Company Overview

Biovail Corporation International has developed a second generation controlled released once-daily Diltiazem formulation (Diltiazem OD ER Tiazac) for the management of hypertension and angina. It incorporates an advanced drug delivery technology which addresses the major limitations of currently marketed first generation once-daily diltiazem products.

Diltiazem has grown to be one of the leading compounds in the world since its introduction in 1982. Worldwide sales in 1996 were in excess of $1.7 billion (US).

The calcium channel blocker market has grown to reach annual sales of $3.5 billion in the United States in 1996 through the introduction of a number of highly effective anti-hypertensives, and through the successful re-design of their delivery systems. The introduction of verapamil, nifedipine and diltiazem in the early 1980's provided several highly effective and well tolerated products for the management of hypertension. Since them, they have all been re-engineered to incorporate various types of drug delivery systems which have greatly enhanced their therapeutic characteristics and marketability. The dominant products today are once-daily nifedipine, diltiazem and verapamil. The growth of these compounds can be expected to continue into the future as their effectiveness and safety are further enhanced through the use of increasingly sophisticated and reliable drug delivery technologies.

Tiazac's unique profile makes it an ideal compound for the treatment of both hypertension and angina. Tiazac incorporates an advanced drug delivery technology which addresses the major limitations of currently marketed diltiazem products.

There is a growing awareness and acceptance by physicians of once-daily diltiazem compounds as safe and effective, first-line treatment for mild to moderate hypertension. Also, more and more, prescribers are switching angina patients from immediate-release diltiazem products to once-daily products.

Although there are a number of once-daily diltiazem products, many of the currently marketed products are available in a limited number of strengths, and not all once- daily diltiazem products are approved for both hypertension and angina. Tiazac has a number of key competitive advantages over existing once-daily diltiazem products on the market.

Tiazac Key Advantages

• Tiazac will be approved for the treatment of both

hypertension and angina, whereas many competing once- daily diltiazem products are only approved for the treatment of angina.

• The widest dosage range for greater dose flexibility and

titration, which prescribers consider key, especially in the treatment of hypertension.

• An incidence of side-effects comparable to placebo at all

dosing levels.

• A more compact capsule size which is on average 40%

smaller than equivalent does of competing products. Tiazac is the only once-daily product that allows the use of a single capsule for doses ranging from 120mg to 360mg, thus providing enhanced convenience, improved compliance, and optimal dosing flexibility.

• Tiazac's unique pharmacokinetic profile is associated with

higher diltiazem blood levels during the day, when blood pressure is at its highest.

• Both in the treatment of angina and hypertension, Tiazac's

clinical efficacy is maintained for 24 hours.

• Tiazac can be taken with or without food
• The patented technology and unique formulation provide

an effective barrier to generic duplication.

• Diltiazem's proven history of safety and efficacy.

In summary, Tiazac's unique profile allows prescribers to target both hypertensive and angina patients, and also patients whose profile previously led physicians to prescribe other calcium channel blockers. The market share of once- aily diltiazem products approved for both hypertension and angina is expected to continue to grow substantially. Tiazac's key competitive advantages position it to gain rapid penetration of both the anti-hypertensive and the anginal market.

Diltiazem SR OD ER (Tiazac) received FDA approval in

• Tiazac is marketed in the United States by Forest

Laboratories, Inc. In Canada, Tiazac is marketed by Crystal Corporation, an operating division of Biovail Corporation International. Biovail Diltiazem OD ER received approval in the United Kingdom in April 1996. Additional European approvals are expected shortly. Biovail's Diltiazem OD ER is licensed to DuPont Merck for the United Kingdom and Ireland, to Pierre Fabre S. A. for France, to Alter for Spain, to Zambon B. V. for the Netherlands, and to Ratiopharm and Heumann Pharma for Germany. Other international licensing agreements will be announced shortly.

CORPORATE PROFILE

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

The Company's strategy is to control all facets of its research and development efforts, including formulation development, clinical studies, regulatory submissions and manufacturing. This integrated approach enables the Company to enter into licensing agreements with major pharmaceutical partners seeking drug delivery expertise, coupled with operational synergies, flexibility and cost efficiencies.

Biovail applies its oral drug delivery technologies to drug compounds free of patent protection, in order to develop novel formulations which improve on conventional dosage forms, or to produce generic versions of branded controlled-release products to provide a price advantage. The Company focuses on the development of products for the treatment of chronic diseases, including cardiovascular diseases, arthritis, bronchial conditions and pain management.

HIGHLIGHTS

• Growing Market for Oral Controlled-release Products.

The oral controlled-release pharmaceutical market is currently growing in excess of 30% annually, offering significant opportunities for Biovail and its licensing partners. Of more than 40 products using controlled-release technology, 20 products are currently devoid of patent protection. U. S. sales of controlled-release products exceeds $6 billion. In addition, Biovail is one of a limited number of companies with a successful track record of developing and gaining approval for oral controlled-release pharmaceutical products.

• Flexible Proprietary Technology. The Biovail controlled-

release technologies allow pharmaceutical compounds to be administered once-daily, releasing them in predetermined and controlled fashion over a 24 hour period. The result typically is enhanced therapeutic effectiveness, reduced side effects and improved patient compliance. Biovail has 5 different technology platforms. These proven technologies are highly flexible, providing a broad range of release profiles that can be tailored to the physical, chemical and clinical properties of a given drug compound.

• Numerous Products Successfully Developed. Biovail has

successfully developed and licensed 12 products which are currently marketed by major pharmaceutical companies worldwide. Important products include Tiazac (Diltiazem OD ER), licensed both in the U. S. and a growing number of European countries, once-daily formulations of ketoprofen, marketed under the brand name Oruvail by Wyeth-Ayerst Laboratories in the U. S. and under several brand names by Phone-Poulenc Rorer internationally, Theo-24 (thaophylline) marketed by UCB, and Norpace CR (disopryamide) by G. D. Searle.

• Promising Product Pipeline. Biovail has a strong product

pipeline with numerous products under development:

including both NDA (branded) and ANDA (generic) controlled-release products.

RECENT EVENTS

• In 1995 Biovail received approval from the U. S. Food and

Drug Administration to market Tiazac in the United States. This once-daily extended release formulation of Diltiazem is used in the treatment of both hypertension and angina, and competes in the $3.2 billion U. S. calcium channel blocker market; it has the potential to be a $100-200 million branded product. Biovail's Diltiazem OD ER was approved in the United Kingdom in April 1996. Additional European approvals, and HPB approval in Canada is expected shortly.

• To support the product development effort, Biovail has

recently established a new 24, 000 square foot R&D facility in West Toronto, Ontario. The West Toronto center supports the Company's expanded R&D activities, which has produced a substantial product pipeline. The R&D group works closely with the new R&D Division in Puerto Rico.

• To support Biovail's marketing efforts in Canada, the

company established Crystaal Corporation, an operating division of BCI, headquartered in Montreal, Quebec. Crystaal Corporation is dedicated to providing high quality, cost effective pharmaceuticals to Canadian health care professionals, patients and third party payers. Crystaal Corporation's portfolio includes products manufactured and/or licensed by Biovail, as well as products in-licensed from external sources. Crystaal's strategy is to source and develop worldwide in-licensing agreements for original and/or multisource products, and to form strategic joint ventures and partnerships providing access to novel pharmaceutical compounds.

• In 1995 Biovail acquired the know-how and the R&D and

manufacturing resources of Puerto Rico based Galephar P. R., Inc., a drug delivery company specializing in the development of controlled-release products Galephar was the co-developer of Biovail's Tiazac, its once-daily Diltiazem product.

• In 1995 Biovail received approval by the FDA for Oruvail

100mg and 150mg extended release capsules. Market clearance for these two dosing strengths greatly increases the dosing flexibility of Oruvail 200mg extended release capsules. The addition of these two new longer dosages permits the use of Oruvail in elderly and renally impaired patients, a population segment where the product was previously contraindicated. Oruvail was approved in September 1993, and launched by the Company's marketing partner Wyech-Ayerst Laboratories in October, 1993. Oruvail is used to treat osteoarthritis and rheumatoid arthritis, conditions affecting a total of 18 million Americans. The market for these indications exceeds $2 billion and provides Oruvail with an estimated market potential of U. S. $200-300 million. 1995 sales were U. S. $150 million.

• Recent Licensing Agreements. Biovail has recently

entered into a number of licensing agreements. Diltiazem OD ER (Tiazac) received FDA approval in 1995. Tiazac is marketed in the United States by Forest Laboratories, Inc. Biovail's Diltiazem OD ER received approval in the United Kingdom in April 1996. Additional European approvals are expected shortly. Biovail's Diltiazem OD ER is licensed to DuPont Merck for the United Kingdom and Ireland, to Pierre Fabre S. A. for France, to Alter for Spain, to Zambon B. V. for the Netherlands, and to Ratiopharm and Heumann Pharma for Germany.

Company Information

Additional Details

Legal Name: Biovail Corporation

Contacts

Services

• Biotechnology

Products

• Antilipemic Agents
• Beta-timelets - Propranolol Sr Od

  used for hypertension and angina, beta blocking agent

• Calcium Antagonists
• Dilitiazem Sr Bid

  used for angina and hypertension, twice-daily calcium channel blocker

• Diltiazem Cd

  used for angina and hypertension, once-daily calcium channel blocker

• Diltiazem Od
• Elanten Long - Isosorbide-5-mononitrate Sr Od

  used for angina, vasodilator

• Gastro-timelets Gastromax - Metoclopramide Sr Od

  used for gastric reflus, GI tract mobility modifier

• Isoket Retard - Isosorbide Dinitrate Sr Od

  used for angina, vasodilator

• Nifedipine Xl

  used for angina and hypertension, calcium channel blocker

• Norpace - Disopyramide Sr Bid

  used for arrhythmias, type 2 antiarrhythmic

• Novagent - Ibuprofen Sr Od

  used for arthritis, non-steroidal anti-inflammatory

• Oruvail - Ketoprofen Sr Od

  used for arthritis, non-steroidal anti-inflammatory

• Pain Management
• Pentoxifylline Sr

  used for peripheral chronic, occlusive arterial disease

• Regenon Retard, Diethylpropion Sr Od

  used for anti-obesity therapy, symaphomimetic agent

• Sirdalud Cr - Tizanidine Sr Od

  used for muscle relaxant

• Synthetic Retinoids
• Theo-24 - Theophylline Sr Od

  used for asthma and bronchitis, xanthine bronchodilator

• Tiamon Mono - Dihydrocodeine Sr Od

  used for analgesic, opioid derivative

• Verapamil Sr Od Capsules

  used for hypertension and arrhythmias, calcium channel blocker

NAICS Categories

• 325410 Pharmaceutical and Medicine Manufacturing

Additional Information