Biovail Reports Positive Cardizem XL Clinical Results.

Business & Health/Medical Editors

TORONTO--(BW HealthWire)--July 24, 2001

Biovail Corporation (NYSE:BVF)(TSE:BVF)

-- Combination of unique Cardizem(r) XL delivery profile and nighttime dosing
demonstrates clinically significant improvement over placebo and morning dosing


-- Innovative formulation addresses circadian variation in blood pressure with
optimal bioavailability characteristics not duplicated by competitive products

-- Clinically significant reduction in diastolic and systolic blood pressures
between 4 a.m. and 12 noon

-- Highest dose (540 mg) particularly effective and very well tolerated

Biovail Corporation (NYSE:BVF)(TSE:BVF) today announced dose related positive efficacy results with all four doses of Cardizem(r) XL in the targeted population of patients with moderate to severe hypertension. This innovative study is the first successful study comparing the efficacy and safety of administering the same dose of the same antihypertensive agent in the morning versus administration at bedtime. Cardizem(r) XL 360 mg dosed at night produced a highly significant and clinically meaningful reduction in diastolic blood pressure (DBP) and systolic blood pressure (SBP) between 4 a.m. and 12 noon compared to equivalent morning dosing. The study also demonstrated that higher nighttime dosing (540 mg) achieved clinically significant reductions in DBP and SBP and was very well tolerated.

Unlike other competitive products, Cardizem(r) XL is the first once-daily graded release diltiazem formulation that uses a unique dissolution profile, in conjunction with nighttime dosing, to address the body's typical 24 hour circadian variation in blood pressure. This innovative formulation has been designed to achieve maximum drug levels between 6 a.m. and 12 noon without compromising its bioavailability characteristics. The science of treating diseases that follow these circadian patterns is known as "chronotherapeutics" and is a well established practice in medicine for the management of certain medical conditions including asthma, sleep, gastric and peptic ulcer diseases, arthritis and cardiovascular disease.

There is a significant amount of clinical data that clearly shows that patients with hypertension and angina are at the greatest risk of adverse cardiac events, such as stroke or heart attack, between the hours of 6 a.m. and 12 noon. Peak concentrations of Cardizem(r) XL are delivered in the early waking hours when blood pressure and heart rate are rising (accelerated phase) at their highest rate.

"The importance of these results is that they give clinicians flexibility in administering diltiazem to their hypertensive patients," said Michael A. Weber, MD, the Dean of medical research at the State University of New York and the immediate past President of The American Society of Hypertension. "Many physicians believe that strokes, heart attacks and other cardiovascular events are most likely to occur during the morning hours, and so would like to prescribe blood pressure medicines that have their greatest effects at that time of day."

"The research results just released by Biovail show that their diltiazem product, Cardizem(r) XL when given the evening before is more effective at controlling critical morning blood pressures than when given at the more traditional breakfast time," he continued. "Indeed, this innovative clinical trial has demonstrated that varying the time at which this unique blood pressure formulation is taken can produce differences in effects that are potentially of strong clinical importance."

Weber commented further: "Two major international clinical trials that finished during the last couple of years, Syst-Eur and HOPE, dosed their principal cardiovascular drugs at night and reported significant survival benefits as well as reductions in serious events like strokes and heart attacks. Although the just completed Biovail study focused mainly on its blood pressure effects, it is important to remember that another recently completed study with diltiazem, known as the NORDIL trial, showed that diltiazem provided protection against strokes and other complications of hypertension that was at least as good as and in some cases better than that found with other agents."

Weber concluded, "It is important to be careful in evaluating the results of a large new trial, but I think it is already evident that the results announced by Biovail will be very helpful in allowing doctors to be more selective in controlling blood pressure in their patients. I was also pleased to note that the maximum Cardizem(r) XL dose of 540 mg, which was particularly effective in reducing blood pressure, was so well tolerated by the patients."

Overall Study Design and Plan

This was a double blind, randomized, parallel-group, dose response, placebo-controlled, multicenter study to assess the efficacy and safety of four PM doses of Cardizem(r) XL (120 mg, 240 mg, 360 mg and 540 mg) with one AM dose of Cardizem(r) XL (360 mg). Blood pressure changes were measured by ambulatory blood pressure monitoring (ABPM) at specified intervals as well as by office cuff sphygmomanometer at all clinic visits.

A total of 462 patients from 18 to 70 years of age with moderate to severe hypertension were planned for study enrollment. Qualifying patients were randomized to placebo, and Cardizem(r) XL doses of 120 mg PM, 240 mg PM, 360 mg PM, 360 mg AM and 540 mg PM. Patients randomized to the 540 mg group were started initially on 360 mg for 1 week and then force-titrated in a blinded fashion to 540 mg. Patients randomized to placebo and Cardizem(r) XL doses of 120 mg, 240 mg, or 360 mg did not require titration during the study, but rather were started on their respective daily doses. Patients received maintenance treatment for an additional 6 weeks. A 36-hour ABPM was performed at the end of the run-in period (baseline data) and repeated at the end of the active treatment period (final visit data). Patients were evaluated at weekly intervals during the run-in and titration periods and at 2-week intervals during the active treatment period following titration.

Biovail Corporation is an international full-service pharmaceutical company, engaged in the formulation, clinical testing, registration, manufacture, sale and promotion of pharmaceutical products utilizing advanced drug delivery technologies.

"Safe Harbor" statement under the Private Securities Litigation Reform Act of 1995. To the extent any statements made in this release contain information that is not historical, these statements are essentially forward looking and are subject to risks and uncertainties, including the difficulty of predicting FDA approvals, acceptance and demand for new pharmaceutical products, the impact of competitive products and pricing, new product development and launch, reliance on key strategic alliances, availability of raw materials, the regulatory environment, fluctuations in operating results and other risks detailed from time to time in the company's filings with the Securities and Exchange Commission.