Angina Comprehensive: Biovail Reports Positive Phase III Clinical Trial Results for Graded Release Diltiazem -- G-99 -- In Chronic Stable Angina Pectoris.

Business Editors

TORONTO--(BUSINESS WIRE)--Oct. 29, 2002

-- G-99 dosed in the evening demonstrated a clinically significant improvement in morning exercise tolerance compared to the same dose given in the morning,

-- G-99, dosed in the evening, significantly increased exercise tolerance in patients with angina pectoris 24 hours after dosing (trough).

-- The side effect profile of G-99 was comparable to placebo even at the highest dose of 420mg.

Biovail Corporation (NYSE, TSX: BVF) today announced positive Phase III clinical trial results of the new graded release formulation of diltiazem hydrochloride (G-99) in chronic stable angina pectoris. The results of this study, in conjunction with an earlier hypertension study, confirm the therapeutic advantages of G-99.

G-99, an investigational new drug not yet approved by the U.S. Food and Drug Administration (FDA) is a calcium channel blocker seeking indications for the treatment of hypertension and angina. It is the first once daily graded release diltiazem formulation that uses a unique dissolution profile, in conjunction with evening dosing, to advance the efficacy of diltiazem therapy. A New Drug Application (NDA) for G-99 for the treatment of hypertension was filed with the FDA in August of 2001 and an approvable letter was received in June of 2002. Biovail anticipates final FDA approval and launch of this product to the trade by the end of the year.

Angina Phase III Study

This double blind, placebo-controlled Phase III clinical trial to evaluate the efficacy and safety of G-99 in the treatment of chronic stable angina has been recently completed. Patients who met qualification criteria were randomly assigned to evening doses of 180mg, 360mg or 420mg; or a morning dose of 360mg or placebo. The study design included a 2- to 3-week single blind, placebo, run-in period, followed by a 1-week double-blind titration period, and a 2-week double-blind maintenance period. Evening and morning treadmill stress tests were performed during the single blind, placebo run-in period to establish baseline values and were repeated at the end of the double blind period.

The primary measure of efficacy was change from baseline to final visit in total duration of exercise as measured by treadmill stress test during the trough period. The period of 6pm to 8pm was evaluated for 180mg, 360mg and 420mg evening doses of G-99 and placebo while 7am to 11am was evaluated for 360mg G-99 dosed in the morning and placebo. Total duration of exercise was defined as the total time a patient was able to exercise on the treadmill until the patient had to stop because of moderate angina. Moderate angina was defined as the severity of pain that would ordinarily cause a patient to stop exercising during normal everyday activity.

Key secondary variables included change from baseline to final visit in total duration of exercise during 7am to 11am; and change from baseline to final visit in time to onset of exercise induced angina and time to onset of exercise-induced myocardial ischemia at trough and at 7am to 11am.

In this study, all evening doses of G-99 showed a statistically significant and clinically meaningful increase in exercise tolerance compared to placebo at trough. In contrast, G-99 360mg dosed in the morning approached, but did not reach statistical significance, thus demonstrating the superior results of this unique formulation when dosed in the evening.

The analyses of the secondary variables further demonstrate the anti-angina benefits of evening dosing of G-99. Between 7am to 11am, the time period when cardiovascular events are most frequent and the incidence of angina and myocardial ischemia are the greatest, all evening doses of G-99 were statistically significantly different from placebo in total duration of exercise, in time to onset of angina and in time to onset of myocardial ischemia. Notably, the efficacy of G-99 when dosed in the evening was greater between 7am to 11am than between 6pm to 8pm for these key secondary variables. This demonstrates that the graded release formulation when dosed in the evening provides it optimal effect when it is most needed -- at the time period when the incidence of angina and myocardial ischemia is the greatest -- yet still provides 24 hour coverage at all doses. A similar pattern of efficacy was observed for G-99 in the treatment of essential hypertension.

Comparison of the efficacy of G-99 360mg pm and 360mg am further substantiate the advantages of evening dosing. During the period of 7am to 11am, evening administration of G-99 resulted in more than 2-fold greater efficacy for all key efficacy variables (total duration of exercise, time to onset of angina and time to onset of myocardial ischemia) than the identical dose administered in the morning.

G-99 was safe, well tolerated and produced and adverse event profile consistent with what has been previously described for G-99. Adverse events were generally mild to moderate in nature and comparable to placebo at the highest dose (420mg).

"The results of this study are exciting because the study answers several important questions," noted Dr. Stephen Glasser, lead study investigator and professor of epidemiology at the University of Minnesota, School of Public Health. "First, that significant greater efficacy is demonstrated in the early morning time period; second, the results show that evening dosing of G-99 demonstrates efficacy 24 hours after dosing; third, that there is a difference between dosing G-99 in the morning versus the evening, which is not evident with any other diltiazem preparation; and importantly, that the side effect profile of even the highest dose of G-99 was not different from placebo, supporting the long term impression that diltiazem is one of the safest drugs and safest calcium antagonists on the market. G-99 then represents a unique once a day therapy that is safe to titrate to maximum dose and through evening dosing, produces an advancement in diltiazem efficacy."

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.

For further information, please contact Ken Howling at 905-286-3000 or send inquiries to [e-mail].

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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.