Data Presented At American Heart Association Show Risk of Mild Cardiac Valve Abnormalities Among Long-Term Redux Patients to be Low.

LEXINGTON, Mass.--(BW HealthWire)--Nov. 10, 1998--

Findings Suggest Use Of Concomitant Drugs And High Blood Pressure

May Increase Association With Positive Cardiac Echo Findings

Results of a blinded, control group, multi-center clinical study presented today at the Scientific Sessions of the American Heart Association show a low overall incidence of FDA-defined cardiac valve abnormalities among patients who took the anti-obesity medication, Redux, for three months or longer when compared to individuals who had not taken Redux. No severe and very few moderate cardiac valve abnormalities were found in either Redux patients or non-Redux subjects.

The incidence of cardiac valve abnormalities among Redux patients reported in this study, although statistically significant, was far less than some previously reported estimates. In addition, findings from the study suggest that elevated blood pressure at the time that echocardiograms were taken among these patients, as well as the concomitant use of drugs with monoamine oxidase inhibitory properties, which were contraindicated with the use of Redux, increased the incidence of cardiac valve abnormalities. Additional findings suggest that the greater the time off Redux, the less likely patients were to show valvular abnormalities. These findings are being further evaluated.

The average duration of Redux use among all Redux patients in this study was seven months. The study, funded by Interneuron Pharmaceuticals, Inc. (Nasdaq: IPIC), was designed to evaluate the impact of long-term use of Redux alone upon the incidence of cardiac valve disease as defined by the U.S. FDA. However, market research indicates that approximately 86 percent of patients took Redux for 90 days or less and approximately 6.5 percent took Redux for six months or more. Findings from this study were presented by Bruce Shively, M.D., F.A.C.C. from the Oregon Health Sciences University.

Redux was a prescription anti-obesity drug withdrawn from the market in September 1997 by Interneuron and Wyeth-Ayerst Laboratories, a division of American Home Products Corporation.

Conducted at 26 clinical sites across the country, the study included a total of 412 patients. Of these, 350 patients were enrolled as matched pairs, half of whom had taken Redux and half of whom had not taken Redux and were matched with a Redux patient based on age, sex and body mass index (BMI). Patients in both groups had not taken other weight loss medications for the previous five years. The primary outcome measurement of the study was the incidence of cardiac valve abnormalities, as evaluated by echocardiography. Readings of echocardiograms were performed on a blinded basis by three independent readers.

Analyses were conducted based on echocardiographic data from the total patient population entered into the study and also from the core group, which included only the matched pairs. Cardiac valve disease was defined as mild or greater aortic valve regurgitation and/or moderate or greater mitral valve regurgitation. Previous reports had estimated rates of cardiac valve insufficiences among anorexigen-treated patients of up to 30 percent.

Among all study participants, 1.4 percent of Redux patients and 0.5 percent of non-treated patients (p=.63) met the FDA's definition of mitral valve regurgitation. Among the core group of matched pairs, 1.7 percent of Redux patients and 0.6 percent of non-treated controls (p=.32) met this definition.

With respect to aortic valve regurgitation, in all patients, 5.9 percent of Redux patients and 2.1 percent of non-treated patients (p=.08) met the FDA's definition. Among the core group of matched pairs, 6.3 percent of Redux patients and 2.3 percent of non-treated controls (p=.07) met this definition.

For all patients with either aortic or mitral valve regurgitation meeting FDA criteria only, the incidence was 2.6 percent for controls and 7.3 percent for the Redux patients (p=.04). When analyzed for valvular insufficiency of any degree including trace, there was an increased incidence in the Redux group when compared to the untreated control group for the aortic valve (p=.04) but not the mitral valve (p=.28).

When potentially confounding factors were considered, such as use of concomitant monoamine oxidase inhibitors (such as estrogens and thyroid hormone replacements), and the patients' blood pressures at the time of their echocardiograms, the difference in the incidence of valvular insufficiency between Redux and non Redux treated patients became non-significant. For example, when patients who were exposed to concomitant drugs possessing monamine oxidase inhibitory properties were excluded from the analysis, 3 percent of control group patients met FDA-criteria for aortic and mitral valve regurgitation as compared with 4 percent in the Redux group (p=not significant).

"The data from this study was gathered to contribute to our understanding of the clinical implications of previous use of Redux," said Glenn L. Cooper, M.D., president and chief executive officer of Interneuron. "The data show a low overall association between Redux and cardiac valve abnormalities, when taken alone as indicated on its label."

As previously announced, a U.S. District Court has preliminarily approved a formal settlement agreement with regard to Interneuron's Redux product liability litigation and has issued stays halting litigation against Interneuron in federal and state courts. The formal settlement will not become final until approved by the Court and the time for filing appeals has passed or all appeals have been exhausted.

Interneuron Pharmaceuticals and its majority-owned subsidiary, Intercardia, Inc. (Nasdaq:ITRC) are engaged in the development and commercialization of a portfolio of products and product candidates for central nervous system, cardiovascular and other disorders, including multiple compounds in late-stage clinical development.

Except for the descriptions of historical facts contained herein, this press release contains forward-looking statements that involve risks and uncertainties as detailed from time to time in the Company's filings under the Securities Act of 1933 and the Securities Exchange Act of 1934, including in particular, risks relating to the withdrawal of Redux and Redux-related litigation, including risk relating to the finalization of the proposed related settlement; uncertainties relating to regulatory approvals and clinical trials; product liability; the need for additional funds; the early stage of products under development; risks relating to product launches and managing growth; government regulation, patent risks, dependence on third parties and competition.