novartis to allow access to Zelnorm for those patients through a special program.

FDA has also indicated to Novartis a willingness to consider limited re-introduction of Zelnorm at a later date if a population of patients can be identified in whom the benefits of the drug outweigh the risks. However, before FDA makes a decision about limited re-introduction, any proposed plan would be discussed at a public advisory committee meeting.