Biovail Reports Clinical Trial Results

Business Wire, March 5, 2003

Business Editors/Health/Medical Writers

TORONTO--(BUSINESS WIRE)--March 5, 2003

Biovail Corporation (NYSE:BVF)(TSX:BVF)

-- Cardizem LA Phase IV results in African-American hypertensive patients

-- Buspirone Phase III results in patients with Generalized Anxiety Disorder

Biovail Corporation (NYSE:BVF)(TSX:BVF) announced today the positive Phase IV clinical trial results for Cardizem(R) LA in lowering blood pressure in African-Americans, as compared to amlodipine. The reduction was measured using ambulatory blood pressure monitoring (ABPM). Cardizem(R) LA is a new graded release formulation of diltiazem HCl for the treatment of hypertension (high blood pressure).

Compared to amlodipine, Cardizem(R) LA demonstrated better diastolic blood pressure (DBP) control both in the early morning period after awakening and between 6AM to 12 noon. Cardizem(R) LA also demonstrated DBP control over a 24-hour period that was comparable to amlodipine. Cardizem(R) LA showed superior reductions in rate-pressure product, an index of myocardial oxygen demand, in the early morning period after awakening, between 6AM to 12 noon, and over 24-hours. These results are consistent with a similar study comparing Cardizem(R) LA to ramipril in an earlier hypertension trial and again confirm the therapeutic advantages of Cardizem(R) LA.

The U.S. Food and Drug Administration (FDA) recently approved Cardizem(R) LA for commercialization. Cardizem(R) LA is specifically labeled to allow administration in the morning or the evening. With evening administration, clinical trials have shown that the graded release technology results in increased reduction of blood pressure in the early morning hours when heart rate and blood pressure rise and when the incidence of cardiovascular events peaks.

Comparator Phase IV Study Design:

Cardizem(R) LA versus Amlodipine in African-American Patients with Stage I and II Hypertension

This Phase IV clinical study evaluating the safety and efficacy of Cardizem(R) LA versus amlodipine in Stage I and II hypertensive African-American patients has been successfully completed. Patients were eligible for randomization if their seated office cuff DBP was between 90 - 109 mm/Hg at two consecutive visits and their daytime DBP as measured by ABPM was between 85 - 109 mm/Hg. Patients were excluded if their office cuff seated systolic blood pressure (SBP) was greater than 180mm/Hg.

After randomization, the starting dose of Cardizem(R) LA was 360mg once-daily in the evening while that for amlodipine was 5mg once-daily in the morning. Patients were titrated up to Cardizem(R) LA 540mg or amlodipine 10mg after six weeks, if their office seated DBP was greater than or equal to 85mm/Hg or their office seated SBP was greater than or equal to 130mm/Hg. Patients were maintained on their final dose of Cardizem(R) LA or amlodipine for an additional six weeks for total treatment duration of 12 weeks. An ABPM was performed at study end.

The primary efficacy variable was the change in baseline to final visit in mean DBP as measured by ABPM during the first four hours of awakening. This is the period that coincides with the time of day hypertensive patients are at highest risk for cardiovascular events such as heart attack and stroke. Secondary measures of efficacy included DBP as measured by ABPM between 6AM and 12 noon and over 24-hours. Rate-pressure product (heart rate x systolic blood pressure), an index of myocardial oxygen consumption, the most important indicator of load to the heart, was measured over all time intervals. SBP changes were also measured over all intervals.

There was a highly statistically significant and clinically meaningful difference in DBP reduction favoring Cardizem(R) LA during the first four hours of awakening (the primary variable) and between 6AM and 12 noon. DBP reductions were comparable to amlodipine over 24-hours. Reductions in rate-pressure product in favor of Cardizem(R) LA were highly statistically significant over all time intervals measured. Reductions in rate-pressure product are important because studies have shown that episodes of silent myocardial ischemia are preceded by an increase in the rate-pressure product.

The overall incidence of adverse events was generally comparable between the two treatments groups. The types of adverse events were consistent with what has been observed for each product in previous clinical trials.

Biovail also announced today that the Phase III clinical trial comparing once-daily Buspirone to placebo in patients with Generalized Anxiety Disorder (GAD) has been completed and the results evaluated. After eight weeks of treatment, the primary efficacy variable, change from baseline to final visit in the Hamilton Anxiety Rating Scale (HAM-A), approached, but did not achieve statistical significance compared to placebo. All secondary variables favored active drug, but were not statistically significantly different compared to placebo with the exception of clinical global impression of change (CGI-C). In light of these unfavorable results, Biovail plans to discontinue development of this product.